Longitudinal changes in calcium and vitamin D intakes and relationship to bone mineral density in a prospective population-based study: the Canadian Multicentre Osteoporosis Study (CaMos).

OBJECTIVES: Our objective was to study changes in calcium and vitamin D intakes over time, and their cross-sectional and longitudinal associations with bone mineral density (BMD). METHODS: We followed 9382 women and men aged ≥25 and 899 aged 16-24, for 10 and 2 years respectively. RESULTS: Calcium and vitamin D intakes increased over time in adults, but decreased in women aged 16-18. The increased intakes in adults were largely attributable to the increased use of calcium and/or vitamin D supplements. Both the percentage of supplement users and average dose among users increased over time. There was nevertheless a high prevalence of calcium and vitamin D intake below the estimated average requirement. At baseline, higher calcium and vitamin D intakes were associated with higher total hip and femoral neck BMD in young men, and cumulatively high levels of calcium and vitamin D intakes over time contributed to better BMD maintenance at lumbar spine and hip sites in adult women. CONCLUSIONS: Although total intakes, particularly of vitamin D, frequently fell below the Institute of Medicine recommendations despite an increase over time in supplement use, we found some positive associations between total calcium and vitamin D intake and bone health.

Delay of adequate empiric antibiotic therapy is associated with increased mortality among solid-organ transplant patients.

Empiric antibiotic therapy is often prescribed prior to the availability of bacterial culture results. In some cases, the organism isolated may not be susceptible to initial empiric therapy (inadequate empiric therapy or IET). In solid-organ transplant recipients, the overall incidence and clinical importance of IET is unknown. We performed a retrospective cohort study of patients admitted from 2002 to 2004. Multiple logistic regression analyses were conducted to determine associations between potential determinants and mortality. IET was administered in 169/312 (54%) patients, with a hospital mortality rate that was significantly greater than those receiving adequate therapy (24.9% vs. 7.0%; relative risk [RR] 3.55; 95% confidence interval [CI], 1.85-6.83; p < 0.001). Regression analysis demonstrated that an increasing duration of IET (adjusted odds ratio [OR] at 24 h: 1.33; 95% CI: 1.15-1.53; p < 0.001), ICU-associated infections (adjusted OR: 6.27; 95% CI: 2.79-14.09; p < 0.001), prior antibiotic use (adjusted OR: 3.56; 95% CI: 1.51-8.41; p = 0.004) and increasing APACHE-II scores (adjusted OR: 1.26; 95% CI: 1.16-1.34; p < 0.001) were independently correlated with hospital mortality. IET is common and appears to be associated with an increased hospital mortality rate in the solid-organ transplant population.

Hip protectors decrease hip fracture risk in elderly nursing home residents: a Bayesian meta-analysis.

OBJECTIVE: To design a Bayesian random effects model for pooling binary outcome data from cluster randomized trials (CRTs) with individually randomized trials (IRTs) and then use this model to determine if hip protectors decrease the risk of hip fracture in elderly nursing home residents. STUDY DESIGN AND SETTING: Eight electronic databases were searched; abstracts and papers were reviewed in duplicate. Randomized controlled trials of hip protectors in nursing homes were included. The pooled mean odds ratio (OR) of a hip fracture in an individual allocated to hip protectors with 95% credibility interval (CRI) was calculated. RESULTS: We included four trials of 1,922 individuals (including three CRTs). The pooled OR of an elderly nursing home resident sustaining one or more hip fractures with hip protector allocation was 0.40 (95% CRI 0.25, 0.61). The model was robust in multiple sensitivity analyses assuming alternative intracluster correlation coefficient values. CONCLUSION: The Bayesian approach may be used in meta-analyses of IRTs and CRTs. Using this approach, we have determined that hip protectors decrease the risk of hip fracture in elderly nursing home residents. Methodologic limitations of the included trials and a possible herd effect in CRTs may have influenced these results.

Could a policy of provision of hip protectors to elderly nursing home residents result in cost savings in acute hip fracture care? The case of Ontario, Canada.

UNLABELLED: Hip fractures are an important problem in nursing homes. Hip protectors are external devices that decrease the risk of hip fracture in elderly nursing home residents. We estimated the overall healthcare cost savings from a hypothetical strategy of provision of hip protectors to elderly nursing home residents in Ontario, Canada. In a recent meta-analysis, we determined that a strategy of provision of hip protectors decreases the risk of hip fracture in nursing home residents. INTRODUCTION: Our objective was to determine whether the provision of hip protectors to all Ontario nursing home residents aged > or =65 years could result in cost savings, stemming from reductions in initial hospitalizations for hip fracture. METHODS: We conducted a cost analysis from a Ministry of Health perspective (one year cycle length). The efficacy of the intervention was estimated from a meta-analysis of randomized controlled trials. RESULTS: A strategy of provision of hip protectors to all 60,775 elderly Ontario nursing home residents could result in an overall mean cost savings of 6.0 million Canadian dollars in one year (95% credibility interval, -26.4 million, 39.7 million), with a probability of cost savings of 0.63 (assuming no additional labor costs). In sensitivity analyses, decreasing hip protector price increased cost savings, whereas additional labor expenditures for application for hip protectors decreased cost savings. CONCLUSION: In conclusion, if hip protectors can be provided to elderly Ontario nursing home residents without additional labor expenditures, there is a reasonable probability that such a strategy may result in healthcare cost savings.

What is the number of older Canadians needed to screen by measurement of bone density to detect an undiagnosed case of osteoporosis? a population-based study from CaMos.

Routine bone mineral densitometry (BMD) screening has been recommended for women aged >or=65 yr (Osteoporosis Canada [OC], International Society for Clinical Densitometry [ISCD], Canadian and United States Task Forces on Preventative Healthcare, and National Osteoporosis Foundation) and for men >or=65 yr (OC) or >or=70 yr (ISCD). We estimated the number of older Canadians needed to screen (NNS) by BMD to detect an undiagnosed case of osteoporosis, using prospective, multicenter, population-based data from the Canadian Multicentre Osteoporosis Study (CaMos). We included participants aged >or=65 yr with baseline dual-energy X-ray absorptiometry (DXA) BMDs at the femoral neck and lumbar spine (L1-L4). Osteoporosis was defined by a T-score or=65 yr. The percentage prevalence and 95% confidence intervals were determined. In individuals aged >or=65 yr, the prevalence of osteoporosis was 25.6% in women (95% confidence interval, 24.0%, 27.3%) and 8.9% in men (7.3%, 10.8%). In 652 men aged >or=70 yr, the prevalence of osteoporosis was 11.3% (9.1%, 14.0%). Of the participants with BMD-defined osteoporosis, 76.6% of woman aged >or=65 yr (73.2%, 79.6%; 516 of 674 women), 93.4% of men aged >or=65 yr (86.4%, 96.9%; 85 of 91), and 93.2% of men >or=70 yr (84.9%, 97.0%; 68 of 73) were not aware of it. Thus, the minimum NNS by BMD testing to detect one previously undiagnosed case of osteoporosis in Canada is: 6 women aged >or=65 yr, 13 men aged >or=65 yr, and 10 men aged >or=70 yr.

Health-related quality of life measurements in elderly Canadians with osteoporosis compared to other chronic medical conditions: a population-based study from the Canadian Multicentre Osteoporosis Study (CaMos).

The objective of this research was to determine the relative decrement in health-related quality of life, as measured by the health utilities index mark 3 (HUI3), in osteoporosis compared to other chronic medical conditions. The impact of chronic medical conditions other than osteoporosis on HUI3 measurements had been previously established in the 1996/1997 Canadian National Population Health Survey (NPHS). The Canadian Multicentre Osteoporosis Study (CaMos) is a national population-based study in which regional participants were randomly recruited, regardless of presence of osteoporosis. We analyzed data from participants aged > or = 65 years who completed a baseline HUI3 questionnaire and provided information on their medical history (n=3,750). We determined the age- and gender-adjusted mean decrement in HUI3 for several chronic medical conditions, including osteoporosis. The mean changes in HUI3 adjusted for age and gender (with 95% confidence intervals) were as follows: arthritis -0.10 (-0.11, -0.09), chronic obstructive pulmonary disease (COPD) -0.07 (-0.09, -0.05), diabetes mellitus -0.05 (-0.08, -0.03), heart disease -0.06 (-0.08, -0.04), hypertension -0.02 (-0.03, -0.01), and osteoporosis -0.08 (-0.11, -0.06), respectively (model r2=0.17; P<0.0001). These findings were comparable to those observed in the NPHS, with the exception of osteoporosis, which had not been previously studied in this fashion. The decrement in HUI3 score seen in participants with osteoporosis was comparable to that observed in other chronic medical conditions, such as arthritis, COPD, diabetes mellitus or heart disease.

The association between osteoporotic fractures and health-related quality of life as measured by the Health Utilities Index in the Canadian Multicentre Osteoporosis Study (CaMos).

Osteoporotic fractures can be a major cause of morbidity. It is important to determine the impact of fractures on health-related quality of life (HRQL). A total of 3,394 women and 1,122 men 50 years of age and older, who were recruited for the Canadian Multicentre Osteoporosis Study (CaMos), participated in this cross-sectional study. Minimal trauma fractures of the hip, pelvis, spine, lower body (included upper and lower leg, knee, ankle, and foot), upper body (included arm, elbow, sternum, shoulder, and clavicle), wrist and hand (included forearm, hand, and finger), and ribs were studied. Participants with subclinical vertebral deformities were also examined. The Health Utilities Index Mark II and III Systems were used to assess HRQL. Past osteoporotic fractures varied in prevalence from 1.2% (pelvis) to 27.8% (lower body) in women and 0.3% (pelvis) to 29.3% (wrist) in men. Multivariate linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] indicated that minimal trauma fractures were negatively associated with HRQL and that this relationship depends on fracture type and gender. The multi-attribute scores for the Mark II system were negatively related to hip (-0.05; 95% CI: -0.09, -0.01), lower body (-0.02; 95% CI: -0.03, -0.000), and subclinical vertebral fractures (-0.02; 95% CI: -0.03, -0.00) for women. The multi-attribute scores for the Mark III system were negatively related to hip (-0.09; 95% CI: -0.14, -0.03) and rib fractures (-0.06; 95% CI: -0.11, -0.00) for women, and rib fractures (-0.06; 95% CI: -0.12, -0.00) for men. In conclusion, this study demonstrates a negative association between osteoporotic fractures and quality of life in both women and men.

The impact of risk on preference values: implications for evaluations of postmenopausal osteoporosis therapy.

OBJECTIVE: The objective was to assess the impact of different levels of risk of disease on a woman's preferences for health states. Women were provided with health scenarios incorporating different levels of lifetime risks for breast cancer, hip fracture, and coronary heart disease (CHD). In this way, we were able to determine the incremental effect of changes in risks of each disease on preference values. METHODS AND DATA: Preference values and utility scores were obtained for six health scenarios by both the feeling thermometer (FT) and standard gamble (SG) methods. Scenarios presented the different lifetime risks of CHD, breast cancer, and hip fracture associated with and not associated with long-term use of hormone replacement therapy (HRT) and raloxifene. Risks of breast cancer were based on perceived risks and population risks. The sample population consisted of 40 healthy female volunteers aged between 45 and 65 years randomly selected from the Ottawa-Carleton district. RESULTS: Based on their perceived risk of breast cancer, the women had higher value scores for the raloxifene risk profile than for both HRT (p = .002) and no therapy (p = .003), with similar results for analyses based on population risks and from utility scores. Regression analysis showed that the risk of breast cancer (p < .001) was the only disease risk that was statistically significantly associated with women's preferences. CONCLUSIONS: Women had significant preferences over the different risk profiles, primarily due to the incremental effect on changes in values for the risk of breast cancer. Therefore, studies evaluating therapies for osteoporosis should consider patient preferences for living with different risk profiles.

Economic implications of hip fracture: health service use, institutional care and cost in Canada.

As the burden of illness associated with hip fracture extends beyond the initial hospitalization, a longitudinal 1 year cohort study was used to analyze levels of health service use, institutional care and their associated costs, and to examine patient and residency factors contributing to overall 1 year cost. Patients in the study were aged 50 year and over, and had been admitted to an acute care facility for hip fracture in the Hamilton-Wentworth region of Canada from 1 April 1995 to 31 March 1996. Health care resources assessed included initial hospitalization, rehospitalization, rehabilitation, chronic care, home care, long-term care (LTC) and informal care. Regression analysis was used to determine the effects of age, gender, residence, survival and days of follow-up on 1 year cost. The mean 1 year cost of hip fracture for the 504 study patients was 26,527 Canadian dollars (95% Cl: $24,564-$28,490). One year costs were significantly different for patients who returned to the community ($21,385), versus those who were transferred to ($44,156), or readmitted to LTC facilities ($33,729) (p < 0.001). Initial hospitalization represented 58% of 1 year cost for community-dwelling patients, compared with 27% for LTC residents. Only 59.4% of community-dwelling patients resided in the community 1 year following hip fracture, and 5.6% of patients who survived their first fracture experienced a subsequent hip fracture. Linear regression indicated place of residence, age and survival were all important contributors to 1 year cost (p < 0.001). While the average 1 year cost of care was $26,527, the overall cost varied depending on a patient's place of residence, age, and survival to 1 year. Annual economic implications of hip fracture in Canada are $650 million and are expected to rise to $2.4 billion by 2041.

The influence of osteoporotic fractures on health-related quality of life in community-dwelling men and women across Canada.

Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fractures were of three categories: clinically recognized main fractures, subclinical vertebral fractures and fractures at other sites. Main fractures were divided and analyzed at the hip, spine, wrist/forearm, pelvis and rib sites. Baseline assessments of anthropometric data, medical history, therapeutic drug use, spinal radiographs and prevalent fractures were obtained from all participants. The SF-36 instrument was used as a tool to measure HRQL. A total of 652 (13.5%) main fractures were reported. Results indicated that hip, spine, wrist/forearm, pelvis and rib fractures had occurred in 78 (1.6%), 40 (0.8%), 390 (8.1%), 19 (0.4%) and 125 (2.6%) individuals, respectively (subjects may have had more than one main fracture). Subjects who had experienced a main prevalent fracture had lower HRQL scores compared with non-fractured participants. The largest differences were observed in the physical functioning (-4.0; 95% confidence intervals (CI): -6.0, -2.0) and role-physical functioning domains (-5.8; 95% CI: -9.5, -2.2). In women, the physical functioning domain was most influenced by hip (-14.9%; 95% CI: -20.9, -9.0) and pelvis (-18.1; 95% CI: -27.6, -8.6) fractures. In men, the role-physical domain was most affected by hip fractures (-35.7; 95% CI: -60.4, -11.1). Subjects who experienced subclinical vertebral fractures had lower HRQL scores than those without prevalent fractures. In conclusion, HRQL was lower in the physical functioning domain in women and the role-physical domain in men who sustained main fractures at the hip. Subclinical vertebral fractures exerted a moderate effect on HRQL.

Canadian normative data for the SF-36 health survey. Canadian Multicentre Osteoporosis Study Research Group.

BACKGROUND: The Medical Outcomes Study 36-item Short Form (SF-36) is a widely used measure of health-related quality of life. Normative data are the key to determining whether a group or an individual scores above or below the average for their country, age or sex. Published norms for the SF-36 exist for other countries but have not been previously published for Canada. METHODS: The Canadian Multicentre Osteoporosis Study is a prospective cohort study involving 9423 randomly selected Canadian men and women aged 25 years or more living in the community. The sample was drawn within a 50-km radius of 9 Canadian cities, and the information collected included the SF-36 as a measure of health-related quality of life. This provided a unique opportunity to develop age- and sex-adjusted normative data for the Canadian population. RESULTS: Canadian men scored substantially higher than women on all 8 domains and the 2 summary component scales of the SF-36. Canadians scored higher than their US counterparts on all SF-36 domains and both summary component scales and scored higher than their UK counterparts on 4 domains, although many of the differences are not large. INTERPRETATION: The differences in the SF-36 scores between age groups, sexes and countries confirm that these Canadian norms are necessary for comparative purposes. The data will be useful for assessing the health status of the general population and of patient populations, and the effect of interventions on health-related quality of life.

Current and projected rates of hip fracture in Canada.

OBJECTIVE: To determine the current values and estimate the projected values (to the year 2041) for annual number of proximal femoral fractures (PFFs), age-adjusted rates of fracture, rates of death in the acute care setting, associated length of stay (LOS) in hospital, and seasonal variation by sex and age in elderly Canadians. DESIGN: Hospital discharge data for fiscal year 1993-94 from the Canadian Institute for Health Information were used to determine PFF incidence, and Statistics Canada population projections were used to estimate the rate and number of PFFs to 2041. SETTING: Canada. PARTICIPANTS: Canadian patients 65 years of age or older who underwent hip arthroplasty. OUTCOME MEASURES: PFF rates, death rates and LOS by age, sex and province. RESULTS: In 1993-94 the incidence of PFF increased exponentially with increasing age. The age-adjusted rates were 479 per 100,000 for women and 187 per 100,000 for men. The number of PFFs was estimated at 23,375 (17,823 in women and 5552 in men), with a projected increase to 88,124 in 2041. The rate of death during the acute care stay increased exponentially with increasing age. The death rates for men were twice those for women. In 1993-94 an estimated 1570 deaths occurred in the acute care setting, and 7000 deaths were projected for 2041. LOS in the acute care setting increased with advancing age, as did variability in LOS, which suggests a more heterogeneous case mix with advancing age. The LOS for 1993-94 and 2041 was estimated at 465,000 and 1.8 million patient-days respectively. Seasonal variability in the incidence of PFFs by sex was not significant. Significant season-province interactions were seen (p < 0.05); however, the differences in incidence were small (on the order of 2% to 3%) and were not considered to have a large effect on resource use in the acute care setting. CONCLUSIONS: On the assumption that current conditions contributing to hip fractures will remain constant, the number of PFFs will rise exponentially over the next 40 years. The results of this study highlight the serious implications for Canadians if incidence rates are not reduced by some form of intervention.

Deformation kinetics of potassium bromide crystals predict tablet stress relaxation.

A model relating the interparticulate contact stress within a tablet matrix with the compaction stress was developed previously to permit the nonlinear deformation kinetic analysis of the viscoelastic behavior of pharmaceutical tablets with the known properties of the tablet constituents. The present research was undertaken to determine whether the inverse operation (i.e., using tablet stress relaxation to determine single crystal properties) was possible. The stress relaxation of potassium bromide (KBr) compacts was evaluated as a function of temperature and relative density, and an attempt was made to calculate the deformation kinetic parameters. The stress relaxation of KBr did not fit the model under ambient conditions for two reasons: (1) KBr has two slip systems with approximately the same shear stress at room temperature; and (2) KBr strain-hardens. When these complications were taken into consideration, the stress relaxation behavior could be explained. Therefore, whereas single crystal tests are capable of yielding parameters that can be used to predict compact behavior, the inverse process of quantifying fundamental material parameters from compact behavior is problematic due to the difficulty of determining, a priori, all the processes that operate simultaneously.

Predicting the postconsolidation relaxation behavior of sodium chloride tablets.

A model that relates the interparticulate contact stress within a tablet matrix with the compaction stress has been developed. The model permits the application of nonlinear deformation kinetic analysis to quantification of the viscoelastic behavior of tablet constituents. Deformation kinetic analysis assumes that stress relaxation is controlled by thermally activated processes similar in character to those associated with chemical reaction kinetics. The model was tested by measuring the stress relaxation of sodium chloride compacts as a function of temperature and relative density. The experimental activation parameters agree with literature values within experimental errors.