COVID-19 in patients with lung cancer.

BACKGROUND: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 (COVID-19) outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic. PATIENTS AND METHODS: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n = 102) at a single center from 12 March 2020 to 6 May 2020. Thresholds of severity were defined a priori as hospitalization, intensive care unit/intubation/do not intubate ([ICU/intubation/DNI] a composite metric of severe disease), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. Human leukocyte antigen (HLA) alleles were inferred from MSK-IMPACT (n = 46) and compared with controls with lung cancer and no known non-COVID-19 (n = 5166). RESULTS: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease [odds ratio for severe COVID-19 2.9, 95% confidence interval 1.07-9.44 comparing the median (23.5 pack-years) to never-smoker and 3.87, 95% confidence interval 1.35-9.68, respectively]. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. Human leukocyte antigen supertypes were generally similar in mild or severe cases of COVID-19 compared with non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. CONCLUSION: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.

Changes in spinal bone density, back muscle size, and visceral adipose tissue and their interaction following a multi-component exercise program in older men: secondary analysis of an 18-month randomized controlled trial.

In middle-aged and older men, an 18-month multi-component exercise program improved spinal trabecular BMD, paraspinal, and psoas muscle cross-sectional area (CSA) but not visceral adipose tissue (VAT). However, changes in both muscle and VAT CSA were associated with changes in spinal BMD, independent of the exercise intervention. INTRODUCTION: In older men, we previously reported that a multi-component exercise program improved lumbar spine (LS) trabecular volumetric BMD (Tb.vBMD) compared with no exercise. This study aimed to investigate the following: (1) the effect of the exercise program on paraspinal and psoas (back) muscle CSA and VAT, and 2) if any exercise-related changes in muscle CSA and/or VAT were associated with changes in spinal BMD. METHODS: Men (n = 180) aged 50-79 years were randomized to an exercise or no-exercise group. Exercise involved high-intensity progressive resistance training (60-85% max) with weight-bearing impact exercise (3 days/week) for 18 months. Quantitative computed tomography was used to assess L1-L3 Tb.vBMD, paraspinal, and psoas muscle CSA and VAT. RESULTS: Exercise resulted in a 2.6% ((95% CI, 1.1, 4.1), P < 0.01) net gain in back muscle CSA, but no effect on VAT (-1.6% (95% CI, -7.3, 4.2)) relative to no exercise. Robust regression indicated that percentage changes in Tb.vBMD were positively associated with changes (expressed as z-scores) in back muscle CSA in both the exercise (beta (ß)-coefficient = 1.9, 95% CI 0.5, 3.2, P = 0.007) and no-exercise (ß = 2.6, 95% CI, 1.1, 4.1, P = 0.001) group, and negatively with the changes in VAT (ß = -2.0, 95% CI -3.3, -0.7, P = 0.003) in the exercise only group. There were no group differences in the slopes for the muscle-bone or VAT-bone relationships. Regression analysis (pooled data) revealed that back muscle CSA and VAT were independent predictors of the change in Tb.vBMD, explaining 14% of the variance. CONCLUSION: A multi-component exercise program in middle-aged and older men improved spinal BMD and back muscle size but not visceral fat. However, changes in back muscle size and VAT were associated with the changes in spinal BMD, independent of exercise. TRIAL REGISTRATION: ACTRN 12617001224314, 22/08/2017 retrospectively registered.

Utility of four sarcopenia criteria for the prediction of falls-related hospitalization in older Australian women.

Numerous sarcopenia definitions are not associated with increased falls-related hospitalization risk over 5 years to 9.5 years in older community-dwelling Australian women. Measures of muscle strength and physical function, but not appendicular lean mass (measured by dual-energy X-ray absorptiometry) may help discriminate the risk of falls-related hospitalization. INTRODUCTION: The aim of this prospective, population-based cohort study of 903 Caucasian-Australian women (mean age 79.9 ± 2.6 years) was to compare the clinical utility of four sarcopenia definitions for the prediction of falls-related hospitalization over 9.5 years. METHODS: The four definitions were the United States Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP), and modified FNIH (AUS-POPF) and EWGSOP (AUS-POPE) definitions using Australian population-specific cut points (< 2 SD below the mean of young healthy Australian women). Components of sarcopenia including muscle strength, physical function, and appendicular lean mass (ALM) were quantified using hand grip strength, timed-up-and-go (TUG), and dual-energy X-ray absorptiometry (DXA), respectively. Incident 9.5-year falls-related hospitalization were captured by linked data. RESULTS: Baseline prevalence of sarcopenia according to FNIH (9.4%), EWGSOP (24.1%), AUS-POPF (12.0%), and AUS-POPE (10.7%) differed substantially. Sarcopenia did not increase the relative hazard ratio (HR) for falls-related hospitalization before or after adjustment for age (aHR): FNIH aHR 1.00 95%CI (0.69-1.47), EWGSOP aHR 1.20 95%CI (0.93-1.54), AUS-POPF aHR 0.96 95%CI (0.68-1.35), and AUS-POPE aHR 1.33 95%CI (0.94-1.88). When examining individual components of sarcopenia, only muscle strength and physical function but not ALM (adjusted for height2 or BMI) were associated with falls-related hospitalization. CONCLUSION: Current definitions of sarcopenia were not associated with falls-related hospitalization risk in this cohort of community-dwelling older Australian women. Finally, measures of muscle strength and physical function, but not ALM (measured by DXA) may help discriminate the risk of falls-related hospitalization.

The effect of exercise on bone mineral density in adult cancer survivors: a systematic review and meta-analysis.

PURPOSE: Certain cancer treatments are associated with bone loss and increased fracture risk. Weight-bearing impact exercise, resistance training or the combination, are recommended to preserve or improve bone mineral density (BMD) inhealthy older adults, but their efficacy in cancer survivors is less well understood. The aim of this systematic review with meta-analysis of randomised control trials (RCT) was to review the evidence regarding the role of exercise to counteract cancer treatment-induced bone loss. METHODS: Four databases were searched systematically with 12 RCTs of at least 6-month duration investigating the effects of exercise on BMD compared to a control group in adult cancer survivors identified. RESULTS: Meta-analysis was completed using available data from six studies enrolling 814 participants, with lumbar spine, femoral neck and/or total hip BMD as the primary outcome measures. Overall, there was no significant benefit of exercise compared to controls on BMD at the lumbar spine (0.0071 g/cm , 95% CI -0.0002 to 0.0145, p = 0.057), femoral neck (0.0044 g/cm , 95% CI -0.0005 to 0.0093, p = 0.077), or total hip (0.0024 g/cm , 95% CI -0.0038 to 0.0086, p = 0.443). Subgroup analysis revealed a positive effect on lumbar spine BMD in three studies implementing a combined resistance and impact exercise intervention (0.015 g/cm , 95% CI 0.003 to 0.028, p = 0.019). CONCLUSIONS: From the evidence available, exercise may not be sufficient to improve bone health in cancer survivors, but given the heterogeneity in the participant characteristics and several exercise programs which may not have been designed to specifically optimise bone health, these findings should be interpreted with caution.

Association of sitting time and breaks in sitting with muscle mass, strength, function, and inflammation in community-dwelling older adults.

The mechanisms through which excessive sitting time impacts health are important to understand. This study found that each hour of sitting per day was not associated with physical function, although associations with poor body composition were observed. Reducing sitting time for improved weight management in older adults needs further exploration. INTRODUCTION: To examine the association of sitting time and breaks in sitting time with muscle mass, strength, function, and inflammation in older Australians. METHODS: Data from the thigh-worn activPAL3™ monitor (7-day continuous wear) was used to derive time spent sitting (hours) and total number of sit-stand transitions per day. Body composition (dual energy X-ray absorptiometry), lower-body muscle strength, function (timed up-and-go [TUG], 4-m gait speed, four square step test, 30-second sit-to-stand), and serum inflammatory markers (interleukin-[IL-6], IL-8, IL-10, tumor necrosis factor-alpha [TNF-α], and adiponectin) were measured. Multiple regression analyses, adjusted for age, sex, ethnicity, education, employment status, marital status, number of prescription medications, smoking status, vitamin D, and stepping time, were used to assess the associations. RESULTS: Data from 123 community-dwelling older adults (aged 65-84 years, 63% female) were used. Total daily sitting time was associated with lower percentage lean mass (ß [95%CI], - 1.70% [- 2.30, - 1.10]) and higher total body fat mass (2.92 kg [1.94, 3.30]). More frequent breaks in sitting time were associated with a 45% reduced risk of having pre-sarcopenia (OR = 0.55; 95% CI 0.34, 0.91; model 1), defined as appendicular lean mass divided by BMI. No significant associations were observed for sitting time or breaks in sitting with measures of muscle strength, function, or inflammation. CONCLUSION: In older community-dwelling adults, greater sitting time was associated with a lower percentage lean mass, while more frequent breaks in sitting time were associated with lower odds of having pre-sarcopenia. This suggests that reducing sedentary time and introducing frequent breaks in sedentary time may be beneficial for improving body composition in healthy older adults.

Exercise and nutritional approaches to prevent frail bones, falls and fractures: an update.

Osteoporosis (low bone strength) and sarcopenia (low muscle mass, strength and/or impaired function) often co-exist (hence the term 'sarco-osteoporosis') and have similar health consequences with regard to disability, falls, frailty and fractures. Exercise and adequate nutrition, particularly with regard to vitamin D, calcium and protein, are key lifestyle approaches that can simultaneously optimize bone, muscle and functional outcomes in older people, if they are individually tailored and appropriately prescribed in terms of the type and dose. Not all forms of exercise are equally effective for optimizing musculoskeletal health. Regular walking alone has little or no effect on bone or muscle. Traditional progressive resistance training (PRT) is effective for improving muscle mass, size and strength, but it has mixed effects on muscle function and falls which may be due to the common prescription of slow and controlled movement patterns. At present, targeted multi-modal programs incorporating traditional and high-velocity PRT, weight-bearing impact exercises and challenging balance/mobility activities appear to be most effective for optimizing musculoskeletal health and function. Reducing and breaking up sitting time may also help attenuate muscle loss. There is also evidence to support an interaction between exercise and various nutritional factors, particularly protein and some multi-nutrient supplements, on muscle and bone health in the elderly. This review summary provides an overview of the latest evidence with regard to the optimal type and dose of exercise and the role of various nutritional factors for preventing bone and muscle loss and improving functional capacity in older people.

Feasibility of a multi-modal exercise program on cognition in older adults with Type 2 diabetes - a pilot randomised controlled trial.

BACKGROUND: Type 2 Diabetes (T2D) is associated with increased risk of dementia. We aimed to determine the feasibility of a randomised controlled trial (RCT) examining the efficacy of exercise on cognition and brain structure in people with T2D. METHODS: A 6-month pilot parallel RCT of a progressive aerobic- and resistance-training program versus a gentle movement control group in people with T2D aged 50-75 years (n = 50) at the University of Tasmania, Australia. Assessors were blinded to group allocation. Brain volume (total, white matter, hippocampus), cortical thickness and white matter microstructure (fractional anisotrophy and mean diffusivity) were measured using magnetic resonance imaging, and cognition using a battery of neuropsychological tests. Study design was assessed by any changes (during the pilot or recommended) to the protocol, recruitment by numbers screened and time to enrol 50 participants; randomisation by similarity of characteristics in groups at baseline, adherence by exercise class attendance; safety by number and description of adverse events and retention by numbers withdrawn. RESULTS: The mean age of participants was 66.2 (SD 4.9) years and 48% were women. There were no changes to the design during the study. A total of 114 people were screened for eligibility, with 50 participants with T2D enrolled over 8 months. Forty-seven participants (94%) completed the study (23 of 24 controls; 24 of 26 in the intervention group). Baseline characteristics were reasonably balanced between groups. Exercise class attendance was 79% for the intervention and 75% for the control group. There were 6 serious adverse events assessed as not or unlikely to be due to the intervention. Effect sizes for each outcome variable are provided. CONCLUSION: This study supports the feasibility of a large scale RCT to test the benefits of multi-modal exercise to prevent cognitive decline in people with T2D. Design changes to the future trial are provided. TRIAL REGISTRATION: ANZCTR 12614000222640 ; Registered 3/3/2014; First participant enrolled 26/6/2014, study screening commenced 1/9/2014; Australian and New Zealand Clinical Trial Registry.

Association between serum concentration of 25-hydroxyvitamin D and the risk of hip arthroplasty for osteoarthritis: result from a prospective cohort study.

OBJECTIVES: There is ongoing debate regarding the optimal serum concentrations of 25-hydroxy-vitamin D for musculoskeletal health, including osteoarthritis (OA). The aim of this prospective cohort study was to determine whether serum 25-hydroxy-vitamin D concentrations were associated with the risk of hip arthroplasty for OA. DESIGN: This study examined 9135 participants from the Australian Diabetes, Obesity and Lifestyle Study who had serum 25-hydroxy-vitamin D measured in 1999-2000 and were aged ≥40 years at the commencement of arthroplasty data collection. The incidence of hip arthroplasty for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over an average 9.1 (standard deviation (SD) 2.7) years of follow-up, 201 hip arthroplasties for OA were identified (males n = 90; females n = 111). In males, a one-standard-deviation increase in 25-hydroxy-vitamin D was associated with a 25% increased incidence (HR 1.25, 95% CI 1.02-1.56), with a dose response relationship evident by quartiles of 25-hydroxy-vitamin D concentration (P for trend 0.04). These results were independent of age, body mass index (BMI), ethnicity, smoking status, physical activity, season of blood collection, latitude, hypertension and diabetes, area level disadvantage or after excluding those with extreme low 25-hydroxy-vitamin D concentrations. No significant association was observed in women (HR 1.10, 95% CI 0.87, 1.39). CONCLUSIONS: Increasing serum 25-hydroxy-vitamin D concentrations were associated with an increased risk of hip arthroplasty for OA in males, while no significant association was observed in females. The mechanism for the association warrants further investigation.

Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial.

UNLABELLED: Vitamin D can improve muscle function and reduce falls, but whether it can strengthen neural connections within the brain and nervous system is not known. This 10-week randomised controlled trial indicates that treatment with 2,000 IU/day vitamin D3 does not significantly alter neuroplasticity relative to placebo in older adults. INTRODUCTION: The purpose of this study was to examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults. METHODS: This was a 10-week double-blinded, placebo-controlled randomised trial in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25-60 nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and paired-pulse transcranial magnetic stimulation applied over the motor cortex was used to assess changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as measures of corticospinal excitability and inhibition respectively, by recording electromyography (EMG) responses to stimulation from the wrist extensors. Changes in muscle strength, stair climbing power, gait (timed-up-and-go), dynamic balance (four square step test), serum 25(OH)D and BDNF concentrations were also measured. RESULTS: After 10 weeks, mean 25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no change in the placebo group. The vitamin D group experienced a significant 8-11% increase in muscle strength and a reduction in cortical excitability (MEP amplitude) and SICI relative to baseline (all P < 0.05), but these changes were not significantly different from placebo. There was no effect of vitamin D on muscle power, function or BDNF. CONCLUSIONS: Daily supplementation with 2,000 IU vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to placebo, but the finding that vitamin D treatment alone was associated with a decrease in corticospinal excitability and intracortical inhibition warrants further investigation as this suggests that it may improve the efficacy of neural transmission within the corticospinal pathway.

Associations between sedentary behaviour and body composition, muscle function and sarcopenia in community-dwelling older adults.

SUMMARY: While previous studies have reported detrimental associations of sedentary behaviours with cardiometabolic disorders and mortality, in this study, we report that higher levels of sitting time were associated with a greater risk of sarcopenia, with increased television (TV) viewing negatively associated with lean mass, independent of physical activity. INTRODUCTION: Sedentary behaviour has been linked to cardiometabolic disorders and mortality, but little is known about its effects on musculoskeletal health and function. This study investigated the relationship between total sitting and TV viewing time on sarcopenia and its determinants (muscle mass, strength and function) in older adults. METHODS: This cross-sectional study included 162 community-dwelling men and women aged 60 to 86 years who had complete assessment of total body and regional lean mass (LM) and fat mass (dual-energy X-ray absorptiometry (DXA)), lower limb muscle strength, power and functional performance. Sarcopenia was defined as the lowest sex-specific quartile for relative appendicular LM plus muscle strength and/or gait speed. Total sitting and TV viewing time were self-reported using a validated questionnaire. A sitting fragmentation ratio, as an index of breaks in sitting time, was calculated as the number of sitting bouts divided by total sitting time. RESULTS: Greater overall sitting time was associated with an increased risk of sarcopenia; for each 1-h increment, the risk increased by 33% [odds ratio 1.33 (95% confidence interval (CI) 1.05, 1.68)], independent of physical activity and other lifestyle and confounding factors. TV viewing time was associated with lower total body and leg LM after adjusting for various confounders and fat mass. There were no associations between total sitting or TV viewing time or the fragmentation ratio with any other measure. CONCLUSION: Higher levels of sedentary behaviour in older adults were associated with reduced muscle mass and an increased risk of sarcopenia in community-dwelling older adults, independent of physical activity.

Mid-femoral and mid-tibial muscle cross-sectional area as predictors of tibial bone strength in middle-aged and older men.

While it is widely acknowledged that bones adapt to the site-specific prevalent loading environment, reasonable ways to estimate skeletal loads are not necessarily available. For long bone shafts, muscles acting to bend the bone may provide a more appropriate surrogate of the loading than muscles expected to cause compressive loads. Thus, the aim of this study was to investigate whether mid-thigh muscle cross-sectional area (CSA) was a better predictor of tibial mid-shaft bone strength than mid-tibia muscle CSA in middle aged and older men. 181 Caucasian men aged 50-79 years (mean±SD; 61±7 years) participated in this study. Mid-femoral and mid-tibial bone traits cortical area, density weighted polar moment of area and muscle CSA [cm(2)] were assessed with computed tomography. Tibial bone traits were positively associated with both the mid-femur (r=0.44 to 0.46, P<0.001) and the mid-tibia muscle CSA (r=0.35 to 0.37, P<0.001). Multivariate regression analysis, adjusting for age, weight, physical activity and femoral length, indicated that mid-femur muscle CSA predicted tibial mid-shaft bone strength indices better than mid-tibia muscle CSA. In conclusion, the association between a given skeletal site and functionally adjacent muscles may provide a meaningful probe of the site-specific effect of loading on bone.

Effects of a Multi-component, Resistance-Based Exercise Program Combined with Additional Lean Red Meat on Health-Related Quality of Life in Older Adults: Secondary Analysis of a 6-Month Randomized Controlled Trial.

OBJECTIVES: To assess whether consumption of lean red meat on three exercise training days per week can promote greater improvements than exercise alone in health-related quality of life (HR-QoL) in community-dwelling older adults. DESIGN: This study is a secondary analysis from a 6 month, two-arm, parallel randomized controlled trial conducted in 2014 and 2015. SETTING: Community-dwelling older adults living in metropolitan Melbourne, Australia. PARTICIPANTS: One hundred and fifty-four men and women aged ≥65 years. INTERVENTION: All participants were enrolled in a multi-component, resistance-based exercise program (3 d/week) and randomly allocated to either a group asked to consume lean red meat (2x80g cooked servings/day) on each of the three training days (Ex+Meat, n=77) or a control group asked to consume one serving of carbohydrates (1/2 cup rice/pasta or 1 medium potato; Ex+C, n=77). MEASUREMENTS: HR-QoL was assessed using the Short-Form (SF)-36 health survey. RESULTS: Overall 62% of the participants were female, the mean age was 70.7 years (range 65 to 84 years), approximately 67% of participants were classified as either overweight or obese, and the average number of chronic conditions was two. A total of 145 participants (94%) completed the study. Mean baseline HR-QoL scores were comparable to the mean for the Australian population [Global HR-QoL (mean ± SD): Ex+Meat, 49.99 ± 6.57; Ex+C, 50.49 ± 5.27]. General Linear Mixed Models examining within and between group changes over time revealed that after 6 months, there were no within-group changes in either Ex+Meat or Ex+C nor any between-group differences for any measure of HR-QoL, with the exception that the mental health subscale improved in Ex+C versus Ex+Meat [net difference for change, -2.32 (95% CI), -4.73, 0.09, P=0.048] after adjusting for relevant covariates and the physical function subscale improved in Ex+Meat relative to baseline [mean change (95% CI), 1.88 (0.37, 3.39), P=0.011]. CONCLUSION: A multi-component resistance-based training program performed with and without the provision of lean red meat in line with current Australian dietary guidelines on each of the three training days, did not improve HR-QoL in healthy community-dwelling older adults.

Delivery of Home-Based Exercise Interventions in Older Adults Facilitated by Amazon Alexa: A 12-week Feasibility Trial.

OBJECTIVES: To evaluate the feasibility of using voice-controlled intelligent personal assistants (VIPAs) to remotely deliver and monitor an individually-tailored, home-based exercise program to older adults living independently and alone. DESIGN: 12-week, prospective single-arm feasibility study. SETTING: Community residences. PARTICIPANTS: 15 adults aged 60 to 89 years living alone. INTERVENTION: All participants were prescribed home-based muscle strengthening, weight-bearing impact and balance exercises, increasing from two to four 10-minute sessions per day over 12 weeks. Sessions were delivered using VIPAs (Amazon Alexa Echo Show 5; "Alexa") and a novel software program ("Buddy Link"). The program was individualized by an exercise physiologist based on participant voice responses to Alexa questions. MEASUREMENTS: Study outcomes were feasibility (rate of retention, adherence, and adverse events), usability (System Usability Scale) and changes to quality of life (European Quality of Life Scale), and lower-extremity function (30 second sit-to-stand test). RESULTS: All 15 participants (mean age, 70.3 years) completed the study (retention 100%). Mean adherence to the exercise program was 115% (i.e., collectively all participants were prescribed 8640 exercises but completed 9944 exercises) with no adverse events reported to be related to the intervention and usability scored as above average (75/100). Other outcomes did not significantly change across the 12-week follow-up (all P>0.05). CONCLUSIONS: In this feasibility study of community-dwelling older adults living alone, a home-based exercise program delivered and monitored remotely by an exercise physiologist using VIPAs was safe and feasible.

Screening, Diagnosis and Management of Sarcopenia and Frailty in Hospitalized Older Adults: Recommendations from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Expert Working Group.

Sarcopenia and frailty are highly prevalent conditions in older hospitalized patients, which are associated with a myriad of adverse clinical outcomes. This paper, prepared by a multidisciplinary expert working group from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR), provides an up-to-date overview of current evidence and recommendations based on a narrative review of the literature for the screening, diagnosis, and management of sarcopenia and frailty in older patients within the hospital setting. It also includes suggestions on potential pathways to implement change to encourage widespread adoption of these evidence-informed recommendations within hospital settings. The expert working group concluded there was insufficient evidence to support any specific screening tool for sarcopenia and recommends an assessment of probable sarcopenia/sarcopenia using established criteria for all older (≥65 years) hospitalized patients or in younger patients with conditions (e.g., comorbidities) that may increase their risk of sarcopenia. Diagnosis of probable sarcopenia should be based on an assessment of low muscle strength (grip strength or five times sit-to-stand) with sarcopenia diagnosis including low muscle mass quantified from dual energy X-ray absorptiometry, bioelectrical impedance analysis or in the absence of diagnostic devices, calf circumference as a proxy measure. Severe sarcopenia is represented by the addition of impaired physical performance (slow gait speed). All patients with probable sarcopenia or sarcopenia should be investigated for causes (e.g., chronic/acute disease or malnutrition), and treated accordingly. For frailty, it is recommended that all hospitalized patients aged 70 years and older be screened using a validated tool [Clinical Frailty Scale (CFS), Hospital Frailty Risk Score, the FRAIL scale or the Frailty Index]. Patients screened as positive for frailty should undergo further clinical assessment using the Frailty Phenotype, Frailty Index or information collected from a Comprehensive Geriatric Assessment (CGA). All patients identified as frail should receive follow up by a health practitioner(s) for an individualized care plan. To treat older hospitalized patients with probable sarcopenia, sarcopenia, or frailty, it is recommended that a structured and supervised multi-component exercise program incorporating elements of resistance (muscle strengthening), challenging balance, and functional mobility training be prescribed as early as possible combined with nutritional support to optimize energy and protein intake and correct any deficiencies. There is insufficient evidence to recommend pharmacological agents for the treatment of sarcopenia or frailty. Finally, to facilitate integration of these recommendations into hospital settings organization-wide approaches are needed, with the Spread and Sustain framework recommended to facilitate organizational culture change, with the help of 'champions' to drive these changes. A multidisciplinary team approach incorporating awareness and education initiatives for healthcare professionals is recommended to ensure that screening, diagnosis and management approaches for sarcopenia and frailty are embedded and sustained within hospital settings. Finally, patients and caregivers' education should be integrated into the care pathway to facilitate adherence to prescribed management approaches for sarcopenia and frailty.

The calcium scare--what would Austin Bradford Hill have thought?

UNLABELLED: Detailed consideration of the suggested association between calcium supplementation and heart attacks has revealed weakness in the evidence which make the hypothesis highly implausible. INTRODUCTION: The aim of this study was to evaluate the strength of the evidence that calcium supplementation increases the risk of myocardial infarction. METHODS: This study used critical examination of a meta-analysis of the effects of calcium supplements on heart attacks in five prospective trials on 8,016 men and women, and consideration of related publications by the same author. RESULTS: The meta-analysis was found to be subject to several limitations including non-adherence to the clinical protocol, multiple endpoint testing and failure to correctly adjust for endpoint ascertainment. The main risk factors for myocardial infarction were not available for 65% of the participants, and none of the trials had cardiovascular disease as its primary endpoint. There were more overweight participants, more subjects on thyroxine and more men on calcium than on placebo. In particular, over 65% of all the heart attacks were self-reported. When the evidence was considered in the light of Austin Bradford Hill's six main criteria for disease causation, it was found not to be biologically plausible or strong or to reflect a dose-response relationship or to be consistent or to reflect the relationship between the trends in calcium supplementation and heart attacks in the community or to have been confirmed by experiment. The addition of a more recent trial on 1,460 women over 5 years reduced the relative risk to 1.23 (P = 0.0695). CONCLUSION: Present evidence that calcium supplementation increases heart attacks is too weak to justify a change in prescribing habits.

An open source approach for regional cortical bone mineral density analysis.

OBJECTIVE: Cortical porosity, particularly at the endocortical region, is recognised to play a central role in the pathogenesis of bone fragility. Therefore, the purpose of this study was to: 1) demonstrate how cortical volumetric BMD (vBMD) distribution can be analysed from (p)QCT images and 2) highlight the clinical significance of assessing regional density distribution of cortical bone. METHODS: We used pQCT to compare mid-tibial cortical volumetric BMD distribution of 20 young (age 24(SD2) years, mass 77(11) kg, height 178(6) cm) and 25 elderly (72(4) years, 75(9) kg, 172(5) cm) men. Radial and polar cortical vBMD distributions were analysed using a custom built open source analysis tool which allowed the cortex to be divided into three concentric cortical divisions and in 36 cortical sectors originating from the centroid of the bone. RESULTS: Mean vBMD did not differ between the groups (1135(16) vs. 1130(28) mg/cm, P = 0.696). In contrast, there was a significant age-group by radial division interaction for radial cortical vBMD (P<0.001). CONCLUSIONS: The proposed analysis method for analysing cortical bone density distribution of pQCT images was effective for detecting regional differences in cortical density between young and elderly men, which would have been missed by just looking at mean vBMD values.

Association between hyperglycaemia and fracture risk in non-diabetic middle-aged and older Australians: a national, population-based prospective study (AusDiab).

SUMMARY: The association between pre-diabetes and fracture risk remains unclear. In this large cohort of middle-aged and older Australian men and women without diabetes, elevated 2-h plasma glucose and pre-diabetes were associated with a reduced 5-year risk of low trauma and all fractures in women, independently of BMI, fasting insulin and other lifestyle factors. INTRODUCTION: We aimed to (1) examine associations between fasting and 2-h plasma glucose (FPG and 2-h PG), fasting insulin and risk of low trauma and all fractures in non-diabetic adults and (2) compare fracture risk between adults with pre-diabetes (impaired glucose tolerance or impaired fasting glucose) and those with normal glucose tolerance (NGT). METHODS: Six thousand two hundred fifty-five non-diabetic men and women aged ≥40 years with NGT (n = 4,855) and pre-diabetes (n = 1,400) were followed for 5 years in the AusDiab Study. Fractures were self-reported. RESULTS: Five hundred thirty-nine participants suffered at least one fracture (368 women, 171 men), of which the majority (318) occurred after a low-energy trauma (258 women, 60 men). In women, a 2-h PG ≥ 7.2 mmol/L (highest quartile) was associated with a decreased risk of low trauma and all fractures independent of age and BMI [OR (95% CI) for low trauma fractures, 0.59 (0.40-0.88)], but also fasting insulin, smoking, physical activity, history of fracture, dietary calcium and alcohol intake or menopausal status. There was no effect of 2-h PG on fracture risk in men [OR (95% CI), 1.39 (0.60-3.26)] or any relationship between fracture risk and quartiles of FPG or insulin in either sex. Compared to women with NGT, those with pre-diabetes had a reduced risk of fracture [OR (95% CI) for all fractures, 0.70 (0.52-0.95); for low trauma fractures, 0.75 (0.53-1.05)]. CONCLUSION: Elevated 2-h PG levels and pre-diabetes were inversely associated with low trauma and/or all fractures in non-diabetic women, independent of BMI and fasting insulin levels.

Effects of a multi-component exercise program and calcium-vitamin-D3-fortified milk on bone mineral density in older men: a randomised controlled trial.

SUMMARY: We examined the independent and combined effects of a multi-component exercise program and calcium-vitamin-D(3)-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium-vitamin D(3) did not enhance the response in this group of older well-nourished men. INTRODUCTION: This 12-month randomised controlled trial assessed whether calcium-vitamin-D(3)-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men. METHODS: Men (n = 180) aged 50-79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D(3). Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed. RESULTS: There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p < 0.001); lean mass (0.6 kg, p < 0.05) and muscle strength (20-52%, p < 0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4-1.5% increase in all treatment groups relative to controls (all p < 0.01). There were no main effects of fortified milk at any skeletal site. CONCLUSION: A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium-vitamin D(3) did not enhance the osteogenic response.

Relationship between indices of adiposity obtained by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in pre-pubertal children.

BACKGROUND/AIM: The study investigated the relationship between indices of adiposity measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) in pre-pubertal children. SUBJECTS AND METHODS: DXA-derived per cent body fat (%BF) was measured in 284 boys and 288 girls, aged 7-10 years. Cross-sections of the forearm (n=427) and lower leg (n=560) were obtained by pQCT to measure total cross-sectional area of the limb (Total CSA), Muscle CSA, Fat CSA, %Fat CSA (Fat CSA/Total CSAx100) and muscle density. RESULTS: Peripheral QCT-derived %Fat CSA in the forearm and lower leg correlated strongly with DXA-derived %BF (r=0.83-0.89, p<0.01) in both boys and girls. However, forearm and lower leg %Fat CSA were higher than whole body %BF by 5% and 10%, respectively. A better prediction of whole-body %BF was achieved by including %Fat CSA, muscle density and height into a hierarchical regression model. Using sex-specific regression equations, 87.7% of the boys and 83.7% of the girls had a predicted %BF within 3% units of the %BF obtained by DXA. CONCLUSION: In pre-pubertal children, pQCT measures of adiposity are strongly associated with whole-body per cent body fat. This reproducible method could be an alternative technique to estimate body composition in this population.

Establishing an Operational Definition of Sarcopenia in Australia and New Zealand: Delphi Method Based Consensus Statement.

BACKGROUND: Globally there are several operational definitions for sarcopenia, complicating clinical and research applications. OBJECTIVE: The objective of the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Task Force on Diagnostic Criteria for Sarcopenia was to reach consensus on the operational definition of sarcopenia for regional use by clinicians and researchers. METHOD: A four-Phase modified Delphi process was undertaken in which 24 individuals with expertise or a recognised interest in sarcopenia from different fields across Australia and New Zealand were invited to be Task Force members. An initial face-to-face meeting was held in Adelaide, South Australia, in November 2017, followed by two subsequent online Phases conducted by electronic surveys. A final Phase was used to approve the final statements. Responses were analysed using a pre-specified strategy. The level of agreement required for consensus was 80%. RESULTS: In Phase 2, 94.1% of Task Force respondents voted in favour of adopting an existing operational definition of sarcopenia. In Phase 3, 94.4% of respondents voted in favour of adopting the European Working Group on Sarcopenia in Older People (EWGSOP) definition as the operational definition for sarcopenia in Australia and New Zealand. CONCLUSION: With consensus achieved, the ANZSSFR will adopt, promote and validate the EWGSOP operational definition of sarcopenia for use by clinicians and researchers in Australia and New Zealand.