The standardisation of terminology of lower urinary tract function: Report from the standardistation sub-committee of the International Continence Society.

The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society.

Background Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. Methods In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. Results In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P = 0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P = 0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. Conclusions The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

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Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society.

Objective: To determine the ability of measurements of bone density in women to predict later fractures. Design: Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. Subjects: Eleven separate study populations with about 90000 person years of observation time and over 2000 fractures. Main outcome measures: Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. Results: All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. Conclusions: Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density. Key messages Measuring bone mineral density has been suggested as a method of identifying individuals at high risk of fracture in a preventive context Our meta-analysis of prospective studies showed that all studies measuring bone density at any site had similar predictive ability for a decrease of 1 SD in bone density except for measurements at hip and spine, which have better predictive ability for fractures in hip and spine respectively Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease Although bone mineral density measurements can predict fracture risk, they cannot identify individuals who will have a fracture, and a screening programme for osteoporosis cannot be recommended

Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures

25. Multiple Imputation for Nonresponse in Surveys. By D. B. Rubin. ISBN 0 471 08705 X. Wiley, Chichester, 1987. 258 pp. £30.25.

Multiple Imputation for Nonresponse in Surveys

OBJECTIVES: Delirium (or acute confusional state) affects 35% to 65% of patients after hip-fracture repair, and has been independently associated with poor functional recovery. We performed a randomized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture. DESIGN: Prospective, randomized, blinded. SETTING: Inpatient academic tertiary medical center. PARTICIPANTS: 126 consenting patients 65 and older (mean age 79 6 8 years, 79% women) admitted emergently for surgical repair of hip fracture. MEASUREMENTS: Detailed assessment through interviews with patients and designated proxies and review of medical records was performed at enrollment to ascertain prefracture status. Subjects were then randomized to proactive geriatrics consultation, which began preoperatively or within 24 hours of surgery, or “usual care.” A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol. To ascertain study outcomes, all subjects underwent daily, blinded interviews for the duration of their hospitalization, including the Mini-Mental State Examination (MMSE), the Delirium Symptom Interview (DSI), and the Memorial Delirium Assessment Scale (MDAS). Delirium was diagnosed using the Confusion Assessment Method (CAM) algorithm. RESULTS: The 62 patients randomized to geriatrics consultation were not significantly different ( P . .1) from the 64 usual-care patients in terms of age, gender, prefracture dementia, comorbidity, type of hip fracture, or type of surgical repair. Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively. A mean of 10 recommendations were made throughout the duration of the hospitalization, with 77% adherence by the orthopedics team. Delirium occurred in 20 ⁄62 (32%) intervention patients, versus 32 ⁄ 64 (50%) usual-care patients ( P 5 .04), representing a relative risk of 0.64 (95% confidence interval (CI) 5 0.37‐0.98) for the consultation group. One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group. There was an even greater reduction in cases of severe delirium, occurring in 7⁄60 (12%) of intervention patients and 18 ⁄62 (29%) of usual-care patients, with a relative risk of 0.40 (95% CI 5 0.18‐0.89). Despite this reduction in delirium, length of stay did not significantly differ between intervention and usual-care groups (median 6 interquartile range 5 5 6 2 days in both groups), likely because protocols and pathways predetermined length of stay. In subgroup analyses, geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living (ADL) functional impairment. CONCLUSIONS: Proactive geriatrics consultation was successfully implemented with good adherence after hipfracture repair. Geriatrics consultation reduced delirium by over one-third, and reduced severe delirium by over one-half. Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients. J Am Geriatr Soc 49:516‐522, 2001.

Reducing delirium after hip fracture: A randomized trial

OBJECTIVE: To evaluate the role of delirium in the natural history of functional recovery after hip fracture surgery, independent of prefracture status.

DESIGN: Prospective cohort study.

SETTING: Orthopedic surgery service at a large academic tertiary hospital, with follow-up extending into rehabilitation hospitals, nursing homes, and the community.

PARTICIPANTS: One hundred twenty-six consenting subjects older than 65 years (mean age 79 ± 8 years, 79% women) admitted emergently for surgical repair of hip fracture.

MEASUREMENTS: Detailed assessment at enrollment to ascertain prefracture status through interviews with the patient and designated proxy and review of the medical record. Interviews included administration of standardized instruments (Activities of Daily Living (ADL) Scale, Blessed Dementia Rating Scale, Delirium Symptom Interview) and assessment of ambulation, and prefracture living situation. Medical comorbidity, the nature of the hip fracture, and the surgical repair were obtained from the medical record. All subjects underwent daily interviews for the duration of the hospitalization, including the Mini-Mental State Examination and Delirium Symptom Interview, and delirium was diagnosed using the Confusion Assessment Methods algorithm. Patients and proxies were recontacted 1 and 6 months after fracture, and underwent interviews similar to those at enrollment to determine death, persistent delirium, decline in ADL function, decline in ambulation, or new nursing home placement.

RESULTS: Delirium occurred in 52/126 (41%) of patients, and persisted in 20/52 (39%) at hospital discharge, 15/52 (32%) at 1 month, and 3/52 (6%) at 6 months. Patients aged 80 years or older, and those with prefracture cognitive impairment, ADL functional impairment, and high medical comorbidity were more likely to develop delirium. However, after adjusting for these factors, delirium was still significantly associated with outcomes indicative of poor functional recovery 1 month after hip fracture: ADL decline (odds ratio (OR) = 2.6; 95% confidence interval (95% CI), 1.1- 6.1), decline in ambulation (OR = 2.6; 95% CI, 1.03–6.5), and death or new nursing home placement (OR = 3.0; 95% CI, 1.1–8.4). Patients whose delirium persisted at 1 month had worse outcomes than those whose delirium had resolved.

CONCLUSIONS: Delirium is common, persistent, and independently associated with poor functional recovery 1 month after hip fracture even after adjusting for prefracture frailty. Further research is necessary to identify the mechanisms by which delirium contributes to poor functional recovery, and to determine whether interventions designed to prevent or reduce delirium can improve recovery after hip fracture. J Am Geriatr Soc 48:618–624, 2000.

Delirium Is Independently Associated with Poor Functional Recovery After Hip Fracture

Objective. —To determine the relative importance of fall characteristics, body habitus, and femoral bone mineral density (BMD) in predicting hip fracture in community-dwelling elderly. Design. —Prospective case-control study. Setting. —Community-based academic hospital. Participants. —A total of 149 ambulatory, community-dwelling fallers (126 women, 23 men) aged 65 years and older, including 72 case patients (fallers with hip fracture) and 77 control fallers (fallers with no hip fracture). Main Outcome Measures. —Fall characteristics, body habitus, femoral BMD. Results. —Significant and independent risk factors for hip fracture in both sexes were direction of the fall (adjusted odds ratio [OR], 5.7; 95% confidence interval [Cl], 2.3 to 14.0;P Conclusions. —We conclude that among elderly fallers—in most of whom hip BMD is already less than the fracture threshold—fall characteristics and body habitus are important risk factors for hip fracture and touch on a domain entirely missed by knowledge of BMD. These data suggest new targets for preventive therapy. In addition to the maintenance of bone density, reductions in fall severity (eg, by use of trochanteric padding or enhancement of muscle strength) may provide additional strategies for prevention of hip fracture in this age group. (JAMA. 1994;271:128-133)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=362083&pdfFileName=jama_271_2_029.pdf

Fall severity and bone mineral density as risk factors for hip fracture in ambulatory elderly.

Little is known about the causes of urinary incontinence in institutionalized elderly people, despite the fact that $8 billion is annually devoted to diapering those afflicted. We have identified a specific physiological abnormality— detrusor hyperactivity with impaired contractile function (DHIC)—that, although previously unrecognized, is the second most common (33%) cause of incontinence in this setting. Detrusor hyperactivity with impaired contractile function is a distinct physiological subset of detrusor hyperreflexia and presents with a seemingly paradoxical set of findings: the bladder is overactive but empties ineffectively. This impaired emptying is due to diminished detrusor contractile function and is associated with bladder trabeculation, a slow velocity of bladder contraction, little detrusor reserve power, and a significant amount of residual urine. Aside from its high prevalence, the importance of DHIC is that it may present as urinary retention, may closely mimic prostatic outlet obstruction, may explain why past therapeutic trials for detrusor hyperreflexia have failed, and may necessitate a change in the current nosology of bladder dysfunction. Furthermore, DHIC may represent a more advanced stage in the natural history of detrusor hyperreflexia, a stage characterized by deterioration of detrusor contractile efficiency. Thus, this previously unrecognized cause of incontinence in the elderly is common and raises several important issues. (JAMA1987;257:3076-3081)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=366489&pdfFileName=jama_257_22_024.pdf

Detrusor Hyperactivity With Impaired Contractile Function: An Unrecognized but Common Cause of Incontinence in Elderly Patients

Although 1 million institutionalized elderly persons have urinary incontinence, little is known about the causes of this problem. We conducted clinical and physiologic studies to determine the causes of established incontinence in a representative sample of 605 institutionalized elderly persons (mean age, 89 years), of whom 40 percent were chronically incontinent of urine. Detailed urodynamic studies in 94 of the 245 incontinent patients (77 women and 17 men; 38 percent) showed that detrusor overactivity was the predominant cause in 61 percent, with concomitant impaired detrusor contractility present in half these patients. Other causes among women were stress incontinence (21 percent), underactive detrusor (8 percent), and outlet obstruction (4 percent). Among the relatively few men in this sample, outlet obstruction accounted for 29 percent of the cases. In 35 percent of the patients, at least two coexisting probable causes of incontinence were identified. Diagnoses among patients with impaired...

Neil M. Resnick

Papers

Reducing delirium after hip fracture: A randomized trial

Delirium Is Independently Associated with Poor Functional Recovery After Hip Fracture

Fall severity and bone mineral density as risk factors for hip fracture in ambulatory elderly.

Detrusor Hyperactivity With Impaired Contractile Function: An Unrecognized but Common Cause of Incontinence in Elderly Patients

The pathophysiology of urinary incontinence among institutionalized elderly persons.