Alpha1-antitrypsin deficiency in Greece: Focus on rare variants.

PURPOSE: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. AIM: to investigate genotype and clinical profile of Greeks with AATD. METHODS: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. RESULTS: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). CONCLUSION: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.

Geographic variation in bone mineral density and prevalent fractures in the Canadian longitudinal study on aging.

Awareness of the prevalence of osteoporosis and fractures across jurisdictions can guide the development of local preventive programs and healthcare policies. We observed geographical variations in total hip bone mineral density and in the prevalence of major osteoporotic fractures across Canadian provinces, which persisted after adjusting for important covariates. PURPOSE: We aimed to describe sex-specific total hip bone mineral density (aBMD) and prevalent major osteoporotic fractures (MOF) variation between Canadian provinces. METHODS: We used baseline data from 21,227 Canadians (10,716 women, 10,511 men) aged 50-85 years in the Canadian Longitudinal Study on Aging (CLSA; baseline: 2012-2015). Linear and logistic regression models were used to examine associations between province of residence and total hip aBMD and self-reported MOF, stratified by sex. CLSA sampling weights were used to generate the prevalence and regression estimates. RESULTS: The mean (SD) age of participants was 63.9 (9.1) years. The mean body mass index (kg/m2) was lowest in British Columbia (27.4 [5.0]) and highest in Newfoundland and Labrador (28.8 [5.3]). Women and men from British Columbia had the lowest mean total hip aBMD and the lowest prevalence of MOF. Alberta had the highest proportion of participants reporting recent falls (12.0%), and Manitoba (8.4%) the fewest (p-value=0.002). Linear regression analyses demonstrated significant differences in total hip aBMD: women and men from British Columbia and Alberta, and women from Manitoba and Nova Scotia had lower adjusted total hip aBMD than Ontario (p-values<0.02). Adjusted odds ratios (95% confidence intervals, CI) for prevalent MOF were significantly lower in women from British Columbia (0.47 [95% CI: 0.32; 0.69]) and Quebec (0.68 [95% CI: 0.48; 0.97]) and in men from British Columbia (0.40 [95% CI:0.22; 0.71]) compared to Ontario (p-values<0.03). Results were similar when adjusting for physical performance measures and when restricting the analyses to participants who reported White race/ethnicity. CONCLUSION: Geographical variations in total hip aBMD and in the prevalence of MOF between provinces persisted after adjusting for important covariates which suggests an association with unmeasured individual and environmental factors.

International consensus on the non-pharmacological and non-surgical management of osteoporotic vertebral fractures.

We identified a knowledge gap in the non-pharmacological and non-surgical management of osteoporotic vertebral fractures. MAIN RESULTS: This international consensus process established multidisciplinary biopsychosocial recommendations on pain, nutrition, safe movement, and exercise for individuals with acute and chronic vertebral fractures. SIGNIFICANCE: These recommendations will guide clinical practice and inform interventions for future research. PURPOSE: To establish international consensus on recommendations for the non-pharmacological and non-surgical management of osteoporotic vertebral fractures. METHODS: We adopted a five-step modified Delphi consensus process: (1) literature search and content analysis, (2) creation of the survey, (3) selection of the expert panel, (4) first round of the rating process, and (5) second round of the rating process. The first round included 49 statements and eight open-ended questions; the second round included 30 statements. Panelists were asked to rate their agreement with each of the statements using a 9-point scale, with the option to provide further comments. Consensus for each statement was determined by counting the number of panelists whose rating was outside the 3-point region containing the median. RESULTS: We invited 76 people with degree in medicine, physiotherapy, kinesiology, and experience in the management of osteoporotic vertebral; 31 (41%) and 27 (36%) experts agreed to participate to the first and the second round, respectively. The mean percentage agreement after the first and second rounds was 76.6% ± 16.0% and 90.7% ± 6.5%, respectively. We established consensus on recommendations on pain, early satiety, weight loss, bracing, safe movement, and exercise for individuals with acute and chronic vertebral fractures. CONCLUSION: Our international consensus provides multidisciplinary biopsychosocial recommendations to guide the management of osteoporotic vertebral fractures and inform interventions for future research.

Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group.

The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. INTRODUCTION: The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. METHODS: The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation's Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. RESULTS AND CONCLUSION: The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.

The global approach to rehabilitation following an osteoporotic fragility fracture: A review of the rehabilitation working group of the International Osteoporosis Foundation (IOF) committee of scientific advisors.

PURPOSE: To conduct a review of the current state of the evidence for rehabilitation strategies post-fragility fracture. METHODS: Narrative review conducted by the Rehabilitation Working Group of the International Osteoporosis Foundation Committee of Scientific Advisors characterizing the range of rehabilitation modalities instrumental for the management of fragility fractures. RESULTS: Multi-modal exercise post-fragility fracture to the spine and hip is strongly recommended to reduce pain, improve physical function, and improve quality of life. Outpatient physiotherapy post-hip fracture has a stronger evidence base than outpatient physiotherapy post-vertebral fracture. Appropriate nutritional care after fragility fracture provides a large range of improvement in morbidity and mortality. Education increases understanding of osteoporosis which in turn increases utilization of other rehabilitation services. Education may improve other health outcomes such as pain and increase a patient's ability for self-advocacy. CONCLUSION: Rehabilitation interventions are inter-reliant, and research investigating the interaction of exercise, nutrition, and other multi-modal therapies may increase the relevance of rehabilitation research to clinical care.

Use of an electronic medical record dashboard to identify gaps in osteoporosis care.

Using an electronic medical record (EMR)-based dashboard, this study explored osteoporosis care gaps in primary care. Eighty-four physicians shared their practice activities related to bone mineral density testing, 10-year fracture risk calculation and treatment for those at high risk. Significant gaps in fracture risk calculation and osteoporosis management were identified. PURPOSE: To identify care gaps in osteoporosis management focusing on Canadian clinical practice guidelines (CPG) related to bone mineral density (BMD) testing, 10-year fracture risk calculation and treatment for those at high risk. METHODS: The ADVANTAGE OP EMR tool consists of an interactive algorithm to facilitate assessment and management of fracture risk using CPG. The FRAX® and Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tools were embedded to facilitate 10-year fracture risk calculation. Physicians managed patients as clinically indicated but with EMR reminders of guideline recommendations; participants shared practice level data on management activities after 18-month use of the tool. RESULTS: Eighty-four physicians (54%) of 154 who agreed to participate in this study shared their aggregate practice activities. Across all practices, there were 171,310 adult patients, 40 years of age and older, of whom 17,214 (10%) were at elevated risk for fracture. Sixty-two percent of patients potentially at elevated risk for fractures did not have BMD testing completed; most common reasons for this were intention to order BMD later (48%), physician belief that BMD was not required (15%) and patient refusal (20%). For patients with BMD completed, fracture risk was calculated in 29%; 19% were at high risk, of whom 37% were not treated with osteoporosis medications as recommended by CPG. CONCLUSION: Despite access to CPG and fracture risk calculators through the ADVANTAGE OP EMR tool, significant gaps remain in fracture risk calculation and osteoporosis management. Additional strategies are needed to address this clinical inertia among family physicians.

Exploring changes in bone mass in individuals with a chronic spinal cord injury.

People experience rapid bone loss shortly after a spinal cord injury (SCI), but the long-term bone changes are yet to be confirmed. This study showed that trabecular bone may have reached a steady state, whereas cortical bone continued to decline in people with a chronic SCI (mean time post injury: 15.5 ± 10 years). INTRODUCTION: (1) To explore changes in bone [primary measure: trabecular volumetric bone mineral density (vBMD); secondary measures: cortical vBMD, cortical thickness, cortical cross-sectional area (CSA), and polar moment of inertia] over 2 years in individuals with a chronic spinal cord injury (SCI). (2) To explore whether muscle density changes were potential correlates of the observed bone changes. METHODS: This study is a secondary data analysis of a prospective, observational study involving 70 people with a chronic SCI (≥ 2 years post injury). The study included 4 strata of participants with diverse impairments: (1) Paraplegia (T1-T12) motor complete American Spinal Injury Association Impairment Scale (AIS) A/B (n = 23), (2) Paraplegia motor incomplete AIS C/D (n = 11), (3) Tetraplegia (C2-C8) AIS A/B (n = 22), and (4) Tetraplegia AIS C/D (n = 14). Peripheral quantitative computed tomography scans were taken at the 4% (distal tibia), 38% (diaphyseal tibia), and 66% (muscle cross-sectional area) tibia sites by measuring from the distal to proximal tibia starting at the inferior border of the medial malleolus. The tibia sites were assessed annually over a span of 2 years. Comparisons were made using a paired-samples t test and simple linear regression was used to adjust for sex, time post injury, and bisphosphonate use. RESULTS: We observed no changes in trabecular vBMD at the 4% tibia site, but there was a statistically significant decline in cortical vBMD, cortical thickness, and CSA at the 38% tibia site. Changes in muscle density were not associated with the decreases observed in cortical bone. CONCLUSION: Our findings suggest that individuals with chronic SCI (mean duration of injury: 15.5 ± 10 years) may have reached a plateau in bone loss with respect to trabecular bone, but cortical bone loss can continue well into the chronic stages.

Differences in fracture prevalence and in bone mineral density between Chinese and White Canadians: the Canadian Multicentre Osteoporosis Study (CaMos).

Fracture determinants differ between Canadians of Chinese and White descent, the former constituting the second largest visible minority group in Canada. The results of this study support the importance of characterizing bone health predictors in Canadians of different ethnicity to improve population-specific fracture prevention and treatment strategies. PURPOSE: We aimed to compare clinical risk factors, bone mineral density, prevalence of osteoporosis, and fractures between Chinese and White Canadians to identify ethnicity-specific risks. METHODS: We studied 236 Chinese and 8945 White Canadians aged 25+ years from the Canadian Multicentre Osteoporosis Study (CaMos). The prevalence of osteoporosis using ethnicity-specific peak bone mass (PBM), and of prior and incident low trauma fractures were assessed and compared between groups. Linear regressions, adjusting for age and anthropometric measures, were used to examine the association between baseline and 5-year changes in BMD and ethnicity. RESULTS: Chinese participants had shorter stature, lower BMI, and lower rate of falls than White participants. Adjusted models showed no significant differences in baseline BMD between ethnic groups except in younger men where total hip BMD was 0.059 g/cm2 (0.009; 0.108) lower in Chinese. Adjusted 5-year BMD change at lumbar spine was higher in older Chinese women and men compared with Whites. When using Chinese-specific PBM, the prevalence of osteoporosis in Chinese women was 2-fold lower than when using that of White women The prevalence of fractures was higher in White women compared with Chinese with differences up to 14.5% (95% CI 9.2; 19.7) and 10.5% (95% CI 4.5-16.4) in older White men. Incident fractures were rare in young Chinese compared with White participants and not different in the older groups. CONCLUSION: Our results support the importance of characterizing bone strength predictors in Chinese Canadians and the development of ethnicity-specific fracture prediction and prevention strategies.

Describing the resource utilisation and costs associated withvertebral fractures: the Build Better Bones with Exercise (B3E) Pilot Trial.

This analysis examined costs/resources of 141 women with vertebral fractures, randomised to a home exercise programme or control group. Total, mean costs and the incremental cost-effectiveness ratio (ICER) were calculated. Quality of life was collected. Cost drivers were caregiver time, medications and adverse events (AEs). Results show adding an exercise programme may reduce the risk of AEs. INTRODUCTION: This exploratory economic analysis examined the health resource utilisation and costs experienced by women with vertebral fractures, and explored the effects of home exercise on those costs. METHODS: Women ≥ 65 years with one or more X-ray-confirmed vertebral fractures were randomised 1:1 to a 12-month home exercise programme or equal attention control group. Clinical and health system resources were collected during monthly phone calls and daily diaries completed by participants. Intervention costs were included. Unit costs were applied to health system resources. Quality of life (QoL) information was collected via EQ-5D-5L at baseline, 6 and 12 months. RESULTS: One hundred and forty-one women were randomised. Overall total costs (CAD 2018) were $664,923 (intervention) and $614,033 (control), respectively. The top three cost drivers were caregiver time ($250,269 and $240,811), medications ($151,000 and $122,145) and AEs ($58,807 and $71,981). The mean cost per intervention participant of $9365 ± $9988 was higher compared with the mean cost per control participant of $8772 ± $9718. The mean EQ-5D index score was higher for the intervention participants (0.81 ± 0.11) compared with that of controls (0.79 ± 0.13). The differences in quality-adjusted life year (QALY) (0.02) and mean cost ($593) were used to calculate the ICER of $29,650. CONCLUSIONS: Women with osteoporosis with a previous fracture experience a number of resources and associated costs that impact their care and quality of life. Caregiver time, medications and AEs are the biggest cost drivers for this population. The next steps would be to expand this feasibility study with more participants, longer-term follow-up and more regional variability.

Correction to: Comparison of the clinical effectiveness and safety between the use of denosumab vs bisphosphonates in renal transplant patients.

The original version of this article, published on 03 January 2020 contained a mistake. An author's name was misspelled.

Testing a theoretical model of imminent fracture risk in elderly women: an observational cohort analysis of the Canadian Multicentre Osteoporosis Study.

We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health. INTRODUCTION: This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk. METHODS: Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI). RESULTS: The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ2(172) = 1122.10 < .001, RMSEA = .03, TLI = .99, CFI = .99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p < .001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p < .001). CONCLUSIONS: We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds.

Comparison of the clinical effectiveness and safety between the use of denosumab vs bisphosphonates in renal transplant patients.

A retrospective chart review was conducted on 85 renal transplant patients aged 19-88 years, treated with denosumab or bisphosphonate therapy. Bone densitometry measures were compared between treatment groups at baseline; at years 1, 2, and 3; and at final follow-up (average of 3.4 years). Both bisphosphonate and denosumab treatments increased lumbar spine bone density; however, the effect of denosumab was greater compared with that of bisphosphonate treatment. Denosumab treatment increased femoral neck BMD, whereas bisphosphonate treatment had a mean decrease in femoral neck BMD at final follow-up. Thus, our study provides evidence for the efficacy of denosumab treatment in renal transplant patients. Caution around hypocalcemia is warranted. We recommend more prospective studies to analyze the effects of long-term antiresorptive therapy in patients with a renal transplant. INTRODUCTION: To compare the clinical effectiveness and safety between the use of denosumab and bisphosphonates on bone density and incidence of adverse events in renal transplant patients. METHODS: A retrospective chart review was conducted on 85 renal transplant patients aged 19-88 years, treated with denosumab or bisphosphonate therapy. Bone densitometry measures were compared between treatment groups at baseline; years 1, 2, and 3; and at final follow-up (average of 3.4 years). RESULTS: Absolute change in lumbar spine and femoral neck BMD over the treatment period was 0.029 ± 0.075 g/cm2 and - 0.003 ± 0.064 g/cm2, respectively, in the bisphosphonate group. Absolute change in lumbar spine and femoral neck BMD at final follow-up was 0.072 ± 0.094 g/cm2 and 0.025 ± 0.063 g/cm2, respectively, in the denosumab group. Denosumab resulted in significantly greater increases in lumbar spine BMD (0.045 g/cm2 greater in the denosumab group). Similarly, the absolute change in BMD at the femoral neck was 0.022 g/cm2 greater in the denosumab group as compared with the bisphosphonate group. The denosumab group had one event of severe hypocalcemia following first injection and one report of hospitalized pneumonia. No serious adverse events were reported in the bisphosphonate group. CONCLUSIONS: Both treatments increased lumbar spine BMD; however, the effect of denosumab was greater compared with that of bisphosphonate treatment. Our study provides evidence for the efficacy of denosumab treatment in renal transplant patients. Caution around hypocalcemia is warranted. We recommend more prospective studies to analyze the effects of long-term antiresorptive therapy in patients with a renal transplant.

Pharmacological treatment of stable COPD: need for a simplified approach.

Chronic obstructive pulmonary disease (COPD) is one of the most common diseases worldwide. Although different guidelines regarding therapeutic algorithms exist, the most widely adopted approach is the one suggested by the Global Initiative in Chronic Obstructive Lung Disease in which patients are stratified according to their dyspnea severity and their exacerbation history during the previous year. This combined assessment of COPD, which takes into consideration all aforementioned characteristics of COPD patients as well as the number of blood eosinophils, results in a proposed therapeutic algorithm which is complex and hard to memorize. This complexity is probable one of the causes that most health care professionals are not adherent to the guidelines when treating COPD patients. Here, we propose a simplified therapeutic algorithm for the treatment of COPD patients taking into consideration the current evidence on the use of bronchodilators and inhaled corticosteroids.

Meanings and feelings of (Im)mobility in later life: Case study insights from a 'New Mobilities' perspective.

Understandings of mobility and immobility shape research and responses to late life. Yet, the underlying assumptions about mobility often remain fixed on ideas of function and physical ability. The 'new mobilities' paradigm shifts this analysis by focusing on the importance and experience of mobility as a thing in itself rather than a means to an end, and to the complex enactments that operate across a range of relationships, settings, sites, and contexts. This paper provides insight from an embedded case study method comprised of fifteen exploratory interviews with older people at three social locations, including 5 individuals considered 'frail', 5 people who are aging with a disability, and 5 older people who self-identify as 'active'. Considered together and in contrast, the findings from these three distinct but related embedded case sites, viewed from a 'new mobilities' perspective, can help to understand (im)mobility as an embodied experience that is situated within and across social and political contexts, and can explicate how relations of power enhance the mobility of some, and the immobility of others. We conclude that the 'new mobilities' approach introduces ideas to overcome limitations of distance, movement, and place, and in doing so, serves to redefine what it means to be mobile while aging.

Persistence at 24 months with denosumab among postmenopausal women with osteoporosis: results of a prospective cohort study.

Persistence with prescribed medications for chronic diseases is important; however, persistence with osteoporosis treatments is historically poor. In this prospective cohort study of postmenopausal women treated for osteoporosis in real-world clinical practice settings in the USA and Canada, 24-month persistence with denosumab was 58%. PURPOSE: Patients who persist with their prescribed osteoporosis treatment have increased bone mineral density (BMD) and reduced risk of fracture. Twelve-month persistence with denosumab in routine clinical practice is as high as 95%, but there are limited data on longer-term persistence with denosumab in this setting. METHODS: This single-arm, prospective, cohort study evaluated 24-month persistence with denosumab administered every 6 months in postmenopausal women receiving treatment for osteoporosis in real-world clinical practice in the USA and Canada. Endpoints and analyses included the percentage of patients who persist with denosumab at 24 months (greater than or equal to four injections with a gap between injections of no more than 6 months plus 8 weeks), the total number of injections received by each patient, changes in BMD in persistent patients, and the incidence of serious adverse events (SAEs) and fractures. RESULTS: Among 935 enrolled patients, 24-month persistence was 58% (50% in US patients and 75% in Canadian patients). A majority of patients received at least four injections over the observation period (62% of US patients and 81% of Canadian patients). Among patients who were persistent at 24 months and who had a baseline, 12-month, and 24-month DXA scan, mean BMD increased from baseline to 24 months by 7.8% at the lumbar spine and 2.1% at the femoral neck. SAEs and fractures were reported for 122 (13.0%) patients and 54 (5.8%) patients, respectively. CONCLUSIONS: Persistence with denosumab for 24 months yields improvement in BMD among postmenopausal women with osteoporosis treated in routine clinical practice in the USA and Canada.

Build better bones with exercise (B3E pilot trial): results of a feasibility study of a multicenter randomized controlled trial of 12 months of home exercise in older women with vertebral fracture.

We pilot-tested a trial of home exercise on individuals with osteoporosis and spine fracture. Our target enrollment was met, though it took longer than expected. Participants stayed in the study and completed the exercise program with no safety concerns. Future trials should expand the inclusion criteria and consider other changes. PURPOSE: Osteoporotic fragility fractures create a substantial human and economic burden. There have been calls for a large randomized controlled trial examining the effect of exercise on fracture incidence. The B3E pilot trial was designed to evaluate the feasibility of a large trial examining the effects of home exercise on individuals at high risk of fracture. METHODS: Community-dwelling women ≥ 65 years with radiographically confirmed vertebral compression fractures were recruited at seven sites in Canada and Australia. We randomized participants in a 1:1 ratio to a 12-month home exercise program or equal attention control group, both delivered by a physiotherapist (PT). Participants received six PT home visits in addition to monthly phone calls from the PT and a blinded research assistant. The primary feasibility outcomes of the study were recruitment rate (20 per site in 1 year), retention rate (75% completion), and intervention adherence rate (60% of weeks meeting exercise goals). Secondary outcomes included falls, fractures and adverse events. RESULTS: One hundred forty-one participants were recruited; an average of 20 per site, though most sites took longer than anticipated. Retention and adherence met the criteria for success: 92% of participants completed the study; average adherence was 66%. The intervention group did not differ significantly in the number of falls (IRR 0.97, 95% CI 0.58 to 1.63) or fragility fractures (OR 1.11, 95% CI 0.60 to 2.05) compared to the control group. There were 18 serious adverse events in the intervention group and 12 in the control group. CONCLUSION: An RCT of home exercise in women with vertebral fractures is feasible but recruitment was a challenge. Suggestions are made for the conduct of future trials.

The use of local anesthesia to perform lower limb revascularization in the fragile patient with critical limb ischemia.

Patients with critical limb ischemia are usually compromised, frequently making administration of general or regional anesthesia problematic. We treated 3 fragile patients presenting contraindications to undertake traditional anesthetic techniques for lower limb revascularization, in whom local anesthesia with conscious sedation was used to complete the operation. An axillo-bifemoral, a unilateral axillo-femoral and a femoro-femoral bypass were performed. Procedure was uneventful in all three cases despite the coexistence of specific surgical challenges (distal anastomosis at the profunda in two cases, redo surgery and scarred groin in the third). Surgical revascularization under local anesthesia may be considered in selected high risk patients.

"Left to my own devices, I don't know": using theory and patient-reported barriers to move from physical activity recommendations to practice.

Knowledge exchange with community-dwelling individuals across Ontario revealed barriers to implementation of physical activity recommendations that reflected capability, opportunity, and motivation; barriers unique to individuals with osteoporosis include fear of fracturing, trust in providers, and knowledge of exercise terminology. Using the Behaviour Change Wheel, we identified interventions (training, education, modeling) and policy categories (communication/marketing, guidelines, service provision). INTRODUCTION: Physical activity recommendations exist for individuals with osteoporosis; however, to change behavior, we must address barriers and facilitators to their implementation. The purposes of this project are (1) to identify barriers to and facilitators of uptake of disease-specific physical activity recommendations (2) to use the findings to identify behavior change strategies using the Behaviour Change Wheel (BCW). METHODS: Focus groups and semi-structured interviews were conducted with community-dwelling individuals attending osteoporosis-related programs or education sessions in Ontario. They were stratified by geographic area, urban/rural, and gender, and transcribed verbatim. Two researchers coded data and identified emerging themes. Using the Behaviour Change Wheel framework, themes were categorized into capability, opportunity, and motivation, and interventions were identified. RESULTS: Two hundred forty community-dwelling individuals across Ontario participated (mean ± SD age = 72 ± 8.28). Barriers were as follows: capability: disease-related symptoms hinder exercise and physical activity participation, lack of exercise-related knowledge, low exercise self-efficacy; opportunity: access to exercise programs that meet needs and preferences, limited resources and time, physical activity norms and preferences; motivation: incentives to exercise, fear of fracturing, trust in exercise providers. Interventions selected were training, education, and modeling. Policy categories selected were communication/marketing, guidelines, and service provision. CONCLUSIONS: Barriers unique to individuals with osteoporosis included the following: lack of knowledge on key exercise concepts, fear of fracturing, and trust in providers. Behavior change techniques may need tailoring to gender, age, or presence of comorbid conditions.

Measuring frailty in clinical practice: a comparison of physical frailty assessment methods in a geriatric out-patient clinic.

BACKGROUND: The objectives of this study were to determine: 1) the prevalence of frailty using Fried's phenotype method and the Short Performance Physical Battery (SPPB), 2) agreement between frailty assessment methods, 3) the feasibility of assessing frailty using Fried's phenotype method and the SPPB. METHODS: This cross-sectional study was conducted at a geriatric out-patient clinic in Hamilton, Canada. A research assistant conducted all frailty assessments. Patients were classified as non-frail, pre-frail or frail according to Fried's phenotype method and the SPPB. Agreement among methods is reported using the Cohen kappa statistic (standard error). Feasibility data included the percent of eligible participants agreeing to attempt the frailty assessments (criterion for feasibility: ≥90% of patients agreeing to the frailty assessment), equipment required, and safety considerations. A p-value of <0.05 is considered significant. RESULTS: A total of 110 participants (92%) and 109 participants (91%) agreed to attempt Fried's phenotype method and SPPB, respectively. No adverse events occurred during any assessments. According to Fried's phenotype method, the prevalence of frailty and pre-frailty was 35% and 56%, respectively, and according to the SPPB, the prevalence of frailty and pre-frailty was 50% and 35%, respectively. There was fair to moderate agreement between methods for determining which participants were frail (0.488 [0.082], p < 0.001) and pre-frail (0.272 [0.084], p = 0.002). CONCLUSIONS: Frailty and pre-frailty are common in this geriatric outpatient population, and there is fair to moderate agreement between Fried's phenotype method and the SPPB. Over 90% of the patients who were eligible for the study agreed to attempt the frailty assessments, demonstrating that according to our feasibility criteria, frailty can be assessed in this patient population. Assessing frailty may help clinicians identify high-risk patients and tailor interventions based on baseline frailty characteristics.