Thigh Muscle Composition and Its Relationship to Functional Recovery Post Hip Fracture Over Time and Between Sexes.

BACKGROUND: Computed tomography (CT)-scan measures of muscle composition may be associated with recovery post hip fracture. METHODS: In an ancillary study to Baltimore Hip Studies Seventh cohort, older adults were evaluated at 2 and 6 months post hip fracture. CT-scan measures of muscle were acquired at 2 months. Short Physical Performance Battery (SPPB) was measured at 2 and 6 months. Generalized estimating equations were used to model the association of muscle measures and physical function, adjusting for age, sex, body mass index, and time postfracture. RESULTS: Seventy-one older adults (52% males, age 79.6 ± 7.3 years) were included. At 2-months, males had greater thigh cross-sectional area (CSA, p < .0001) and less low-density muscle (p = .047), and intermuscular adipose tissue (p = .007) than females on the side of the fracture, while females performed better on the SPPB (p = .05). Muscle measures on the fractured side were associated with function at 2 months in both sexes. Participants with the lowest tertile of muscle CSA difference at 2-months, indicating greater symmetry in CSA between limbs, performed better than the other 2 tertiles at 6-months. Males performed worse in functional measures at baseline and did not recover as well as females (p = .02). CONCLUSION: CT-scan measures of muscle CSA and fatty infiltration were associated with function at 2-months post hip fracture and with improvement in function by 6 months. Observed sex differences in these associations suggest that rehabilitation strategies may need to be adapted by sex after hip fracture.

Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project).

OBJECTIVE: To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. DESIGN: Evaluator blinded, randomised controlled trial. SETTING: 16 clinical sites across 11 European countries, January 2016 to 31 October 2019. PARTICIPANTS: 1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls). INTERVENTIONS: The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months. MAIN OUTCOME MEASURES: The primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes. RESULTS: Mean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; P<0.001) and 1.0 point (95% confidence interval 0.5 to 1.6 points; P<0.001) in favour of the multicomponent intervention at 24 and 36 months, respectively. The decline in handgrip strength at 24 months was smaller in women assigned to the multicomponent intervention than to control (0.9 kg, 95% confidence interval 0.1 to 1.6 kg; P=0.028). Women in the multicomponent intervention arm lost 0.24 kg and 0.49 kg less appendicular lean mass than controls at 24 months (95% confidence interval 0.10 to 0.39 kg; P<0.001) and 36 months (0.26 to 0.73 kg; P<0.001), respectively. Serious adverse events occurred in 237/605 (39.2%) participants assigned to the multicomponent intervention and 216/600 (36.0%) controls (risk ratio 1.09, 95% confidence interval 0.94 to 1.26). In participants with SPPB scores of 8 or 9, mobility disability occurred in 46/155 (29.7%) in the multicomponent intervention and 38/159 (23.9%) controls (hazard ratio 1.25, 95% confidence interval 0.79 to 1.95; P=0.34). CONCLUSIONS: A multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people. TRIAL REGISTRATION: ClinicalTrials.gov NCT02582138.

Sex Differences in Recovery Across Multiple Domains Among Older Adults With Hip Fracture.

BACKGROUND: Hip fractures are a public health problem among older adults, but most research on recovery after hip fracture has been limited to females. With growing numbers of hip fractures among males, it is important to determine how recovery outcomes may differ between the sexes. METHODS: 168 males and 171 females were enrolled within 15 days of hospitalization with follow-up visits at 2, 6, and 12 months postadmission to assess changes in disability, physical performance, cognition, depressive symptoms, body composition, and strength, and all-cause mortality. Generalized estimating equations examined whether males and females followed identical outcome recovery assessed by the change in each outcome. RESULTS: The mean age at fracture was similar for males (80.4) and females (81.4), and males had more comorbidities (2.5 vs 1.6) than females. Males were significantly more likely to die over 12 months (hazard ratio 2.89, 95% confidence interval: 1.56-5.34). Changes in outcomes were significantly different between males and females for disability, gait speed, and depressive symptoms (p < .05). Both sexes improved from baseline to 6 months for these measures, but only males continued to improve between 6 and 12 months. There were baseline differences for most body composition measures and strength; however, there were no significant differences in change by sex. CONCLUSIONS: Findings confirm that males have higher mortality but suggest that male survivors have continued functional recovery over the 12 months compared to females. Research is needed to determine the underlying causes of these sex differences for developing future prognostic information and rehabilitative interventions.

Bimagrumab vs Optimized Standard of Care for Treatment of Sarcopenia in Community-Dwelling Older Adults: A Randomized Clinical Trial.

Importance: The potential benefit of novel skeletal muscle anabolic agents to improve physical function in people with sarcopenia and other muscle wasting diseases is unknown. Objective: To confirm the safety and efficacy of bimagrumab plus the new standard of care on skeletal muscle mass, strength, and physical function compared with standard of care alone in community-dwelling older adults with sarcopenia. Design, Setting, and Participants: This double-blind, placebo-controlled, randomized clinical trial was conducted at 38 sites in 13 countries among community-dwelling men and women aged 70 years and older meeting gait speed and skeletal muscle criteria for sarcopenia. The study was conducted from December 2014 to June 2018, and analyses were conducted from August to November 2018. Interventions: Bimagrumab 700 mg or placebo monthly for 6 months with adequate diet and home-based exercise. Main Outcomes and Measures: The primary outcome was the change in Short Physical Performance Battery (SPPB) score after 24 weeks of treatment. Secondary outcomes included 6-minute walk distance, usual gait speed, handgrip strength, lean body mass, fat body mass, and standard safety parameters. Results: A total of 180 participants were recruited, with 113 randomized to bimagrumab and 67 randomized to placebo. Among these, 159 participants (88.3%; mean [SD] age, 79.1 [5.3] years; 109 [60.6%] women) completed the study. The mean SPPB score increased by a mean of 1.34 (95% CI, 0.90 to 1.77) with bimagrumab vs 1.03 (95% CI, 0.53 to 1.52) with placebo (P = .13); 6-minute walk distance increased by a mean of 24.60 (95% CI, 7.65 to 41.56) m with bimagrumab vs 14.30 (95% CI, -4.64 to 33.23) m with placebo (P = .16); and gait speed increased by a mean of 0.14 (95% CI, 0.09 to 0.18) m/s with bimagrumab vs 0.11 (95% CI, 0.05 to 0.16) m/s with placebo (P = .16). Bimagrumab was safe and well-tolerated and increased lean body mass by 7% (95% CI, 6% to 8%) vs 1% (95% CI, 0% to 2%) with placebo, resulting in difference of 6% (95% CI, 4% to 7%) (P < .001). Conclusions and Relevance: This randomized clinical trial found no significant difference between participants treated with bimagrumab vs placebo among older adults with sarcopenia who had 6 months of adequate nutrition and light exercise, with physical function improving in both groups. Bimagrumab treatment was safe, well-tolerated, increased lean body mass, and decreased fat body mass. The effects of sarcopenia, an increasing cause of disability in older adults, can be reduced with proper diet and exercise. Trial Registration: ClinicalTrials.gov Identifier: NCT02333331; EudraCT number: 2014-003482-25.

Total body skeletal muscle mass estimated by magnetic resonance imaging and creatine (methyl-d3 ) dilution in athletes.

Creatine dilution (D3 -cr) is a technique for estimating total skeletal muscle mass (SMM) with practical utility, but has not been applied in athletic populations where body composition may differ to that in the normal population. This study aimed to assess the agreement between SMM derived from both D3 -cr and that obtained from whole-body magnetic resonance imaging (MRI) in 15 male and 5 female national level kayakers (stature: 182.0 ± 13.1 and 170.0 ± 9.0 cm; body mass: 80.6 ± 9.9 and 66.4 ± 6.0 kg; V̇O2 peak: 56.5 ± 7.0 and 49.6 ± 4.4 mL kg-1  min-1 , mean ± SD). SMM was determined following 60 mg of dosed D3 -cr and analysis of expelled urine collected on four subsequent days for creatine, creatinine, D3 -cr, and D3 -creatinine using liquid chromatography/mass spectroscopy. SMM was then estimated by assuming a creatine pool size of 4.3 g/kg. During the same time period, a whole-body MRI was undertaken to derive SMM from the analysis of multiple slices taken across the body. A strong positive correlation (F = 74.32; R = 0.90; P < .0001) between the two methods was observed, but the D3 -cr SMM was found to be significantly higher (43.3 ± 6.8 kg) when compared with MRI (36.3 ± 5.8 kg, P < .0001). However, the difference between the methods was removed when a higher intramuscular creatine pool (5.1 g/kg) was assumed. These data show that D3 -cr has potential utility in athletes, as referenced against MRI, but show that assumptions regarding creatine pool size need to be carefully considered.

Emerging Interventions for Elderly Patients-The Promise of Regenerative Medicine.

The impressive increase in lifespan that occurred in the 20th century has driven a boom in age-associated degeneration resulting from senescence. Geriatric syndromes, such as sarcopenia and frailty, do not fall neatly into classical medical definitions of disease because they result from subtle declines in physiological function that occur over many years instead of specific organ-related pathology. These conditions have become more clinically prominent with the aging population and are the focus of research in regenerative medicine. Two major approaches are being pursued: the first targets specific organs that are adversely affected by senescence, and the second targets senescence pathways themselves, with the goal of favorably altering the affected physiology. This review will highlight a few examples of recent applications of both of these approaches to illustrate the potential of the application of a regenerative medicine approach to improve the quality of life and independence in older adults.

Trunk Muscle Composition 2 Months After Hip Fracture: Findings From the Baltimore Hip Studies.

OBJECTIVE: To determine if hip fracture patients would have smaller cross-sectional area (CSA) and lower radiological attenuation (suggesting greater fat infiltration) in all trunk muscles as compared to older adults without hip fractures. DESIGN: Cross-sectional analysis of computed tomography (CT) scans. SETTING: Clinical imaging facility. PARTICIPANTS: Forty-one white participants (19 men, 22 women) from the Baltimore Hip Studies seventh cohort at 2 months postfracture were compared to 693 white participants (424 men, 269 women) from the Health, Aging and Body Composition (Health ABC) study at the year 6 visit (N=734). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Trunk muscle CSA and attenuation values were obtained from a single 10-mm, axial CT scan completed at the L4-L5 disc space in each participant. RESULTS: The hip fracture cohort had significantly smaller CSA for all trunk muscles (range: 12.1%-38% smaller) compared to the Health ABC cohort (P<.01), with the exception of the rectus abdominus muscle in men (P=.12). But, hip fracture patients, particularly female patients, had higher attenuation levels (lower intramuscular fat) in all trunk muscles (P<.0001). CONCLUSIONS: Findings are consistent with atrophy of the trunk muscles in the hip fracture population without a high level of intramuscular fat. Future work should evaluate the role of trunk muscle composition in the functional recovery of older adults after hip fracture.

Creatine ( methyl-d3) dilution in urine for estimation of total body skeletal muscle mass: accuracy and variability vs. MRI and DXA.

A noninvasive method to estimate muscle mass based on creatine ( methyl-d3) (D3-creatine) dilution using fasting morning urine was evaluated for accuracy and variability over a 3- to 4-mo period. Healthy older (67- to 80-yr-old) subjects ( n = 14) with muscle wasting secondary to aging and four patients with chronic disease (58-76 yr old) fasted overnight and then received an oral 30-mg dose of D3-creatine at 8 AM ( day 1). Urine was collected during 4 h of continued fasting and then at consecutive 4- to 8-h intervals through day 5. Assessment was repeated 3-4 mo later in 13 healthy subjects and 1 patient with congestive heart failure. Deuterated and unlabeled creatine and creatinine were measured using liquid chromatography-tandem mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by whole body MRI and 24-h urine creatinine, and lean body mass (LBM) was measured by dual-energy X-ray absorptiometry (DXA). D3-creatinine urinary enrichment from day 5 provided muscle mass estimates that correlated with MRI for all subjects ( r = 0.88, P < 0.0001), with less bias [difference from MRI = -3.00 ± 2.75 (SD) kg] than total LBM assessment by DXA, which overestimated muscle mass vs. MRI (+22.5 ± 3.7 kg). However, intraindividual variability was high with the D3-creatine dilution method, with intrasubject SD for estimated muscle mass of 2.5 kg vs. MRI (0.5 kg) and DXA (0.8 kg). This study supports further clinical validation of the D3-creatine method for estimating muscle mass. NEW & NOTEWORTHY Measurement of creatine ( methyl-d3) (D3-creatine) and D3-creatinine excretion in fasted morning urine samples may be a simple, less costly alternative to MRI or dual-energy X-ray absorptiometry (DXA) to calculate total body muscle mass. The D3-creatine enrichment method provides estimates of muscle mass that correlate well with MRI, and with less bias than DXA. However, intraindividual variability is high with the D3-creatine method. Studies to refine the spot urine sample method for estimation of muscle mass may be warranted.

Measurement of muscle mass in sarcopenia: from imaging to biochemical markers.

Sarcopenia encompasses the loss of muscle mass and strength/function during aging. Several methods are available for the estimation of muscle or lean body mass. Popular assessment tools include body imaging techniques (e.g., magnetic resonance imaging, computed tomography, dual X-ray absorptiometry, ultrasonography), bioelectric impedance analysis, anthropometric parameters (e.g., calf circumference, mid-arm muscle circumference), and biochemical markers (total or partial body potassium, serum and urinary creatinine, deuterated creatine dilution method). The heterogeneity of the populations to be evaluated as well as the setting in which sarcopenia is investigated impacts the definition of "gold standard" assessment techniques. The aim of this article is to critically review available methods for muscle mass estimation, highlighting strengths and weaknesses of each of them as well as their proposed field of application.

Biomarkers for physical frailty and sarcopenia.

Physical frailty (PF) and sarcopenia are major health issues in geriatric populations, given their high prevalence and association with several adverse outcomes. Nevertheless, the lack of an univocal operational definition for the two conditions has so far hampered their clinical implementation. Existing definitional ambiguities of PF and sarcopenia, together with their complex underlying pathophysiology, also account for the absence of robust biomarkers that can be used for screening, diagnostic and/or prognostication purposes. This review provides an overview of currently available biological markers for PF and sarcopenia, as well as a critical appraisal of strengths and weaknesses of traditional procedures for biomarker development in the field. A novel approach for biomarker identification and validation, based on multivariate methodologies, is also discussed. This strategy relies on the multidimensional modeling of complementary biomarkers to cope with the phenotypical and pathophysiological complexity of PF and sarcopenia. Biomarkers identified through the implementation of multivariate strategies may be used to support the detection of the two conditions, track their progression over time or in response to interventions, and reveal the onset of complications (e.g., mobility disability) at a very early stage.

Effects of Prefracture Depressive Illness and Postfracture Depressive Symptoms on Physical Performance After Hip Fracture.

OBJECTIVES: To compare the effect of prefracture depressive illness and postfracture depressive symptoms on changes in physical performance after hip fracture. DESIGN: Longitudinal observational cohort. SETTING: Baltimore metropolitan area. PARTICIPANTS: Older adults with hip fracture (N = 255). MEASUREMENTS: Prefracture depressive illness (from medical records) at baseline and postfracture depressive symptoms at 2 months (using the Center for Epidemiologic Studies Depression Scale) were measured. Physical performance was measured 2, 6, and 12 months after fracture using the Short Physical Performance Battery (SPPB), a composite metric of functional status with a score ranging from 0 to 12. Weighted estimating equations were used to assess mean SPPB over time, comparing participants with and without prefracture depressive illness and subjects with and without postfracture depressive symptoms. RESULTS: Participants with prefracture depressive illness had an SPPB increase of 0.4 units (95% confidence interval (CI) = -0.5-1.3) from 2 to 6 months, smaller than the increase of 1.0 SPPB unit (95% CI = 0.4-1.6) in those without prefracture depressive illness. Participants with postfracture depressive symptoms had an SPPB increase of 0.2 units (95% CI = -1.0-1.5) from 2 to 12 months, and those without postfracture depressive symptoms had a larger increase of 1.2 units (95% CI = 0.6-1.8) over the same period. Nevertheless, prefracture depressive illness and postfracture depressive symptoms were not significantly associated with SPPB. CONCLUSIONS: Neither prefracture depressive illness nor postfracture depressive symptoms were significantly associated with changes in physical performance after hip fracture, but the magnitude of estimates suggested possible clinically meaningful effects on functional recovery.

Biomarkers for physical frailty and sarcopenia: state of the science and future developments.

Physical frailty and sarcopenia are two common and largely overlapping geriatric conditions upstream of the disabling cascade. The lack of a unique operational definition for physical frailty and sarcopenia and the complex underlying pathophysiology make the development of biomarkers for these conditions extremely challenging. Indeed, the current definitional ambiguities of physical frailty and sarcopenia, together with their heterogeneous clinical manifestations, impact the accuracy, specificity, and sensitivity of individual biomarkers proposed so far. In this review, the current state of the art in the development of biomarkers for physical frailty and sarcopenia is presented. A novel approach for biomarker identification and validation is also introduced that moves from the 'one fits all' paradigm to a multivariate methodology.

Asymmetry in CT Scan Measures of Thigh Muscle 2 Months After Hip Fracture: The Baltimore Hip Studies.

BACKGROUND: Hip fracture is an important problem for older adults with significant functional consequences. After hip fracture, reduced muscle loading can result in muscle atrophy. METHODS: We compared thigh muscle characteristics in the fractured leg with those in the nonfractured leg in participants from the Baltimore Hip Studies 7th cohort using computed tomography (CT) scan imaging. RESULTS: At 2 months postfracture, a single 10-mm axial CT scan was obtained at the midthigh level in 47 participants (26 men and 21 women) with a mean age of 80.4 years (range 65-96), and thigh muscle cross-sectional area (CSA), CSA of intermuscular adipose tissue (IMAT), as well as mean radiological attenuation were measured. Total thigh muscle CSA was less on the side of the fracture by 9.2 cm(2) (95% CI: 5.9, 12.4 cm(2)), whereas the CSA of IMAT was greater by 2.8 cm(2) (95% CI: 1.9, 3.8 cm(2)) on the fractured side. Mean muscle attenuation was lower on the side of the fracture by 3.61 HU (95% CI: 2.99, 4.24 HU). CONCLUSIONS: The observed asymmetry is consistent with the effect of disuse and inflammation in the affected limb along with training effects in the unaffected limb due to the favoring of this leg with ambulation during the postfracture period.

Asymmetry in CT Scan Measures of Thigh Muscle 2 Months After Hip Fracture: The Baltimore Hip Studies.

BACKGROUND: Hip fracture is an important problem for older adults with significant functional consequences. After hip fracture, reduced muscle loading can result in muscle atrophy. METHODS: We compared thigh muscle characteristics in the fractured leg to those in the nonfractured leg in participants from the Baltimore Hip Studies 7th cohort using computed tomography scan imaging. RESULTS: At 2 months postfracture, a single 10mm axial computed tomography scan was obtained at the midthigh level in 43 participants (23 men, 20 women) with a mean age of 79.9 years (range: 65-96 years), and thigh muscle cross-sectional area, cross-sectional area of intermuscular adipose tissue, and mean radiologic attenuation were measured. Total thigh muscle cross-sectional area was less on the side of the fracture by 9.46cm(2) (95% CI: 5.97cm(2), 12.95cm(2)) while the cross-sectional area of intermuscular adipose tissue was greater by 2.97cm(2) (95% CI: 1.94cm(2), 4.01cm(2)) on the fractured side. Mean muscle attenuation was lower on the side of the fracture by 3.66 Hounsfield Units (95% CI: 2.98 Hounsfield Units, 4.34 Hounsfield Units). CONCLUSIONS: The observed asymmetry is consistent with the effect of disuse and inflammation in the affected limb along with training effects in the unaffected limb due to the favoring of this leg with ambulation during the postfracture period.

Total body skeletal muscle mass: estimation by creatine (methyl-d3) dilution in humans.

Current methods for clinical estimation of total body skeletal muscle mass have significant limitations. We tested the hypothesis that creatine (methyl-d3) dilution (D3-creatine) measured by enrichment of urine D3-creatinine reveals total body creatine pool size, providing an accurate estimate of total body skeletal muscle mass. Healthy subjects with different muscle masses [n = 35: 20 men (19-30 yr, 70-84 yr), 15 postmenopausal women (51-62 yr, 70-84 yr)] were housed for 5 days. Optimal tracer dose was explored with single oral doses of 30, 60, or 100 mg D3-creatine given on day 1. Serial plasma samples were collected for D3-creatine pharmacokinetics. All urine was collected through day 5. Creatine and creatinine (deuterated and unlabeled) were measured by liquid chromatography mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DXA), and traditional 24-h urine creatinine. D3-creatine was rapidly absorbed and cleared with variable urinary excretion. Isotopic steady-state of D3-creatinine enrichment in the urine was achieved by 30.7 ± 11.2 h. Mean steady-state enrichment in urine provided muscle mass estimates that correlated well with MRI estimates for all subjects (r = 0.868, P < 0.0001), with less bias compared with lean body mass assessment by DXA, which overestimated muscle mass compared with MRI. The dilution of an oral D3-creatine dose determined by urine D3-creatinine enrichment provides an estimate of total body muscle mass strongly correlated with estimates from serial MRI with less bias than total lean body mass assessment by DXA.

Failure of clinical practice guidelines to meet institute of medicine standards: Two more decades of little, if any, progress.

BACKGROUND: In March 2011, the Institute of Medicine (IOM) issued a new set of standards for clinical practice guidelines intended to enhance the quality of guidelines being produced. To our knowledge, no systematic review of adherence to such standards has been undertaken since one published over a decade ago. METHODS: Two reviewers independently screened 130 guidelines selected at random from the National Guideline Clearinghouse (NGC) website for compliance with 18 of 25 IOM standards. RESULTS: The overall median number (percentage) of IOM standards satisfied (out of 18) was 8 (44.4%), with an interquartile range of 6.5 (36.1%) to 9.5 (52.8%). Fewer than half of the guidelines surveyed met more than 50% of the IOM standards. Barely a third of the guidelines produced by subspecialty societies satisfied more than 50% of the IOM standards surveyed. Information on conflicts of interest (COIs) was given in fewer than half of the guidelines surveyed. Of those guidelines including such information, COIs were present in over two-thirds of committee chairpersons (71.4%) and 90.5% of co-chairpersons. Except for US government agency­produced guidelines, criteria used to select committee members and the selection process were rarely described. Committees developing guidelines rarely included an information scientist or a patient or patient representative. Non-English literature, unpublished data, and/or abstracts were rarely considered in developing guidelines; differences of opinion among committee members generally were not aired in guidelines; and benefits of recommendations were enumerated more often than potential harms. Guidelines published from 2006 through 2011 varied little with regard to average number of IOM standards satisfied. CONCLUSION: Analysis of a random sample of clinical practice guidelines archived on the NGC website as of June 2011 demonstrated poor compliance with IOM standards, with little if any improvement over the past 2 decades.

Higher serum concentrations of dietary antioxidants are associated with lower levels of inflammatory biomarkers during the year after hip fracture.

BACKGROUND & AIMS: Chronic inflammation impairs recovery among the 1.6 million people who suffer from hip fracture annually. Vitamin E and the carotenoids are two classes of dietary antioxidants with profound anti-inflammatory effects, and the goal of this study was to assess whether higher post-fracture concentrations of these antioxidants were associated with lower levels of interleukin 6 (IL-6) and the soluble receptor for tumor necrosis factor-alpha (sTNF-αR1), two common markers of inflammation. METHODS: Serum concentrations of the dietary antioxidants and inflammatory markers were assessed at baseline and 2, 6, and 12 month follow-up visits among 148 hip fracture patients from The Baltimore Hip Studies. Generalized estimating equations modeled the relationship between baseline and time-varying antioxidant concentrations and inflammatory markers. RESULTS: Higher post-fracture concentrations of vitamin E and the carotenoids were associated with lower levels of inflammatory markers. Associations were strongest at baseline, particularly between the α-tocopherol form of vitamin E and sTNF-αR1 (p = 0.05) and total carotenoids and both sTNF-αR1(p = 0.01) and IL-6 (p = 0.05). Higher baseline and time-varying α-carotene and time-varying lutein concentrations were also associated with lower sTNF-αR1 at all post-fracture visits (p ≤ 0.05). CONCLUSIONS: These findings suggest that a clinical trial increasing post-fracture intake of vitamin E and the carotenoids may be warranted.

Serum 25-hydroxyvitamin D, transitions between frailty states, and mortality in older adults: the Invecchiare in Chianti Study.

OBJECTIVES: To assess whether serum 25-hydroxyvitamin D (25(OH)D) concentrations relate to transitions between the states of robustness, prefrailty, and frailty and to mortality in older adults. DESIGN: The Invecchiare in Chianti (InCHIANTI) Study, a prospective cohort study. SETTING: Tuscany, Italy. PARTICIPANTS: Adults aged 65 and older (N = 1,155). MEASUREMENTS: Serum 25(OH)D concentrations measured at baseline; frailty state (robust, prefrail, frail) assessed at baseline and 3 and 6 years after enrollment; and vital status determined 3 and 6 years after enrollment. RESULTS: The median (interquartile range) 25(OH)D concentration was 16.0 ng/mL (10.4-25.6 ng/mL; multiply by 2.496 to convert to nmol/L). Prefrail participants with 25(OH)D levels less than 20 ng/mL were 8.9% (95% confidence interval (CI) = 2.5-15.2%) more likely to die, 3.0% (95% CI = -5.6-14.6%) more likely to become frail, and 7.7% (95% CI = -3.5-18.7%) less likely to become robust than prefrail participants with 25(OH)D levels of 20 ng/mL or more. In prefrail participants, each 5-ng/mL decrement of continuous 25(OH)D was associated with 1.46 times higher odds of dying (95% CI = 1.18-2.07) and 1.13 higher odds of incident frailty (95% CI = 0.90-1.39) than with recovery of robustness. Transitions from robustness or frailty were not associated with 25(OH)D levels. CONCLUSION: Results provide evidence that prefrailty is an "at risk" state from which older adults with high 25(OH)D levels are more likely to recover than to decline, but high 25(OH)D levels were not associated with recovery from frailty. Thus, 25(OH)D levels should be investigated as a potential therapy to treat prefrailty and prevent further decline.

Comparing reports from hip-fracture patients and their proxies: implications on evaluating sex differences in disability and depressive symptoms.

OBJECTIVE: This study compared sex differences in disability and depressive symptoms using reports from hip fracture patients and their proxies. METHOD: Hip fracture patients (49 men, 183 women) aged ≥65 years and proxies were interviewed 1 year postfracture. Outcomes were Center for Epidemiological Studies Depression (CES-D) and number of dependencies in performing activities of daily living and instrumental activities of daily living. RESULTS: Mean ADL sex differences (men minus women) were 0.40 (p = .37) using proxy reports and 0.70 (p = .08) using patient self-reports. Mean CES-D sex differences were -3.60 (p = .02) using proxy reports and -1.26 (p = .38) using patient self-reports. Discrepancies between patients and proxies were smallest for proxies who have lived with the patient ≥ 1 year. DISCUSSION: Patients and proxies produced conflicting conclusions about sex differences. Results suggest that ideal proxies to recruit are those who have been cohabitating with the patients for an extended length of time.

Absolute strength and loss of strength as predictors of mobility decline in older adults: the InCHIANTI study.

BACKGROUND: Theoretical definitions of sarcopenia traditionally emphasize age-related loss of muscle strength; however, most analyses of the association between strength and mobility examine strength at a single time point. This study sought to identify sex-specific cutpoints for muscle strength and power (at one time point) and 3-year changes in strength and power that would maximize prediction of 3-year mobility decline. METHODS: Longitudinal analysis of 934 adults aged ≥65 years enrolled in the Invecchiare in Chianti study was conducted. Grip strength, knee extension strength, and lower extremity power were measured at baseline and 3 years postenrollment. Mobility function (gait speed and self-reported mobility disability) was measured at 3 and 6 years postenrollment. Classification and regression tree analysis was used to predict mobility decline from Years 3 to 6. RESULTS: Men with knee extension strength <19.2 kg and grip strength <39.0 kg had clinically meaningful declines in gait speed of .24 m/s. Furthermore, men with power <105 W were nearly nine times more likely to develop incident mobility disability (likelihood ratio = 8.68; 95% confidence interval = 3.91, 19.44). Among women, knee extension strength <18.0 kg was associated with a minimal gait speed decline of 0.06 m/s, and women with leg power <64 W were three times more likely to develop incident mobility disability (likelihood ratio = 3.01; 95% confidence interval = 1.79, 5.08). Three-year changes in strength and power did not predict mobility decline in either sex. CONCLUSIONS: Findings suggest that strength and power measured at one time point are more predictive of mobility decline than 3-year changes and that low strength and power are particularly powerful risk factors in men.