Renal insufficiency as an independent predictor of mortality among women with heart failure

OBJECTIVES: We sought to explore the association between renal insufficiency and mortality among women with heart failure (HF) and to evaluate this risk by the presence of preserved or depressed systolic function. BACKGROUND: Although HF is common in older women, little is known about their risk factors for mortality. METHODS: This prospective cohort study retrospectively analyzed data from the Heart and Estrogen/progestin Replacement Study (HERS). Of the 2,763 women in HERS, 702 had HF. Renal function was categorized as creatinine clearance (CrCl) >60 ml/min, 40 to 60 ml/min, and <40 ml/min. We used proportional hazards models to evaluate the association between renal insufficiency and mortality. RESULTS: Over a mean 5.8 years, 228 women with HF died (32%). Renal insufficiency was strongly associated with mortality, even after adjustment for co-morbid conditions, systolic function, and medications (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.09 to 2.16 for CrCl 40 to 60 ml/min; adjusted HR 2.40, 95% CI 1.60 to 3.62 for CrCl <40 ml/min). Preserved or depressed systolic function did not modify the association between renal insufficiency and mortality risk, but the use of angiotensin-converting enzyme (ACE) inhibitors did modify this risk (ACE users: adjusted HR = 0.9, 95% CI 0.6 to 1.6; ACE nonusers: adjusted HR 2.1, 95% CI 1.3 to 3.2; p = 0.02 for interaction). Compared with other risk factors for mortality, renal insufficiency had the highest population attributable risk (27%). CONCLUSIONS: Renal insufficiency was a major predictor of mortality among women with HF and preserved or depressed systolic function. This risk was attenuated by the use of ACE inhibitors.     

Raloxifene,conjugated oestrogen and endothelial function in postmenopausal women

OBJECTIVES: To study the long-term effects of raloxifene, a potential designer oestrogen, and oestrogen monotherapy on endothelial function in healthy postmenopausal women. DESIGN: A 2-year double-blind, randomized and placebo-controlled study in an Academic Medical Center. Fifty-six hysterectomized but otherwise healthy postmenopausal women randomly received raloxifene hydrochloride 60 mg day-1 (n = 15) or 150 mg day-1 (n = 13), conjugated equine oestrogen (CEE) 0.625 mg day-1 (n = 15), or placebo (n = 13). MAIN OUTCOME MEASURES: Endothelial function as estimated from brachial artery flow-mediated, endothelium-dependent vasodilation and nitroglycerine-induced endothelium-independent vasodilation, and plasma levels of the endothelium-derived regulatory proteins, von Willebrand factor (vWF) and endothelin (ET). RESULTS: Raloxifene 60 mg did not significantly affect endothelial function. As compared with placebo, at 6 months of therapy, raloxifene 150 mg and CEE were associated with a mean increase in vWF of 25.5% point (95% CI 3.6-47.3) and 26.6% point (95% CI 6.9-46.3), respectively. At 24 months of therapy, raloxifene 150 mg was associated with a mean decrease in ET of 0.96 pg mL-1 (95% CI -1.57 to -0.36). Raloxifene nor CEE significantly affected endothelium-dependent and/or -independent vasodilation. CONCLUSIONS: Our results suggest that long-term therapy with raloxifene or oral CEE does not affect endothelium-dependent vasodilation in healthy postmenopausal women. Raloxifene 150 mg day-1 might have both positive and negative effects on endothelium. The clinical significance of these findings remains to be investigated.     

A comparison of different balance tests in the prediction of falls in older women with vertebral fractures: a cohort study

BACKGROUND: people with vertebral fractures are at high risk of developing hip fractures. Falls risk is important in the pathogenesis of hip fractures. AIM: to investigate if balance tests, in conjunction with a falls history, can predict falls in older women with vertebral fractures. METHODS: a cohort study of community-dwelling women aged over 60 years, with vertebral fractures. Balance tests investigated were: 5 m-timed-up-and-go-test (5 m-TUG), timed 10 m walk, TURN180 test (number of steps to turn 180 degrees ), tandem walk, ability to stand from chair with arms folded. Leg extensor power was also measured. OUTCOME MEASURE: fallers (at least one fall in a 12 month follow-up period) versus non-fallers. RESULTS: one hundred and four women aged 63-91 years [mean=78 +/- 7], were recruited. Eighty-six (83%) completed the study. Four variables were significantly associated with fallers: previous recurrent faller (2+ falls) [OR=6.52; 95% CI=1.69-25.22], 5 m-TUG test [OR=1.03; 1.00-1.06], timed 10 m walk [OR=1.07; 1.01-1.13] and the TURN180 test [OR=1.22; 1.00-1.49] [P <0.05]. Multi-variable analysis showed that only two variables, previous recurrent faller [OR=5.60; 1.40-22.45] and the 5 m-TUG test [OR=1.04; 1.00-1.08], were independently significantly associated with fallers. The optimal cut-off time for performing the 5 m-TUG test in predicting fallers was 30 s (area under ROC=60%). Combining previous recurrent faller with the 5 m-TUG improved prediction of fallers [OR=16.79, specificity=100%, sensitivity=13%]. CONCLUSIONS: a previous history of recurrent falls and the inability to perform the 5 m-TUG test within 30 s predicted falls in older women with vertebral fractures. Combining these two measures can predict fallers with a high degree of specificity (although a low sensitivity), allowing the identification of a group of patients suitable for fall and fracture prevention measures.     

Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss

Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol, are important factors in the pathogenesis of age-related bone loss. The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women. Four hundred eighty-nine elderly women with normal bone density for their age, aged 65-77 yr, were entered into a randomized double blind, placebo-controlled trial. Women were randomized to one of four groups: conjugated estrogens (0.625 mg, daily) to women without a uterus (estrogen replacement therapy) plus medroxyprogesterone acetate (2.5 mg, daily) to women with a uterus (hormone replacement therapy), calcitriol (0.25 microg twice daily), a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol, or placebos for 3 yr. The primary outcome was the change in bone mineral density of the femoral neck and spine. In the intent to treat analysis, hormone therapy (hormone replacement therapy/estrogen replacement therapy) produced a mean (+/-1 SD) increase in bone mineral density of 2.98% (+/-5.45%) at the femoral neck (P < 0.0001) and 4.36% (+/-6.42%) at the spine (P < 0.0001). There were parallel increases in total hip and trochanter bone mineral density. Calcitriol increased bone mineral density 0.10% (+/- 4.27%) at the femoral neck (P = 0.57) and 1.65% (+/- 4.83%) at the spine (P < 0.0124). The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol increased bone mineral density 3.80% (+/-4.95%) at the femoral neck (P < 0.001), 4.91% (+/-6.0%) at the spine (P < 0.0001), and parallel changes at the total hip and trochanter. All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck, spine, total hip and trochanter. There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis. In a secondary analysis of the effect in women who were adherent to treatment, calcitriol had a more significant effect on spine (P = 0.003) and total hip (P = 0.004). The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups. Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter (P = 0.007) and total hip bone mineral density (P = 0.0017). In summary, hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinically relevant sites in a group of elderly women, with normal bone density for their age. Calcitriol was effective in increasing spine bone mineral density. In the adherent women, combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone.     

Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality

OBJECTIVES: We hypothesized that impaired renal function would also be associated with poorer clinical outcomes among patients with ST-segment elevation myocardial infarction (STEMI) treated with fibrinolysis. BACKGROUND: Previous studies have demonstrated that impaired renal function is associated with poorer clinical outcomes in the setting of unstable angina and non-STEMI and after percutaneous coronary intervention. METHODS: Data were drawn from the Thrombolysis In Myocardial Infarction (TIMI)-10, TIMI-14, and Intravenous nPA for the Treatment of Infarcting Myocardium Early (InTIME-II) trials. RESULTS: Within each TIMI risk score (TRS) for STEMI category (0 to 2, 3 to 4, >/=5), 30-day mortality increased stepwise among patients with normal (creatinine [Cr] 1.2 to 2 mg/dl), and severely (Cr >2.0 mg/dl) impaired renal function (p < 0.001) and in patients with normal (creatinine clearance [CrCl] >/=90 ml/min), mildly (60 to <90 ml/min), moderately (30 to <60 ml/min), and severely (<30 ml/min) impaired CrCl (p < 0.001). Impaired renal function was associated with increased mortality after adjusting for previously identified correlates of mortality (using Cr: odds ratio [OR] for mild impairment 1.52, 95% confidence interval [CI] 1.30 to 1.77, p < 0.001; OR for severe impairment 3.73, 95% CI 2.55 to 5.45, p < 0.001; using CrCl: OR for mild impairment 1.38, 95% CI 1.10 to 1.73, p = 0.006; OR for moderate impairment 2.06, 95% CI 1.59 to 2.66, p < 0.001; OR for severe impairment 3.81, 95% CI 2.57 to 5.65, p < 0.001). CONCLUSIONS: In the setting of STEMI, elevated Cr and/or impaired CrCl on presentation is associated with increased mortality, independent of other conventional risk factors and TRS. This association does not appear to be mediated by reduced fibrinolytic efficacy among patients with impaired renal function or by the presence of congestive heart failure on presentation.     

Calcitriol treatment is not effective in postmenopausal osteoporosis

STUDY OBJECTIVE: To determine if calcitriol is an effective treatment in postmenopausal osteoporosis. DESIGN: Double-blind, randomized clinical trial of 2 years' duration. SETTING: University medical center with patients recruited by media announcements. PATIENTS: Eighty-six postmenopausal women with vertebral compression fractures. INTERVENTIONS: Patients were treated with calcitriol or placebo. Mean dose was 0.43 micrograms/d. Dietary calcium was 1000 mg/d (24.9 mmol/d). The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia. MEASUREMENTS AND MAIN RESULTS: No significant differences between placebo and control groups were seen in the percent change in total body calcium (0.4% +/- 1.0 compared with 0.0% +/- 0.9), single photon absorptiometry (-0.5% +/- 1.2 compared with -3.1% +/- 0.9) or dual photon absorptiometry (0.0% +/- 1.7 compared with -1.0% +/- 2.2). New fractures were seen in 16% of the placebo group and 26% of the calcitriol groups, so the difference in percent fractures was 10% (95% CI, -5.7% to 25.7%). Bone biopsies did not show changes in either group. The calcitriol group had significantly higher serum and urine calcium values, but renal function was not worse than in the placebo group. CONCLUSIONS: Calcitriol is not an effective treatment for established postmenopausal osteoporosis.     

The prognostic value of estimated creatinine clearance alongside functional capacity in ambulatory patients with chronic congestive heart failure

OBJECTIVES: The goal of this study was to determine the prognostic significance of estimated creatinine clearance (CrCl) in relation to 6-min walk distance in ambulatory patients with congestive heart failure (HF). BACKGROUND: Although measurement of renal function is integral to the management of chronic congestive HF, its prognostic implications are not well described and have not been formally evaluated relative to measures of functional capacity. METHODS: We analyzed outcomes of the 585 participants of the 6-min walk substudy of the Digitalis Investigation Group (DIG) trial. The CrCl was estimated using the Cockcroft-Gault equation. Predictors of all-cause mortality were identified using semiparametric Cox proportional hazards regression and completely parametric hazard analyses. RESULTS: Most subjects (85%) were New York Heart Association functional class II and III. Mean age was 65 (+/-12) years and mean ejection fraction (EF) 35% (+/-13%). There were 153 (26%) deaths during a median of 2.6 years of follow-up. Mortality by increasing quartiles of estimated CrCl was 37% (18 to 48 ml/min), 29% (47 to 64 ml/min), 18% (64 to 86 ml/min), and 21% (86 to 194 ml/min) with corresponding hazard ratios (HRs) relative to the top quartile of 2.1 (95% confidence interval [CI], 1.4 to 3.3), 1.6 (95% CI, 1.0 to 2.5), and 0.9 (95% CI, 0.5 to 1.5), respectively. In Cox regression analyses, independent predictors of mortality were estimated CrCl (adjusted HR [quartile 1:quartile 4] 1.5; 95% CI, 1.1 to 2.1), 6-min walk distance < or =262 m [adjusted HR, 1.63; 95% CI, 1.12 to 2.27]), EF, recent hospitalization for worsening HF, and need for diuretic treatment. Parametric (hazard) analysis confirmed consistent effects of estimated CrCl on mortality in several subgroups including that of patients with EF >45%. CONCLUSION: In ambulatory patients with congestive HF, estimated CrCl predicts all-cause mortality independently of established prognostic variables.     

Effectiveness of a multifaceted intervention on falls in nursing home residents

OBJECTIVES: To evaluate the effectiveness of a multifaceted, nonpharmaceutical intervention on incidence of falls and fallers. DESIGN: Prospective, cluster-randomized, controlled 12-month trial. SETTING: Six community nursing homes in Germany. PARTICIPANTS: Long-stay residents (n = 981) aged 60 and older; mean age 85; 79% female. INTERVENTIONS: Staff and resident education on fall prevention, advice on environmental adaptations, progressive balance and resistance training, and hip protectors. MEASUREMENTS: Falls, fallers, and fractures. RESULTS: The incidence density rate of falls per 1,000 resident years (RY) was 2,558 for the control group (CG) and 1,399 for the intervention group (IG) (relative risk (RR) = 0.55, 95% confidence interval (CI) = 0.41-0.73). Two hundred forty-seven (52.3%) fallers were detected in the CG and 188 (36.9%) in the IG (RR = 0.75, 95% CI = 0.57-0.98). The incidence density rate of frequent fallers (>2/year) was 115 (24.4%) for the CG and 66 (13.0%) for the IG (RR = 0.56, 95% CI = 0.35-0.89). The incidence density rate of hip fractures per 1,000 RY was 39 for the CG and 43 for the IG (RR = 1.11, 95% CI = 0.49-2.51). Other fractures were diagnosed with an incidence density rate of 52 per 1,000 RY for CG and 41 per 1,000 RY for IG (RR = 0.78, 95% CI = 0.57-1.07). CONCLUSION: The incidence density rate of falls and fallers differed considerably between the control and intervention groups. The study was underpowered to demonstrate a significant difference of hip or nonhip fractures. Because of a low fracture rate in both groups, the investigation of fracture rates would have required a larger sample size to detect an effect of the intervention.     

A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study

OBJECTIVES: To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents. DESIGN: Secondary data analysis of a previously conducted randomized clinical trial. SETTING: Seven hundred twenty-five-bed long-term care facility. PARTICIPANTS: One hundred twenty-four nursing home residents (average age 89). INTERVENTION: Participants were randomly assigned to receive one of four vitamin D supplement doses (200 IU, 400 IU, 600 IU, or 800 IU) or placebo daily for 5 months. MEASUREMENTS: Number of fallers and number of falls assessed using facility incident tracking database. RESULTS: Over the 5-month study period, the proportion of participants with falls was 44% in the placebo group (11/25), 58% (15/26) in the 200 IU group, 60% (15/25) in the 400 IU group, 60% (15/25) in the 600 IU group, and 20% (5/23) in the 800 IU group. Participants in the 800 IU group had a 72% lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months (rate ratio=0.28; 95% confidence interval=0.11-0.75). No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups. CONCLUSION: Nursing home residents in the highest vitamin D group (800 IU) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses. Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group.     

Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events.

AIMS: To determine whether low-molecular-weight heparin (LMWH)+glycoprotein (GP) IIb/IIIa inhibitors provide greater benefit than unfractionated heparin (UFH)+GP IIb/IIIa inhibitors, irrespective of renal status. METHODS AND RESULTS: Patients in the Global Registry of Acute Coronary Events (GRACE) were divided into three groups according to creatinine clearance (CrCl): normal renal function (CrCl >60 mL/min), moderate renal dysfunction (30相似文献   

Falls risk and functional decline in older fallers discharged directly from emergency departments

BACKGROUND: There is currently no standard approach to falls risk assessment and management for older fallers presenting to the emergency department (ED) who are discharged directly home. Hence, this study was conducted to describe the prevalence of falls risk factors associated with older fallers presenting to the ED and to identify the factors associated with postdischarge decline in function in this group. METHODS: This cross-sectional study was performed with 300 community-dwelling individuals, aged 60 years or older, admitted to the ED following a fall, and discharged directly home. A home-based assessment after ED discharge was performed, which included the prevalence of falls risk factors, identification of functional decline, and objective measurements of balance, gait, depression, and falls efficacy. RESULTS: Fall-related injuries were sustained by 91% (95% confidence interval [CI], 87.2%-94.0%) of participants presenting to the ED. The most common falls risk factors identified in the home assessment were polypharmacy (79.0%, 95% CI, 73.9%-83.5%), home hazards (76.0%, 95% CI, 70.8%-80.7%), decreased balance (61.3%, 95% CI, 55.6%-66.9%), and arthritis (61.3%, 95% CI, 55.6%-66.9%). A decline in function was reported by 35% of participants (95% CI, 29.6%-40.7%). Sustaining a fracture, functional independence before the fall, being female, depression, and slower Timed Up and Go (TUG) scores were associated with a decline in function (p <.05). CONCLUSION: Older fallers discharged directly from the ED have a high prevalence of falls risk factors and are at risk of functional decline.     

Reduced glomerular filtration rate in asymptomatic diabetic patients: predictor of increased risk for cardiac events independent of albuminuria

OBJECTIVES: This study aimed to investigate the prevalence of a reduced glomerular filtration rate (GFR) with and without albuminuria and its ability to predict cardiac events in asymptomatic diabetic patients undergoing stress-rest thallium-201 myocardial perfusion single-photon emission computed tomography. BACKGROUND: Diabetic patients have a higher prevalence of asymptomatic coronary heart disease. Therefore, identifying predictors of cardiac events in asymptomatic diabetic patients is needed. METHODS: In 269 asymptomatic patients, baseline evaluation included diabetes-related complications, including creatinine clearance (CrCl) and albuminuria. During follow-up (mean 2.3 +/- 1.0 years), all cardiac events were recorded. RESULTS: Seventy-seven patients (29%) had a reduced GFR defined by CrCl <60 ml/min/1.73 m(2). Compared with the 177 patients with CrCl >/=60 ml/min/1.73 m(2), the reduced GFR group was older (p < 0.0001), had a longer duration of diabetes (p = 0.002), and had a higher prevalence of albuminuria (p = 0.04). Nevertheless, 35% of the reduced GFR group had normoalbuminuria. Patients with reduced GFR had a significant two-fold increase in total cardiac events (unstable angina, nonfatal myocardial infarction, and cardiac procedures) (25% vs. 13%, p = 0.019), and multivariate analysis found that reduced GFR was an independent predictor of cardiac events (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1 to 4.46). Other independent predictors of cardiac events included stress-induced abnormal myocardial perfusion imaging (OR 3.1, 95% CI 1.3 to 7.5), an electrocardiographic ischemic response (OR 2.7, 95% CI 1.01 to 7.14), and peripheral artery disease (OR 2.1, 95% CI 1.05 to 4.23); however, albuminuria was not. CONCLUSIONS: A reduced GFR was common in our group of asymptomatic diabetic patients and was associated with a two-fold increase in cardiac events. Multivariate analysis found that reduced GFR independent of albuminuria was a significant predictor of cardiac events.     

Effect of genistein on endothelial function in postmenopausal women: a randomized,double-blind,controlled study

PURPOSE: Genistein, a phytoestrogen found in soybeans, corrects endothelial dysfunction induced by oophorectomy in animals. Using a double-blind, controlled, randomized design, we evaluated its effects on endothelial function in women. METHODS: We enrolled 79 healthy postmenopausal women (mean [+/- SD] age, 56 +/- 4 years) and randomly assigned them to receive continuous estrogen/progestin therapy (n = 26; 17beta-estradiol [1 mg/d] combined with norethisterone acetate [0.5 mg/d]), genistein (n = 27; 54 mg/d), or placebo (n = 26). Brachial artery flow-mediated, endothelium-dependent vasodilation and plasma levels of nitrites/nitrates (a marker of nitric oxide metabolism) and endothelin-1 were measured at baseline and after 1 year of therapy. RESULTS: Treatment with genistein increased levels of nitrites/nitrates (mean increase, 21 micromol/L; 95% confidence interval [CI]: 15 to 26 micromol/L; P <0.001 vs. placebo); estrogen/progestin therapy caused similar changes (P <0.001 vs. placebo). Plasma endothelin-1 levels decreased following 12 months of genistein (mean decrease, 7 pg/mL; 95% CI: 3 to 10 pg/mL; P <0.001 vs. placebo) and after 12 months of estrogen/progestin (P <0.001 vs. placebo). When compared with placebo, brachial artery flow-mediated dilation was improved by genistein (mean increase, 5.5%; 95% CI: 3.9% to 7.0%; P <0.001) and by estrogen/progestin (P <0.001). There were no significant differences between estrogen and genistein for any of these parameters (all P >0.4). CONCLUSION: One year of genistein therapy improves endothelium function in postmenopausal women to a similar extent as does an estrogen/progestin regimen.     

Venous thrombosis and conjugated equine estrogen in women without a uterus

BACKGROUND: Postmenopausal hormone therapy has been associated with a 2- to 3-fold increased risk of venous thromboembolism (VT) (including deep vein thrombosis and pulmonary embolism) in observational studies and secondary prevention clinical trials. Clinical trial data on the effects of estrogen alone on VT are limited. METHODS: The Women's Health Initiative estrogen trial enrolled 10 739 women aged 50 to 79 years without a uterus. Participants were randomly assigned to receive conjugated equine estrogen (0.625 mg/d) or placebo. RESULTS: During a mean of 7.1 years, VT occurred in 111 women randomly assigned to receive estrogen (3.0 per 1000 person-years) and 86 randomly assigned to receive placebo (2.2 per 1000 person-years; hazard ratio, 1.32; 95% confidence interval, 0.99-1.75). Deep venous thrombosis was reported in 85 women randomly assigned to receive estrogen (2.3 per 1000 person-years) and 59 randomly assigned to receive placebo (1.5 per 1000 person-years; hazard ratio, 1.47; 95% confidence interval, 1.06-2.06). The VT risk was highest in the first 2 years. There were no significant interactions between estrogen use and age, body mass index, or most other VT risk factors. Comparison of Women's Health Initiative VT findings for estrogen and previous Women's Health Initiative findings for estrogen plus progestin showed that the hazard ratios for estrogen plus progestin were significantly higher than those for estrogen alone (P = .03), even after adjusting for VT risk factors. CONCLUSION: An early increased VT risk is associated with use of estrogen, especially within the first 2 years, but this risk increase is less than that for estrogen plus progestin.     

Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily

OBJECTIVES: To study the effect of alfacalcidol (1alpha(OH)D3) on fall risk in community-dwelling elderly men and women. DESIGN: Randomized, double-blind, placebo-controlled intervention trial. SETTING: Basel, Switzerland. PARTICIPANTS: Three hundred seventy-eight community-dwelling elderly (191 women/187 men). INTERVENTION: Participants were randomly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks. MEASUREMENTS: Serum 25-hydoxyvitamin D3 (25(OH) D,1,25-dihydroxyvitamin D3 (D-hormone), and intact parathormone (iPTH) levels were measured using radioimmunoassay at baseline and every 12 weeks. Numbers of fallers and falls were assessed using a questionnaire during each study site visit. Dietary calcium intake was assessed at baseline using a food frequency questionnaire. RESULTS: At baseline, participants had, on average, normal vitamin D and D-hormone serum levels. Over 36 weeks, alfacalcidol treatment was associated with fewer fallers (odds ratio (OR)=0.69, 95% confidence interval (CI)=0.41-1.16) than placebo. In a post hoc subgroups analysis by medians of total calcium intake, this reduction reached significance in alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d (OR=0.45, 95% CI=0.21-0.97, P=.042) but not in those who consumed less than 512 mg/d (OR=1.00, 95% CI= 0.47-2.11, P=.998). Alfacalcidol treatment was also, independent of total calcium intake, associated with a significant 37.9% reduction in iPTH serum levels (P<.0001). No cases of clinically relevant hypercalcemia were observed. CONCLUSION: Provided a minimal calcium intake of more than 512 mg/d, alfacalcidol treatment significantly and safely reduces number of fallers in an elderly community dwelling population.     

Risk factors associated with falls among Chinese hospital inpatients in Taiwan

Falls among hospital inpatients were not uncommon and were associated with physical, functional and psychological morbidity for patients and excess cost, bed occupancy, complaints and litigation for hospitals. Risk factors for falls of hospital inpatients have been reported, but rarely in a case-control design. To our best knowledge, there was no case-control study for risk of fall among hospital inpatients in Taiwan, one of the most rapidly aging countries. The main purpose of this study was to determine risk factors for falls among hospital inpatients in Taiwan. A prospective multi-center case-control study was started in 2002. During the study period, all incident falls reported by ward nurses were carefully reviewed by research staff on the next day, and a matched control subject was generated according to the age, sex, diagnosis, and pre-event length of stay. Risk factors of falls, including physical conditions, pharmaceutical agents, and environmental factors were compared between fallers and controls. In total, 202 incident falls (202 fallers, none of them fell twice, mean age: 68.2+/-16.9 years, 73.8% males) were reported and the overall incidence of falls during the study period was 4.4 per 1000 bed days. Leg weakness (odds ratio (OR): 1.88, 95% confidence interval (CI): 1.16-3.05), reported insomnia at admission (OR: 2.28; 95% CI: 1.06-4.89), postural hypotension (OR: 5.57; 95% CI: 1.54-21.46), previous history of fall within 1 year before admissions (OR: 5.05, CI: 2.60-9.78), recent use of hypnotics (within 24h) (OR: 1.86, 95% CI: 1.10-3.14) were all significant risk factors (for all comparisons p<0.05), but family member's company may reduce in-hospital falls (OR: 0.51; 95% CI: 0.33-0.78). In conclusion, the incidence of falls among hospital inpatients was lower than that reported from other countries. Further study is needed to organize a comprehensive fall prevention program according to the risk factors identified in this study to reduce in-hospital falls in Taiwan.     

Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative

OBJECTIVE: To determine the effect of hormone therapy on arthroplasty rates. METHODS: We examined data from the Women's Health Initiative placebo-controlled, double-blind, randomized trials. Community-dwelling women ages 50-79 years were enrolled at 40 US clinics. Women with prior arthroplasty were excluded, yielding a sample size of 26,321 subjects. Women who had had hysterectomies (n = 10,272) were randomly assigned to receive 0.625 mg/day conjugated equine estrogens (n = 5,076), or placebo (n = 5,196), with a mean followup of 7.1 years. Those who had not had hysterectomies (n = 16,049) were randomly assigned to receive estrogen plus progestin (n = 8,240), given as 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate, or placebo (n = 7,809), with a mean followup of 5.6 years. Participants reported hospitalizations, and arthroplasties were identified by procedure codes. Arthroplasties due to hip fracture were censored. Cox proportional hazards regression was used to assess hazard ratios (HRs) and 95% confidence intervals (95% CIs) using intent-to-treat methods and outcome of time to first procedure. RESULTS: In the estrogen-alone trial, women receiving hormone therapy had significantly lower rates of any arthroplasty (HR 0.84 [95% CI 0.70-1.00], P = 0.05). However, this effect was borderline statistically significant for hip arthroplasty (HR 0.73 [95% CI 0.52-1.03], P = 0.07), and not significant for knee arthroplasty (HR 0.87 [95% CI 0.71-1.07], P = 0.19). In the estrogen-plus-progestin trial, there was no association for total arthroplasty (HR 0.99 [95% CI 0.82-1.20], P = 0.92) or for individual hip (HR 1.14 [95% CI 0.83-1.57], P = 0.41) or knee (HR 0.91 [95% CI 0.72-1.15], P = 0.41) arthroplasties. CONCLUSION: These data suggest that hormone therapy may influence joint health, but this observed decrease in risk may be limited to unopposed estrogen and may possibly be more important in hip than in knee osteoarthritis.     

Treatment effects of eptifibatide in planned coronary stent implantation in patients with chronic kidney disease (ESPRIT Trial)

The role of platelet glycoprotein IIb/IIIa inhibitor therapy in patients with mild renal impairment is not well characterized. Our objective was to explore the associations of creatinine clearance (CrCl) with outcomes in a trial of eptifibatide therapy in patients who underwent percutaneous coronary intervention (PCI). We analyzed 48-hour and 30-day outcomes of patients enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial. Patients were randomly assigned to placebo or eptifibatide as an adjunct to stent implantation (1,755 with CrCl > or =60 ml/min and 289 with CrCl <60 ml/min). CrCl was calculated using the Cockcroft and Gault formula, and the associations of CrCl with outcomes were evaluated using logistic regression models. Patients with CrCl <60 ml/min were more likely to be older, women, hypertensive, and have a history of coronary artery bypass surgery, stroke, or peripheral vascular disease. The interaction of eptifibatide with CrCl had borderline significance for the 30-day outcome (p = 0.109). Treatment effect trended toward a greater magnitude in patients with lower CrCl (60 ml/min) (odds ratio 0.53, confidence interval 0.34 to 0.83) compared with those with higher CrCl (90 ml/min) (odds ratio 0.68, confidence interval 0.49 to 0.94). An accompanying increase in bleeding risk also was not apparent with lower CrCl. The treatment effect of eptifibatide is realized regardless of renal function and trends toward being greater in patients with mild renal impairment.     

Alveolar and postcranial bone density in postmenopausal women receiving hormone/estrogen replacement therapy: a randomized,double-blind,placebo-controlled trial

BACKGROUND: We conducted a 3-year, double-blind, randomized, placebo-controlled study to determine whether the positive effects of hormone/estrogen replacement therapy (H/ERT) on postcranial bone density are accompanied by similar positive effects on oral bone mass. METHODS: A total of 135 postmenopausal women (aged 41-70 years) with no evidence of moderate or severe periodontal disease were randomized to receive daily oral conjugated estrogen (Premarin; 0.625 mg) alone or in combination with medroxyprogesterone acetate (Prempro; 0.625 and 2.5 mg, respectively) or placebo. All subjects received calcium carbonate (1000 mg/d) and cholecalciferol (400 [corrected] IU/d) supplements. The primary efficacy end points were the changes in alveolar crest height and alveolar bone density. Alveolar crest height was measured on bite-wing radiographs, and changes in alveolar bone mass were assessed by means of digital-subtraction radiography. Postcranial bone density was measured in the lumbar spine and left proximal femur by means of dual-energy x-ray absorptiometry. RESULTS: Hormone/estrogen replacement therapy significantly increased alveolar bone mass compared with placebo (+1.84% vs +0.95% [P =.04]), and tended to improve alveolar crest height (+4.83% vs +3.46% [P =.34]). Bone mineral density of the proximal femur significantly increased in the H/ERT compared with the placebo group (total proximal femur, +3.59% vs +0.22% [P =.001]; neck, +2.05% vs -0.34% [P =.02]; trochanter, +3.49% vs +0.08% [P<.001]), but not the lumbar spine (+1.01% vs +0.17% [P =.39]). Changes in alveolar bone mass correlated with bone density changes in the total femur (r = 0.28 [P =.02]) and femoral trochanter (r = 0.25 [P =.04]) in the H/ERT but not in the placebo group. CONCLUSIONS: Postcranial and oral bone mass were increased in postmenopausal women receiving H/ERT. Improvement in oral bone health constitutes an additional benefit of H/ERT.     

Consequences of falling in older men and women and risk factors for health service use and functional decline

OBJECTIVES: (1) to examine consequences of falls in older men and women and (2) to examine risk factors for health service use and functional decline among older fallers. METHODS: the study was performed within the Longitudinal Aging Study Amsterdam. In 1998/1999, potential risk factors were assessed during the third data collection. In 1999/2000, 204 community-dwelling persons (> or =65 years) who reported at least one fall in the year before the interview, were asked about consequences of their last fall, including physical injury, health service use, treatment and functional decline (i.e. decline in functional status, social and physical activities). RESULTS: as a consequence of falling, respondents reported physical injury (68.1%), major injury (5.9%), health service use (23.5%), treatment (17.2%), and decline in functional status (35.3%), and social (16.7%) and physical activities (15.2%). Using multivariate logistic regression, specific risk factors for health service use after falling could not be identified. Female gender (OR = 2.8, 95% CI = 1.5-5.1), higher medication use (OR = 1.5, 95% CI = 1.0-2.2) and depressive symptoms (OR = 1.9, 95% CI = 1.3-2.8) were independently associated with functional decline after falling. Depressive symptoms (OR = 2.0, 95% CI = 1.2-3.3) and falls inside (OR = 2.6, 95% CI = 1.1-6.5) were risk factors for decline in social activities, while female gender (OR = 2.7, 95% CI = 1.1-7.0) and depressive symptoms (OR = 1.9, 95% CI = 1.2-3.0) were risk factors for decline in physical activities after falling. CONCLUSIONS: almost 70% of the respondents suffered physical injury, almost one-quarter used health services and more than one-third suffered functional decline after falling. No risk factors were found for health service use needed after falling. Female gender, higher medication use, depressive symptoms and falls inside were risk factors for functional decline after falling.