Predicting Slow Walking Speed From a Pooled Cohort Analysis: Sarcopenia Definitions, Agreement, and Prevalence in Australia and New Zealand.

BACKGROUND: Recent operational definitions of sarcopenia have not been replicated and compared in Australia and New Zealand (ANZ) populations. We aimed to identify sarcopenia measures that discriminate ANZ adults with slow walking speed (<0.8 m/s) and determine the agreement between the Sarcopenia Definitions and Outcomes Consortium (SDOC) and revised European Working Group for Sarcopenia in Older People (EWGSOP2) operational definitions of sarcopenia. METHODS: Eight studies comprising 8 100 ANZ community-dwelling adults (mean age ± standard deviation, 62.0 ± 14.4 years) with walking speed, grip strength (GR), and lean mass data were combined. Replicating the SDOC methodology, 15 candidate variables were included in sex-stratified classification and regression tree models and receiver operating characteristic curves on a pooled cohort with complete data to identify variables and cut points discriminating slow walking speed (<0.8 m/s). Agreement and prevalence estimates were compared using Cohen's Kappa (CK). RESULTS: Receiver operating characteristic curves identified GR as the strongest variable for discriminating slow from normal walking speed in women (GR <20.50 kg, area under curve [AUC] = 0.68) and men (GR <31.05 kg, AUC = 0.64). Near-perfect agreement was found between the derived ANZ cut points and SDOC cut points (CK 0.8-1.0). Sarcopenia prevalence ranged from 1.5% (EWGSOP2) to 37.2% (SDOC) in women and 1.0% (EWGSOP2) to 9.1% (SDOC) in men, with no agreement (CK <0.2) between EWGSOP2 and SDOC. CONCLUSIONS: Grip strength is the primary discriminating characteristic for slow walking speed in ANZ women and men, consistent with findings from the SDOC. Sarcopenia Definitions and Outcomes Consortium and EWGSOP2 definitions showed no agreement suggesting these proposed definitions measure different characteristics and identify people with sarcopenia differently.

Secondary headaches - red and green flags and their significance for diagnostics.

A small percentage of patients suffer from a secondary headache syndrome. It is imperative that clinicians are able to differentiate primary headache syndromes from secondary headache syndromes, as failure to do so significantly worsens morbidity and mortality. Recent advances in our understanding of pathobiological mechanisms offer useful information on these enigmatic disorders. We now understand that the causes of secondary headache syndromes can vary significantly - these may be infectious, inflammatory, vascular, traumatic or structural in origin. A well-taken history and targeted physical examination coupled with appropriate investigations can enable these syndromes to be recognized consistently and thus allow their timely and appropriate treatment. Along with their epidemiology, some of their key characteristics shall thus be discussed in this review so as to aid the busy clinician at the bedside. Red flags including sudden onset, high pain intensity, pattern of change of a preexisting headache, focal neurological signs or seizure, systemic signs and precipitation by physical activity can guide the clinician to suspect a secondary headache. Importantly a preexisting headache is not an exclusion of a secondary headache - it might even be a predisposition in certain cases.

Mortality, falls and slow walking speed are predicted by different muscle strength and physical performance measures in women and men.

BACKGROUND: Different measures of muscle strength, physical performance and body size/composition are used in various sarcopenia definitions. This study investigated which baseline measures best predict incident mortality and falls, and prevalent slow walking speed in older women and men. MATERIALS AND METHODS: Data for 899 women (mean age±standard deviation, 68.7 ± 4.3 years) and 497 men (69.4 ± 3.9 years) from the Dubbo Osteoporosis Epidemiology Study 2, comprising sixty variables for muscle strength (quadriceps strength), physical performance (walking speed, timed up and go (TUG) test, sit to stand (STS) test), body size (weight, height, body mass index) and body composition (lean mass, body fat) were included. Sex-stratified Classification and Regression Tree (CART) analyses calculated baseline variable accuracy for predicting incident mortality and falls, and prevalent slow walking speed (<0.8 m/s). RESULTS: Over 14.5 years, 103/899 (11.5%) women and 96/497 (19.3%) men died, 345/899 (38.4%) women and 172/497 (34.6%) men had ≥1 fall, and 304/860 (35.3%) women and 172/461 (31.7%) had baseline slow walking speed (<0.8 m/s). CART models identified age and walking speed adjusted for height as the most important predictors for mortality in women, and quadriceps strength (with adjustments) as the most important predictor for mortality in men. In both sexes, STS (with adjustments) was the most important predictor for incident falls, and TUG test was the most important predictor for prevalent slow walking speed. Body composition measures were not important predictors for any outcome. CONCLUSIONS: Muscle strength and physical performance variables and cut points predict falls and mortality differently in women and men, suggesting targeted sex-specific application of selected measures may improve outcome prediction in older adults.

Integrating post-fracture care into the primary care setting (interFRACT): Protocol for a mixed-methods study to co-design a care program to improve rates of osteoporosis and fracture treatment.

INTRODUCTION: Despite evidence showing that timely diagnosis and appropriate pharmacological treatment of osteoporosis reduces subsequent fracture rates, osteoporosis remains significantly underdiagnosed and undertreated. The large and ongoing treatment gap for osteoporosis and associated fragility fractures could be addressed by considering systematic approaches for post-fracture care in the primary care setting. This study will develop the Integrating Post-Fracture Care into Primary Care (interFRACT) care program that aims to enhance diagnosis and treatment of osteoporosis and improve initiation and adherence to fracture prevention strategies for older adults in the primary care setting. METHODS AND ANALYSIS: This mixed-methods study will follow an established co-design approach that involves six steps; the first three aim to gain an understanding of the consumer experience and needs, while the latter three focus on how to improve that experience through design and action. This will include: development of a Stakeholder Advisory Committee to provide guidance on all aspects of study design, including implementation, evaluation and dissemination; interviews with primary care physicians to explore beliefs and attitudes towards osteoporosis and fracture treatment; interviews with consumers (older adults with a diagnosis of osteoporosis and/or fragility fracture) to identify current needs for osteoporosis treatment and fracture prevention; a series of co-design workshops to develop the components of the interFRACT care program based on published guidance and findings from interviews; and a feasibility study with primary care physicians to determine the usability and acceptability of the interFRACT care program. ETHICS AND DISSEMINATION: Ethical approval was obtained from Deakin University Human Research Ethics Committee (approval number: HEAG-H 56_2022). Study results will be published in peer-reviewed journals, presented at national and international conferences, and collated in reports for participating primary care practices.

Prevention of Osteoporotic Fractures in Residential Aged Care: Updated Consensus Recommendations.

Osteoporosis is underdiagnosed and undertreated in people living in Residential Aged Care Facilities (RACFs), even though aged-care residents are at greater risk of experiencing fractures than their community-dwelling counterparts. The first (2009) and second (2016) Consensus Conferences on the Treatment of Osteoporosis in RACFs in Australia addressed the prevention of falls and fractures in RACFs. A third Consensus Conference was held to review advances in the field of osteoporosis for people living in RACFs and to update current guidelines. The Conference was held virtually in October 2020 due to the COVID-19 pandemic. Attendance at the meeting was open to health practitioners (n = 116) (eg, general practitioners, geriatricians, rehabilitation specialists, endocrinologists, pharmacists, and physiotherapists) working in RACFs. Participants chose and/or were assigned to breakout groups to review the evidence and reach a consensus on the topic area assigned to the group, which was then presented to the entire group by a nominated spokesperson. Recommendations developed by breakout groups were discussed and voted on by all attending participants. This article updates the evidence for preventing falls and fractures and managing osteoporosis in older adults living in RACFs based on agreed outcomes from the group. We anticipate these updated recommendations will provide health practitioners with valuable guidance when practicing in RACFs.

Activation of the Protein Kinase R-Like Endoplasmic Reticulum Kinase (PERK) Pathway of the Unfolded Protein Response after Experimental Traumatic Brain Injury and Treatment with a PERK Inhibitor.

Neurodegeneration after traumatic brain injury (TBI) is increasingly recognized as a key factor contributing to poor chronic outcomes. Activation (i.e., phosphorylation) of the protein kinase R-like endoplasmic reticulum kinase (PERK) pathway has been implicated in neurodegenerative conditions with pathological similarities to TBI and may be a potential target to improve TBI outcomes. Here, we aimed to determine whether a moderate TBI would induce activation of the PERK pathway and whether treatment with the PERK inhibitor, GSK2606414, would improve TBI recovery. Male mice were administered a lateral fluid percussion injury (FPI) or sham injury and were euthanized at either 2 h, 24 h, or 1 week post-injury (n = 5 per injury group and time point) to assess changes in the PERK pathway. In the injured cortex, there was increased phosphorylated-PERK at 2 h post-FPI and increased phosphorylation of eukaryotic translation initiation factor α at 24 h post-FPI. We next examined the effect of acute treatment with GSK2606414 on pathological and behavioral outcomes at 4 weeks post-injury. Thus, there were a total of four groups: sham + VEH (n = 9); sham + GSK4606414 (n = 10); FPI + VEH (n = 9); and FPI + GSK2606414 (n = 9). GSK2606414 (50 mg/kg) or vehicle treatment was delivered by oral gavage beginning at 30 min post-injury, followed by two further treatments at 12-h increments. There were no significant effects of GSK2606414 on any of the outcomes assessed, which could be attributable to several reasons. For example, activation of PERK may not be a significant contributor to the neurological consequences 4 weeks post-FPI in mice. Further research is required to elucidate the role of the PERK pathway in TBI and whether interventions that target this pathway are beneficial.

Body composition reference ranges in community-dwelling adults using dual-energy X-ray absorptiometry: the Australian Body Composition (ABC) Study.

BACKGROUND: Reference ranges for lean mass (LM) and fat mass (FM) are essential in identifying soft tissue disorders; however, no such reference ranges exist for the most commonly used Hologic dual-energy X-ray absorptiometry (DXA) machine in Australia. METHODS: Cross-sectional study of community-dwelling adults (aged 18-88 years) who underwent a Hologic DXA scan at one of three commercialized densitometry centres in Australia. Age-specific and sex-specific percentile curves were generated for LM [LM, appendicular lean mass (ALM), ALM adjusted for height squared (ALM/h2 ), and ALM adjusted for body mass index (ALM/BMI)] and FM [FM, FM adjusted for height squared (FM/h2 ), appendicular fat mass, and android and gynoid fat] parameters using the LMS statistical method. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations below the young mean reference group (20-29 years) were also generated for LM parameters. RESULTS: A total of 15 479 community-dwelling adults (54% men) with a median age of 33 years (interquartile range: 28, 42) were included. LM, ALM, and ALM/h2 remained stable until age 50, after which these parameters started to decline in both sexes. Compared with age 50, median percentiles of LM, ALM, and ALM/h2 declined by -5.9 kg, -3.7 kg, and -0.86 kg/m2 in men and by -2.5 kg, -1.8 kg, and -0.10 kg/m2 in women at age 70, respectively. Adjusting ALM for BMI (rather than height squared) resulted in different trends, with ALM/BMI decreasing from as early as age 20. Compared with age 20, median percentiles of ALM/BMI at age 40 declined by -0.10 kg/kg/m2 in men and by -0.06 kg/kg/m2 in women; and at age 70, ALM/BMI declined by -0.25 kg/kg/m2 in men and by -0.20 kg/kg/m2 in women. Cutpoints equivalent to T-scores of -1, -2, and -2.5 standard deviations for ALM/BMI were 1.01, 0.86, and 0.77 kg/kg/m2 in men and 0.70, 0.59, and 0.53 kg/kg/m2 in women, respectively. All FM parameters progressively increased from age 20 and continued up until age 70. CONCLUSIONS: We developed reference ranges for LM and FM parameters from Hologic DXA machines in a large cohort of Australian adults, which will assist researchers and clinicians in identifying soft tissue disorders such as obesity, sarcopenia, and cachexia.

Sarcopenia Definitions and Outcomes Consortium (SDOC) Criteria are Strongly Associated With Malnutrition, Depression, Falls, and Fractures in High-Risk Older Persons.

OBJECTIVES: Sarcopenia Definitions and Outcomes Consortium (SDOC) provides cut-points based on muscle weakness (low grip strength) and slowness (poor gait speed) for low-risk populations; however, it is unknown if these criteria apply to high-risk populations. We examined the association between SDOC criteria and important health status indicators in high-risk older persons. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 356 community-dwelling older persons (median age: 79 years, interquartile range: 73, 83; 75.2% women) attending a falls and fractures clinic in Melbourne, Australia. METHODS: Grip strength (hydraulic dynamometer) and gait speed (over 4 m) were used to define sarcopenia using SDOC cut-points. Health measures included falls (past 1 year) and fractures (past 5 years) by self-report, and malnutrition, depression, balance confidence, fear of falling, static balance (limits of stability), dynamic balance (Four-Square Step Test), and body composition [body mass index and lean mass, fat mass, and bone density (via dual-energy x-ray absorptiometry)] were assessed using validated procedures. Fasting vitamin D and parathyroid hormone concentrations were measured by immunoassays. Participants were categorized as nonsarcopenic or sarcopenic based on the SDOC cut-points, and multivariate models were used to examine the association between sarcopenia and health status indicators while adjusting for confounding factors. RESULTS: After adjusting for covariates, sarcopenic older persons (n = 162, 45.5%) were positively associated with malnutrition [odds ratio (OR) 3.21, 95% confidence interval (CI) 1.63, 6.32], depression (OR 4.11, 95% CI 2.31, 7.29), fear of falling (OR 1.08, 95% CI 1.06, 1.10) as well as recurrent (2 or more) falls (OR 1.62, 95% CI 1.01, 2.59) and fractures (OR 2.26, 95% CI 1.17, 4.36), and negatively associated with poor balance confidence (OR 0.96, 95% CI 0.95, 0.97) (P < .05 vs nonsarcopenic). CONCLUSIONS AND IMPLICATIONS: SDOC criteria are strongly associated with important health status indicators in high-risk older persons, which strengthens the clinical utility of the SDOC in these populations.