Validation of a one year fracture prediction tool for absolute hip fracture risk in long term care residents.

BACKGROUND: Frail older adults living in long term care (LTC) homes have a high fracture risk, which can result in reduced quality of life, pain and death. The Fracture Risk Scale (FRS) was designed for fracture risk assessment in LTC, to optimize targeting of services in those at highest risk. This study aims to examine the construct validity and discriminative properties of the FRS in three Canadian provinces at 1-year follow up. METHODS: LTC residents were included if they were: 1) Adults admitted to LTC homes in Ontario (ON), British Columbia (BC) and Manitoba (MB) Canada; and 2) Received a Resident Assessment Instrument Minimum Data Set Version 2.0. After admission to LTC, one-year hip fracture risk was evaluated for all the included residents using the FRS (an eight-level risk scale, level 8 represents the highest fracture risk). Multiple logistic regressions were used to determine the differences in incident hip or all clinical fractures across the provinces and FRS risk levels. We examined the differences in incident hip or all clinical fracture for each FRS level across the three provinces (adjusted for age, BMI, gender, fallers and previous fractures). We used the C-statistic to assess the discriminative properties of the FRS for each province. RESULTS: Descriptive statistics on the LTC populations in ON (n = 29,848), BC (n = 3129), and MB (n = 2293) are: mean (SD) age 82 (10), 83 (10), and 84 (9), gender (female %) 66, 64, and 70% respectively. The incident hip fractures and all clinical fractures for FRS risk level were similar among the three provinces and ranged from 0.5 to 19.2% and 1 to 19.2% respectively. The overall discriminative properties of the FRS were similar between ON (C-statistic = 0.673), BC (C-statistic = 0.644) and MB (C-statistic = 0.649) samples. CONCLUSION: FRS is a valid tool for identifying LTC residents at different risk levels for hip or all clinical fractures in three provinces. Having a fracture risk assessment tool that is tailored to the LTC context and embedded within the routine clinical assessment may have significant implications for policy, service delivery and care planning, and may improve care for LTC residents across Canada.

Fracture risk in long term care: a systematic review and meta-analysis of prospective observational studies.

BACKGROUND: The risk factors associated with fractures have been well-characterized in community dwelling populations, but have not been clearly defined in long-term care (LTC) settings. The objective of this review was to identify risk factors for fractures in LTC settings. METHODS: We searched MEDLINE, the Cochrane Library, EMBASE and CINAHL up to June 2014, scanned reference lists of articles and consulted with experts in the field to identify relevant prospective cohort studies that evaluated risk factors associated with fracture incidence in LTC. We included studies that assessed the association between risk factors included in the WHO-Fracture Risk Assessment Tool (FRAX®) or other predictors relevant to LTC (psychotropic medications, cognitive impairment, mobility, and falls). All articles were screened and extracted by two authors. Available data on the association between a given risk factor and fracture incidence were pooled when possible. We used the GRADE criteria to provide a summary of evidence. The GRADE approach defines the quality of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the quantity of specific interest. RESULTS: We identified 13 prospective cohort studies which examined fracture incidence among LTC residents. Most predictors showed moderate increases in fracture risk, but the quality of the evidence was often low. Moderate quality evidence showed that prior fractures and falls may moderately increase the risk of fractures. Being a woman and cognitive impairment are probably associated with a small increase. The effect of mobility and psychotropic medication use is still uncertain primarily due to the various definitions used in the studies and difficulty summarising the results. CONCLUSIONS: In addition to criteria used in the FRAX assessment tool, such as a previous fracture and female gender, we found that falls and cognitive impairment are also associated with a small to moderate increases in the risk of fractures in LTC. Developing an assessment tool that includes risk factors that are specific to LTC may improve the identification of individuals who can benefit from fracture prevention programs in these settings.

Frailty index of deficit accumulation and falls: data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort.

BACKGROUND: To investigate the association between frailty index (FI) of deficit accumulation and risk of falls, fractures, death and overnight hospitalizations in women aged 55 years and older. METHODS: The data were from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort. In this 3-year longitudinal, observational cohort study, women (N=3,985) aged ≥ 55 years were enrolled between May 2008 and March 2009 in Hamilton, Canada. A FI including co-morbidities, activities of daily living, symptoms and signs, and healthcare utilization was constructed using 34 health deficits at baseline. Relationship between the FI and falls, fractures, death and overnight hospitalizations was examined. RESULTS: The FI was significantly associated with age, with a mean rate of deficit accumulation across baseline age of 0.004 or 0.021 (on a log scale) per year. During the third year of follow-up, 1,068 (31.89%) women reported at least one fall. Each increment of 0.01 on the FI was associated with a significantly increased risk of falls during the third year of follow-up (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02-1.03). The area under the curve (AUC) of the predictive model was 0.69 (95% CI: 0.67-0.71). Results of subgroup and sensitivity analyses indicated the relationship between the FI and risk of falls was robust, while bootstrap analysis judged its internal validation. The FI was significantly related to fractures (hazard ratio [HR]: 1.02, 95% CI: 1.01-1.03), death (OR: 1.05, 95% CI: 1.03-1.06) during the 3-year follow-up period and overnight hospitalizations (incidence rate ratio [IRR]: 1.02, 95% CI: 1.02-1.03) for an increase of 0.01 on the FI during the third year of follow-up. Measured by per standard deviation (SD) increment of the FI, the ORs were 1.21 and 1.40 for falls and death respectively, while the HR was 1.17 for fractures and the IRR was 1.18 for overnight hospitalizations respectively. CONCLUSION: The FI of deficit accumulation increased with chronological age significantly. The FI was associated with and predicted increased risk of falls, fractures, death and overnight hospitalizations significantly.

The burden of osteoporotic fractures beyond acute care: the Canadian Multicentre Osteoporosis Study (CaMos).

BACKGROUND: the burden associated with osteoporotic fractures has commonly been reported in terms of utilisation of acute care. However, individuals with fractures suffer lasting deficits in quality of life and the burden of care extends well beyond the initial acute care period. The burden of fractures related to post-acute heath care utilisation, and informal care giving, has not been sufficiently addressed. We examine the use of formal and informal post-acute care in men and women 50 years and older who sustained fractures. METHODS: the study sample consisted of 1,116 men and women from the Canadian Multicentre Osteoporosis Study (CaMos) who sustained a fracture. We assessed utilisation of post-acute care including rehabilitative and home care services, as well as informal care in persons with a hip, vertebral, or non-hip-non-vertebral fractures. RESULTS: use of rehabilitative and home care services was reported by 37.1% and 18.2% of men and women, respectively. Persons with hip fracture were more likely to report use of these services compared with persons with non-hip-non-vertebral fractures; those with vertebral fracture were less likely to report using these services. Use of informal care was reported by 47.2% of participants. Individuals with multiple fractures made more extensive use of post-acute resources compared with those with single fractures. CONCLUSIONS: use of post-acute care in individuals with fracture is extensive and the contribution of use of these resources to the overall burden of fractures cannot be ignored. Our findings have implications for future economic analyses and policy-making related to care of osteoporotic fractures.

Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study.

BACKGROUND: Fractures have largely been assessed by their impact on quality of life or health care costs. We conducted this study to evaluate the relation between fractures and mortality. METHODS: A total of 7753 randomly selected people (2187 men and 5566 women) aged 50 years and older from across Canada participated in a 5-year observational cohort study. Incident fractures were identified on the basis of validated self-report and were classified by type (vertebral, pelvic, forearm or wrist, rib, hip and "other"). We subdivided fracture groups by the year in which the fracture occurred during follow-up; those occurring in the fourth and fifth years were grouped together. We examined the relation between the time of the incident fracture and death. RESULTS: Compared with participants who had no fracture during follow-up, those who had a vertebral fracture in the second year were at increased risk of death (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1-6.6); also at risk were those who had a hip fracture during the first year (adjusted HR 3.2, 95% CI 1.4-7.4). Among women, the risk of death was increased for those with a vertebral fracture during the first year (adjusted HR 3.7, 95% CI 1.1-12.8) or the second year of follow-up (adjusted HR 3.2, 95% CI 1.2-8.1). The risk of death was also increased among women with hip fracture during the first year of follow-up (adjusted HR 3.0, 95% CI 1.0-8.7). INTERPRETATION: Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival.

Development and validation of the Fracture Risk Scale (FRS) that predicts fracture over a 1-year time period in institutionalised frail older people living in Canada: an electronic record-linked longitudinal cohort study.

OBJECTIVES: To develop and validate our Fracture Risk Scale (FRS) over a 1-year time period, using the long-term care (LTC) Resident Assessment Instrument Minimum Data Set Version 2.0 (RAI-MDS 2.0). DESIGN: A retrospective cohort study. SETTING: LTC homes in Ontario, Canada. PARTICIPANTS: Older adults who were admitted to LTC and received a RAI-MDS 2.0 admission assessment between 2006 and 2010. RESULTS: A total of 29 848 LTC residents were enrolled in the study. Of these 22 386 were included in the derivation dataset and 7462 individual were included in the validation dataset. Approximately 2/3 of the entire sample were women and 45% were 85 years of age or older. A total of 1553 (5.2%) fractures were reported over the 1-year time period. Of these, 959 (61.8%) were hip fractures. Following a hip fracture, 6.3% of individuals died in the emergency department or as an inpatient admission and did not return to their LTC home. Using decision tree analysis, our final outcome scale had eight risk levels of differentiation. The percentage of individuals with a hip fracture ranged from 0.6% (lowest risk level) to 12.6% (highest risk level). The area under the curve of the outcome scale was similar for the derivation (0.67) and validation (0.69) samples, and the scale exhibited a good level of consistency. CONCLUSIONS: Our FRS predicts hip fracture over a 1-year time period and should be used as an aid to support clinical decisions in the care planning of LTC residents. Future research should focus on the transformation of our scale to a Clinical Assessment Protocol and to assess the FRS in other healthcare settings.

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.

Osteoporosis prescribing in long-term care: impact of a provincial knowledge translation strategy.

This study described prescribing trends before and after implementing a provincial strategy aimed at improving osteoporosis and fracture prevention in Ontario long-term care (LTC) homes. Data were obtained from a pharmacy provider for 10 LTC homes in 2007 and 166 homes in 2012. We used weighted, multiple linear regression analyses to examine facility-level changes in vitamin D, calcium, and osteoporosis medication prescribing rates between 2007 and 2012. After five years, the estimated increase in vitamin D, calcium, and osteoporosis medication prescribing rates, respectively, was 38.2 per cent (95% confidence interval [CI]: 29.0, 47.3; p < .001), 4.0 per cent (95% CI: -3.9, 12.0; p = .318), and 0.2 per cent (95% CI: -3.3, 3.7; p = .91). Although the study could not assess causality, findings suggest that wide-scale knowledge translation activities successfully improved vitamin D prescribing rates, although ongoing efforts are needed to target homes with low uptake.

Successful knowledge translation intervention in long-term care: final results from the vitamin D and osteoporosis study (ViDOS) pilot cluster randomized controlled trial.

BACKGROUND: Few studies have systematically examined whether knowledge translation (KT) strategies can be successfully implemented within the long-term care (LTC) setting. In this study, we examined the effectiveness of a multifaceted, interdisciplinary KT intervention for improving the prescribing of vitamin D, calcium and osteoporosis medications over 12-months. METHODS: We conducted a pilot, cluster randomized controlled trial in 40 LTC homes (21 control; 19 intervention) in Ontario, Canada. LTC homes were eligible if they had more than one prescribing physician and received services from a large pharmacy provider. Participants were interdisciplinary care teams (physicians, nurses, consultant pharmacists, and other staff) who met quarterly. Intervention homes participated in three educational meetings over 12 months, including a standardized presentation led by expert opinion leaders, action planning for quality improvement, and audit and feedback review. Control homes did not receive any additional intervention. Resident-level prescribing and clinical outcomes were collected from the pharmacy database; data collectors and analysts were blinded. In addition to feasibility measures, study outcomes were the proportion of residents taking vitamin D (≥800 IU/daily; primary), calcium ≥500 mg/day and osteoporosis medications (high-risk residents) over 12 months. Data were analyzed using the generalized estimating equations technique accounting for clustering within the LTC homes. RESULTS: At baseline, 5,478 residents, mean age 84.4 (standard deviation (SD) 10.9), 71% female, resided in 40 LTC homes, mean size = 137 beds (SD 76.7). In the intention-to-treat analysis (21 control; 19 intervention clusters), the intervention resulted in a significantly greater increase in prescribing from baseline to 12 months between intervention versus control arms for vitamin D (odds ratio (OR) 1.82, 95% confidence interval (CI): 1.12, 2.96) and calcium (OR 1.33, 95% CI: 1.01, 1.74), but not for osteoporosis medications (OR 1.17, 95% CI: 0.91, 1.51). In secondary analyses, excluding seven nonparticipating intervention homes, ORs were 3.06 (95% CI: 2.18, 4.29), 1.57 (95% CI: 1.12, 2.21), 1.20 (95% CI: 0.90, 1.60) for vitamin D, calcium and osteoporosis medications, respectively. CONCLUSIONS: Our KT intervention significantly improved the prescribing of vitamin D and calcium and is a model that could potentially be applied to other areas requiring quality improvement. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01398527 . Registered: 19 July 2011.

Photochemical electron transfer reactions of tirapazamine.

The absorption and fluorescence spectra of 3-aminobenzo-1,2,4-triazine di-N-oxide (tirapazamine) have been recorded and exhibit a dependence on solvent that correlates with the Dimroth ET30 parameter. Time-dependent density functional theory calculations reveal that the transition of tirapazamine in the visible region is pi-->pi* in nature. The fluorescence lifetime is 98+/-2 ps in water. The fluorescence quantum yield is approximately 0.002 in water. The fluorescence of tirapazamine is efficiently quenched by electron donors via an electron-transfer process. Linear Stern-Volmer fluorescence quenching plots are observed with sodium azide, potassium thiocyanate, guanosine monophosphate and tryptophan (Trp) methyl ester hydrochloride. Guanosine monophosphate, tyrosine (Tyr) methyl ester hydrochloride and Trp methyl ester hydrochloride appear to quench the fluorescence at a rate greater than diffusion control implying that these substrates complex with tirapazamine in its ground state. This complexation was detected by absorption spectroscopy.

North American male reference population for speed of sound in bone at multiple skeletal sites.

Alternatives to dual-energy X-ray absorptiometry (DXA) have been sought to increase access to low-cost osteoporosis risk assessment. Early quantitative ultrasound (QUS) systems measured speed of sound (SOS) and broadband ultrasound attenuation (BUA) at the calcaneus, and these were demonstrated to be good predictors of hip fracture risk. Recent studies have demonstrated the usefulness of other peripheral sites to assess bone status. The Sunlight Omnisense (Sunlight Medical, Rehovot, Israel) is a portable, inexpensive QUS device capable of multiple-site SOS measurement. To provide a robust male reference database, 588 healthy Caucasian males aged 20-90 yr were recruited from 6 centers across North America. SOS measurements were taken at the distal 1/3 radius, proximal third phalanx, midshaft tibia, and fifth metatarsal. A female reference database has previously been collected at North American sites. The results indicate that SOS in males exhibits an age-related decline beginning in the fifth decade at the radius, phalanx, and metatarsal, whereas the tibial SOS remains nearly constant until the ninth decade. Although females reach a higher-peak SOS than males at most sites, SOS is higher in males at all sites after the sixth decade, as a result of a more gradual decline in SOS. Longitudinal monitoring of healthy men should be performed to confirm these cross-sectional results.

An interdisciplinary knowledge translation intervention in long-term care: study protocol for the vitamin D and osteoporosis study (ViDOS) pilot cluster randomized controlled trial.

BACKGROUND: Knowledge translation (KT) research in long-term care (LTC) is still in its early stages. This protocol describes the evaluation of a multifaceted, interdisciplinary KT intervention aimed at integrating evidence-based osteoporosis and fracture prevention strategies into LTC care processes. METHODS AND DESIGN: The Vitamin D and Osteoporosis Study (ViDOS) is underway in 40 LTC homes (n = 19 intervention, n = 21 control) across Ontario, Canada. The primary objectives of this study are to assess the feasibility of delivering the KT intervention, and clinically, to increase the percent of LTC residents prescribed ≥800 IU of vitamin D daily. Eligibility criteria are LTC homes that are serviced by our partner pharmacy provider and have more than one prescribing physician. The target audience within each LTC home is the Professional Advisory Committee (PAC), an interdisciplinary team who meets quarterly. The key elements of the intervention are three interactive educational sessions led by an expert opinion leader, action planning using a quality improvement cycle, audit and feedback reports, nominated internal champions, and reminders/point-of-care tools. Control homes do not receive any intervention, however both intervention and control homes received educational materials as part of the Ontario Osteoporosis Strategy. Primary outcomes are feasibility measures (recruitment, retention, attendance at educational sessions, action plan items identified and initiated, internal champions identified, performance reports provided and reviewed), and vitamin D (≥800 IU/daily) prescribing at 6 and 12 months. Secondary outcomes include the proportion of residents prescribed calcium supplements and osteoporosis medications, and falls and fractures. Qualitative methods will examine the experience of the LTC team with the KT intervention. Homes are centrally randomized to intervention and control groups in blocks of variable size using a computer generated allocation sequence. Randomization is stratified by home size and profit/nonprofit status. Prescribing data retrieval and analysis are performed by blinded personnel. DISCUSSION: Our study will contribute to an improved understanding of the feasibility and acceptability of a multifaceted intervention aimed at translating knowledge to LTC practitioners. Lessons learned from this study will be valuable in guiding future research and understanding the complexities of translating knowledge in LTC.

Removing cosmic ray features from Raman map data by a refined nearest neighbor comparison method as a precursor for chemometric analysis.

An algorithm to remove cosmic ray (CR) features from Raman spectra collected in mapping experiments using a charge-coupled device (CCD) is presented. Each spectrum is compared to spectra collected from adjacent points in space using correlation values. The most similar neighbor (MSN) spectrum is selected, offset, and used for identification of CRs. The offset values are defined in terms of the noise level for data with a low signal-to-noise ratio and in terms of the peak height for data with a high signal-to-noise ratio. Scaled intensity values of the MSN spectra are used for replacement of contaminated pixels, allowing for full recovery of underlying spectral features. The algorithm is applicable for any Raman map where the particle sizes within the analyzed mixture are larger than the sampling size or to any other data where the sampling is more frequent than the variation, e.g., time series or temperature profiles. Its application to several maps of pharmaceutical samples is discussed here. With an appropriate offset value for the MSN spectra, no misdetections occur, and all CRs more intense than the offset are removed, which includes the CRs that would have hampered subsequent chemometric analysis by methods such as principal component analysis (PCA).

Risk factors associated with incident clinical vertebral and nonvertebral fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study (CaMos).

Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.