Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.

The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan1-3. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients4, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm)5-7, and is established to increase healthy lifespan in multiple species8,9. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n = 220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2 yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health11-13. The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14-16 and contrasting with reports that biological aging may not be modifiable17. Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality18-20.

Zoledronic acid reduces the rate of clinical fractures after surgical repair of a hip fracture regardless of the Pretreatment bone mineral density.

In patients with surgical repair of a low-trauma hip fracture, zoledronic acid (ZA) reduced the risk of subsequent fractures regardless of pretreatment femoral neck and total hip bone mineral density (BMD). INTRODUCTION: Zoledronic acid reduces the risk of subsequent fractures after repair of a hip fracture. It is still unclear whether the benefits in fracture reduction with ZA depend upon hip bone mineral density at the time of fracture. METHODS: We preformed additional post hoc analyses of data from the HORIZON Recurrent Fracture Trial to determine if ZA treatment reduced the risk of new clinical fractures regardless of pretreatment BMD. We modeled femoral neck and total hip BMD as both continuous and dichotomous variables (BMD T-score above and below -2.5). RESULTS: There are no evidence that baseline femoral neck and total hip BMD modified the anti-fracture efficacy of ZA when pretreatment BMD was analyzed as a continuous or a dichotomous variable (interaction p-values > 0.20). The clinical fracture efficacy of ZA was similar among patients with pretreatment femoral neck BMD values above and below -2.5 (relative hazards = 0.60 and 0.67, respectively, interaction p-value = 0.95). A similar result was obtained using pretreatment total hip BMD values (relative hazards = 0.72 and 0.57, respectively, interaction p-value = 0.41). CONCLUSION: There data should provide more comfort in prescribing ZA after surgical repair of a hip fracture, regardless of pretreatment BMD.

Quality of Life and Mental Health in Older Adults with Obesity and Frailty: Associations with a Weight Loss Intervention.

OBJECTIVE: To examine the bi-directional associations of a weight loss intervention with quality of life and mental health in obese older adults with functional limitations. DESIGN: Combined-group analyses of secondary variables from the MEASUR-UP randomized controlled trial. SETTING: Academic medical center. PARTICIPANTS: Obese community-dwelling men and women (N = 67; age ≥60; BMI ≥30) with functional limitations (Short Physical Performance Battery [SPPB] score of 4-10 out of 12). INTERVENTION: Six-month reduced calorie diet at two protein levels. MEASUREMENTS: Weight, height, body composition, physical function, medical history, and mental health and quality of life assessments (Center for Epidemiologic Studies Depression Scale [CES-D]; Profile of Mood States [POMS], Pittsburgh Sleep Quality Index [PSQI]; Perceived Stress Scale [PSS]; Satisfaction with Life Scale [SWLS]; and Short Form Health Survey [SF-36]) were acquired at 0, 3 and 6 months. RESULTS: Physical composite quality of life (SF-36) improved significantly at 3 months (ß = 6.29, t2,48 = 2.60, p = 0.012) and 6 months (ß = 10.03, t2,48 = 4.83, p < 0.001), as did several domains of physical quality of life. Baseline depression symptoms (CES-D and POMS) were found to predict lower amounts of weight loss; higher baseline sleep latency (PSQI) and anger (POMS) predicted less improvement in physical function (SPPB). CONCLUSION: The significant bi-directional associations found between a weight loss intervention and mental health/quality of life, including substantial improvements in physical quality of life with obesity treatment, indicate the importance of considering mental health and quality of life as part of any weight loss intervention for older adults.

Anxiety symptoms bias memory assessment in older adults.

BACKGROUND: Older adults with anxiety and/or depression experience additional memory dysfunction beyond that of the normal aging process. However, few studies have examined test bias in memory assessments due to anxiety and/or depressive symptoms. The current study investigated the influence of self-reported symptoms of anxiety and depression on the measurement equivalence of memory tests in older adults. METHOD: This is a secondary analysis of the Advanced Cognitive Training for Independent and Vital Elderly dataset, a randomized controlled trial of community-dwelling older adults. Baseline data were included in this study (n = 2802). Multiple indicators multiple causes modeling was employed to assess for measurement equivalence, differential item functioning (DIF), in memory tests. RESULTS: The DIF was present for anxiety symptoms but not for depressive symptoms, such that higher anxiety placed older adults at a disadvantage on measures of memory performance. Analysis of DIF impact showed that compared with participants scoring in the bottom quartile of anxious symptoms, participants in the upper quartile exhibited memory performance scores that were 0.26 standard deviation lower. CONCLUSION: Anxious but not depressive symptoms introduce test bias into the measurement of memory in older adults. This indicates that memory models for research and clinical purposes should account for the direct relationship between anxiety symptoms and memory tests in addition to the true relationship between anxiety symptoms and memory construct. These findings support routine assessments of anxiety symptoms among older adults in settings in which cognitive testing is being conducted. Copyright © 2016 John Wiley & Sons, Ltd.

Direct in vivo evidence of activated macrophages in human osteoarthritis.

OBJECTIVE: Through binding to folate receptor-ß (FR-ß), the new (99m)Tc-EC20 (Etarfolatide) imaging technique detects activated but not resting macrophages in vivo. The goal of this study was to investigate macrophage-related inflammation in osteoarthritis (OA). METHODS: Twenty-five individuals (50 knees) with symptomatic OA of at least one knee underwent SPECT-CT imaging of both knees and planar imaging of the whole body after injection of Etarfolatide. Scans and knee radiographs were scored blinded to clinical information including knee and other joint site pain severity. Measures of association controlled for age, gender, body mass index (BMI) and employed repeated measures to adjust for correlation between knees. DESIGN: Activated macrophages were present in the majority (76%) of knees. The quantity of knee-related macrophages was significantly associated with knee pain severity (R = 0.60, P < 0.0001) and radiographic knee OA severity including joint space narrowing (R = 0.68, P = 0.007), and osteophyte (R = 0.66, P = 0.001). Macrophages were also localized to joints commonly affected by OA including hand finger joints (12%), thumb bases (28%), shoulders (26%), great toes (18%) and ankles (12%). The presence of joint pain at fingers, wrists, ankles and great toes was significantly positively associated with presence of activated macrophages at these sites (P < 0.0001-0.04). CONCLUSIONS: This study provides the first direct in vivo evidence for macrophage involvement in OA in a substantial proportion of human knees. The association of quantity of activated macrophages with radiographic knee OA severity and joint symptoms suggests that drugs targeting macrophages and macrophage-associated inflammatory pathways may have the potential to be both symptom and structure modifying.

Self-efficacy for exercise, more than disease-related factors, is associated with objectively assessed exercise time and sedentary behaviour in rheumatoid arthritis.

OBJECTIVES: Until recently, reports of physical activity in rheumatoid arthritis (RA) were limited to self-report methods and/or leisure-time physical activity. Our objectives were to assess, determine correlates of, and compare to well-matched controls both exercise and sedentary time in a typical clinical cohort of RA. METHOD: Persons with established RA (seropositive or radiographic erosions; n = 41) without diabetes or cardiovascular disease underwent assessments of traditional and disease-specific correlates of physical activity and 7 days of triaxial accelerometry. Twenty-seven age, gender, and body mass index (BMI)-matched controls were assessed. RESULTS: For persons with RA, objectively measured median (25th-75th percentile) exercise time was 3 (1-11) min/day; only 10% (n = 4) of participants exercised for ≥ 30 min/day. Time spent in sedentary activities was 92% (89-95%). Exercise time was not related to pain but was inversely related to disease activity (r = -0.3, p < 0.05) and disability (r = -0.3, p < 0.05) and positively related to self-efficacy for endurance activity (r = 0.4, p < 0.05). Sedentary activity was related only to self-efficacy for endurance activity (r = -0.4, p < 0.05). When compared to matched controls, persons with RA exhibited poorer self-efficacy for physical activity but similar amounts of exercise and sedentary time. CONCLUSIONS: For persons with RA and without diabetes or cardiovascular disease, time spent in exercise was well below established guidelines and activity patterns were predominantly sedentary. For optimal care in RA, in addition to promoting exercise, clinicians should consider assessing sedentary behaviour and self-efficacy for exercise. Future interventions might determine whether increased self-efficacy can increase physical activity in RA.

High prevalence of contralateral ankle abnormalities in association with knee osteoarthritis and malalignment.

OBJECTIVE: To evaluate ankle joint abnormalities in a knee osteoarthritis (OA) cohort. METHODS: Participants (n = 159) with symptomatic and radiographic OA in at least one knee underwent technetium-99m methylene diphosphonate bone scan (scored 0-3) of the ankles and forefeet. Knee radiographs were graded for OA features of joint space narrowing (JSN) and osteophyte (OST). Ankle symptoms and history of ankle injury were assessed by self-report. Knee alignment was measured from a long-limb radiograph. Ankle radiographs were obtained on those who returned for follow-up (n = 138) and were graded for ankle tibiotalar JSN and OST. DESIGN: Ankle scintigraphic abnormalities were frequent (31% of individuals, one-third bilateral). Ankle symptoms were reported by 23% of individuals and history of ankle injury by 24%. Controlling for gender, age, body mass index (BMI), and contralateral predictor, ankle scintigraphic abnormalities were associated with: ipsilateral ankle symptoms (P = 0.005); contralateral knee JSN (P = 0.001), knee OST (P = 0.006) and knee malalignment (P = 0.08); and history of ankle injury or surgery of either ankle (P < 0.0001). At follow-up, scintigraphic abnormalities of the ankle were strongly associated with presence of tibiotalar radiographic OA (P < 0.0001). CONCLUSIONS: Although considered rare, we observed a high prevalence of radiographic features of ankle OA in this knee OA cohort. History of overt ankle injury did not appear to account for the majority of ankle abnormalities. These results are consistent with a probable kinematic association of knee OA pathology and contralateral ankle abnormalities and suggest that interventions targeting mechanical factors may be needed to prevent ankle OA in the setting of knee OA.

Zoledronic acid results in better health-related quality of life following hip fracture: the HORIZON-Recurrent Fracture Trial.

UNLABELLED: This study evaluated the benefits of ZOL versus placebo on health-related quality of life (HRQoL) among patients from HORIZON-RFT. At month 24 and end of the study visit, ZOL significantly improved patients' overall health state compared to placebo as assessed by the EQ-5D VAS. INTRODUCTION: To evaluate the benefits of zoledronic acid (ZOL) versus placebo on health-related quality of life (HRQoL) among patients from The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Recurrent Fracture Trial (HORIZON-RFT). METHODS: In this randomized, double-blind, placebo-controlled trial, 2,127 patients were randomized to receive annual infusion of ZOL 5 mg (n = 1,065) or placebo (n = 1,062) within 90 days after surgical repair of low-trauma hip fracture. HRQoL was measured using EQ-5D Visual Analogue Scale (VAS) and utility scores (EuroQol instrument) at months 6, 12, 24, 36, and end of the study visit. Analysis of covariance model included baseline EQ-5D value, region, and treatment as explanatory variables. RESULTS: At baseline, patients (mean age 75 years; 24% men and 76% women) were well matched between treatment groups with mean EQ-5D VAS of 65.82 in ZOL and 65.70 in placebo group. At the end of the study, mean change from baseline in EQ-5D VAS was greater for ZOL vs. placebo in all patients (7.67 ± 0.56 vs. 5.42 ± 0.56), and in subgroups of patients experiencing clinical vertebral fractures (8.86 ± 4.91 vs. -1.69 ± 3.42), non-vertebral fractures (5.03 ± 2.48 vs. -1.07 ± 2.16), and clinical fractures (5.19 ± 2.25 vs. -0.72 ± 1.82) with treatment difference significantly in favor of ZOL. EQ-5D utility scores were comparable for ZOL and placebo groups, but more patients on placebo consistently had extreme difficulty in mobility (1.74% for ZOL vs. 2.13% for placebo; p = 0.6238), self-care (4.92% vs. 6.69%; p = 0.1013), and usual activities (10.28% vs. 12.91%; p = 0.0775). CONCLUSION: ZOL significantly improves HRQoL in patients with low-trauma hip fracture.

Is diabetes associated with poorer self-efficacy and motivation for physical activity in older adults with arthritis?

OBJECTIVES: The primary aim was to explore whether arthritis is associated with poorer self-efficacy and motivation for, and participation in, two specific types of physical activity (PA): endurance training (ET) and strength training (ST). A further objective was to determine whether the added burden of diabetes contributes to a further reduction in these PA determinants and types. METHODS: Self-efficacy and motivation for exercise and minutes per week of ET and ST were measured in 347 older veterans enrolled in a home-based PA counselling intervention. Regression analyses were used to compare high versus low self-efficacy and motivation and PA minutes in persons without arthritis, with arthritis alone, and with arthritis plus diabetes. RESULTS: Persons with arthritis alone reported lower self-efficacy for ET and ST than those without arthritis [odds ratio (OR)ET 0.71, 95% confidence interval (CI) 0.39­1.20; ORST 0.69, 95% CI 0.39­1.20]. A further reduction in self-efficacy for these two types of PA was observed for those with both arthritis and diabetes (ORET 0.65, 95% CI 0.44­0.92; ORST 0.64, 95% CI 0.44­0.93; trend p < 0.001). There was no trend towards a reduction in motivation for PA in those with arthritis alone or with arthritis and diabetes. Persons with arthritis exhibited higher motivation for ET than those without arthritis (ORET 1.85, 95% CI 1.12­3.33). There were no significant differences between the three groups in minutes of ET (p = 0.93), but persons with arthritis plus diabetes reported significantly less ST compared to individuals with arthritis only (p = 0.03). CONCLUSIONS: Despite reduced self-efficacy for ET and ST and less ST in older persons with arthritis, motivation for both PA types remains high, even in the presence of diabetes.

The impact of self-reported arthritis and diabetes on response to a home-based physical activity counselling intervention.

OBJECTIVES: Physical activity (PA) has the potential to improve outcomes in both arthritis and diabetes, but these conditions are rarely examined together. Our objective was to explore whether persons with arthritis alone or those with both arthritis and diabetes could improve amounts of PA with a home-based counselling intervention. METHODS: As part of the Veterans LIFE (Learning to Improve Fitness and Function in Elders) Study, veterans aged 70-92 were randomized to usual care or a 12-month PA counselling programme. Arthritis and diabetes were assessed by self-report. Mixed models were used to compare trajectories for minutes of endurance and strength training PA for persons with no arthritis (n = 85), arthritis (n = 178), and arthritis plus diabetes (n = 84). RESULTS: Recipients of PA counselling increased minutes of PA per week independent of disease status (treatment arm by time interaction p < 0.05 for both; endurance training time p = 0.0006 and strength training time p < 0.0001). Although PA was lower at each wave among persons with arthritis, and even more so among persons with arthritis plus diabetes, the presence of these conditions did not significantly influence response to the intervention (arthritis/diabetes group x time interactions p > 0.05 for both outcomes) as each group experienced a nearly twofold or greater increase in PA. CONCLUSIONS: A home-based PA intervention was effective in increasing minutes of weekly moderate intensity endurance and strength training PA in older veterans, even among those with arthritis or arthritis plus diabetes. This programme may serve as a useful model to improve outcomes in older persons with these pervasive diseases.

The complex relationship between depressive symptoms and functional limitations in community-dwelling older adults: the impact of subthreshold depression.

BACKGROUND: Depressive symptoms above screening thresholds have been shown to predict functional decline in older adults. Less is known about the impact of subthreshold depression, and whether more symptoms confer significantly greater risk compared to fewer symptoms. METHOD: Using data from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE) collected over 10 years, we used repeated-measures mixed models to predict functional change by depression status at the prior (index) in-person interview. Depressive symptoms were measured using a modified version of the Center for Epidemiologic Studies Depression Scale (CES-D). Subthreshold depression was operationalized as 6-8 symptoms and CES-D-defined depression as 9-20 symptoms in the previous week. Three domains of functional status were assessed at the subsequent in-person interview: limitations in basic activities of daily living (ADL), instrumental ADL (IADL) and mobility. RESULTS: Controlling for race, sex, age, education, marital status, cognitive status, health status, self-perceived health, perceived social support and functional status at the index interview, having 6 depressive symptoms predicted an increase of 0.12 IADL limitations 3-4 years later (p=0.03). The incremental effect of CES-D-defined depression (9 symptoms compared to 6-8 symptoms) was not significant, suggesting that the effect of more symptomatic depression did not add to that of subthreshold depression. CES-D score modeled as a continuous variable predicted functional change for all domains, but the relationship was not linear, supporting a possible threshold effect. CONCLUSIONS: The relationship between depressive symptoms and functional change is complex, not necessarily linear, and may vary by tasks assessed.

Common causes of open-circuit recreational diving fatalities.

Diving fatalities causes were investigated in 947 recreational open-circuit scuba diving deaths from 1992-2003. Where possible, cases were classified at each step of a four step sequence: trigger, disabling agent, disabling injury, cause of death (COD). The most frequent adverse events within each step were: (a) triggers 41% insufficient gas, 20% entrapment, 15% equipment problems; (b) disabling agents--55% emergency ascent, 27% insufficient gas, 13% buoyancy trouble; (c) disabling injuries--33% asphyxia, 29% arterial gas embolism (AGE), 26% cardiac incidents; and (d) COD--70% drowning, 14% AGE, 13% cardiac incidents. We concluded that disabling injuries were more relevant than COD as drowning was often secondary to a disabling injury. Frequencies and/ or associations with risk factors were investigated for each disabling injury by logistic regression. (The reference group for each injury was all other injuries.) Frequencies and/or associations included: (a) asphyxia--40% entrapment (Odds Ratio, OR > or = 30), 32% insufficient gas (OR = 15.9), 17% buoyancy trouble, 15% equipment trouble (OR = 4.5), 11% rough water, drysuit (OR = 4.1), female gender (OR = 2.1); (b) AGE--96% emergency ascent (OR > or = 30), 63% insufficient gas, 17% equipment trouble, 9% entrapment; (c) cardiac incidents--cardiovascular disease (OR = 10.5), age > 40 (OR = 5.9). Minimizing the frequent adverse events would have the greatest impact on reducing diving deaths.

Influence of bottom time on preflight surface intervals before flying after diving.

Previous trials of flying at 8,000 ft after a single 60 fsw, 55 min no-stop air dive found low decompression sickness (DCS) risk for a 11:00 preflight surface interval (PFSI). Repetitive 60 fsw no-stop dives with 75 and 95 min total bottom times found 16:00. Trials reported here investigated PFSIs for a 60 fsw, 40 min no-stop dive and a 60 fsw, 120 min decompression dive. The 40 min trials began with a 12:05 PFSI (USN guideline) which was incrementally reduced to 0:05 (three DCS incidents in 281 trials). The 120 min trials began with a 22:46 PFSI (USN guideline) which was reduced to 2:00 (nine incidents in 281 trials); 2:00 was rejected with six incidents. Low-risk PFSIs for the 40 min dive were nearly 12 hours shorter than for the 55 min dive, and low-risk PFSIs for the single 120 min decompression dive were 12 hours shorter than for the 75-95 min repetitive dives. With the dry, resting conditions of these dives, low-risk PFSIs appeared to be sensitive to dive profile characteristics such as bottom time, repetitive diving, and decompression stops. Whether this is so for wet, working dives is unknown.

Does NSAID use modify cognitive trajectories in the elderly? The Cache County study.

BACKGROUND: Epidemiologic studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be useful for the prevention of Alzheimer disease (AD). By contrast, clinical trials have not supported NSAID use to delay or treat AD. Few studies have evaluated cognitive trajectories of NSAID users over time. METHODS: Residents of Cache County, UT, aged 65 or older on January 1, 1995, were invited to participate in the study. At baseline, participants provided a detailed inventory of their medications and completed a revised Modified Mini-Mental State Examination (3MS). Participants (n = 3,383) who were cognitively normal at baseline were re-examined after 3 and 8 years. The association between NSAID use and 3MS scores over time was estimated using random effects modeling. RESULTS: Associations depended upon when NSAIDs were started and APOE genotype. In participants who started NSAID use prior to age 65, those with no APOE epsilon4 alleles performed similarly to nonusers (a difference of 0.10 points per year; p = 0.19), while those with one or more epsilon4 allele(s) showed more protection (0.40 points per year; p = 0.0005). Among participants who first used NSAIDs at or after age 65, those with one or more epsilon4 alleles had higher baseline scores (0.95 points; p = 0.03) but did not show subsequent difference in change in score over time (0.06 points per year; p = 0.56). Those without an epsilon4 allele who started NSAID use after age 65 showed greater decline than nonusers (-0.16 points per year; p = 0.02). CONCLUSIONS: Nonsteroidal anti-inflammatory drug use may help to prevent cognitive decline in older adults if started in midlife rather than late life. This effect may be more notable in those who have one or more APOE epsilon4 alleles.

Identification of VaD and AD prodromes: the Cache County Study.

BACKGROUND: It is unclear whether vascular dementia (VaD) has a cognitive prodrome, akin to the mild cognitive impairment (MCI) prodrome to Alzheimer's dementia (AD). To evaluate whether VaD has a cognitive prodrome, and if it can be differentiated from prodromal AD, we examined neuropsychological test performance of participants in a nested case-control study within a population-based cohort aged 65 or older. METHODS: Participants (n = 485) were identified from the Cache County Study, a large population-based study of aging and dementia. After an average of 3 years of follow-up, a total of 62 incident dementia cases were identified (14 VaD, 48 AD). We identified a number of neuropsychological tests (executive and memory) that discriminated between diagnosed VaD and AD cases. Multivariate analyses sought to differentiate between these same groups 3 years before clinical diagnosis. RESULTS: The Consortium to Establish a Registry for Alzheimer's Disease Word List Recognition Test correct recognition of foils (mean difference, 1.25; 95% confidence interval [CI], 0.42 to 2.07; p < 0.01), Logical Memory I (mean difference, 7.16; 95% CI, 0.78 to 13.55, p < 0.05), Logical Memory II delayed recall (mean difference, 8.67; 95% CI, 1.59 to 15.74, p < 0.05), and percent savings (mean difference, 51.07; 95% CI, 32.58 to 69.56, p < 0.0001) differentiated VaD from AD cases after adjustment for age, sex, education, and dementia severity. Three years before dementia diagnosis, word list recognition ("no" responses mean difference, 1.40; 95% CI, 0.64 to 2.17; p < 0.001, and "yes" responses mean difference, -1.14; 95% CI, -2.14 to -0.13; p < 0.03) discriminated between prodromal VaD and AD. CONCLUSION: These results suggest that VaD has a prodromal syndrome, the cognitive features of which are distinguishable from the cognitive prodrome of AD.

Assessment of hand osteoarthritis: correlation between thermographic and radiographic methods.

OBJECTIVE: Anatomical stages of digital osteoarthritis (OA) have been characterized radiographically as progressing through sequential phases from normal to osteophyte formation, progressive loss of joint space, joint erosion and joint remodelling. Our study was designed to evaluate a physiological parameter, joint surface temperature, measured with computerized digital infrared thermal imaging, and its association with sequential stages of radiographic OA (rOA). METHODS: Thermograms, radiographs and digital photographs were taken of both hands of 91 subjects with nodal hand OA. Temperature measurements were made on digits 2-5 at distal interphalangeal (DIP) joints, proximal interphalangeal (PIP) joints and metacarpophalangeal (MCP) joints (2184 joints in total). We fitted a repeated measures ANCOVA model to analyse the effects of rOA on temperature, with handedness, joint group, digit and NSAID use as covariates. RESULTS: The reliability of the thermoscanning procedure was high (generalizability coefficient 0.899 for two scans performed 3 h apart). The mean joint temperature decreased with increasing rOA severity, defined by the Kellgren-Lawrence (KL) scale. The mean temperature of KL0 joints was significantly different from that of each of the other KL grades (P

Experimental trials to assess the risks of decompression sickness in flying after diving.

We conducted experimental trials of flying after diving using profiles near the no-decompression exposure limits for recreational diving. The objective was to determine the dependence of DCS occurrence during or after flight on the length of the preflight surface intervals (PFSI). One to three dives were conducted during a single day with dry, resting subjects in a hyperbaric chamber at depths of 40, 60, or 100 fsw (224, 286, 408 kPa). The dives were followed by PFSI of 3 to 17 hrs and a four-hour altitude exposure at 8,000 ft (75 kPa), the maximum permitted cabin altitude for pressurized commercial aircraft. Forty DCS incidents occurred during or after flight in 802 exposures of 495 subjects. The DCS incidence decreased as PFSI increased, and repetitive dives generally required longer PFSI to achieve low incidence than did single dives (p = 0.0159). No DCS occurred in 52 trials of a 17 hr PFSI, the longest PFSI tested. The results provide empirical information for formulating guidelines for flying in commercial aircraft after recreational diving.

Can historical and functional risk factors be used to predict fractures in community-dwelling older adults? development and validation of a clinical tool.

The objectives of the study were: (1) to evaluate the contribution of impaired functional status, cognition and medication to fracture risk; (2) to determine whether risk factor profiles differ between regionally and socially diverse populations; and (3) to develop and validate a simple fracture prediction instrument for use in older adults using easily obtainable clinical information. A prospective population-based cohort study with 6-10 years of follow-up was carried out: the Duke and Iowa Established Populations for the Epidemiologic Study of the Elderly (EPESE), with in-person interviews in North Carolina and Iowa. The participants were community-dwelling men and women aged 65 years or over without a history of previous fracture at the baseline interview ( n = 7654). The measurements were potential risk factors for osteoporosis and falls including: demographic factors, co-morbidities, medications, functional status measures, and physical measures. These were examined for association with self-reported subsequent hip fractures and fractures at any site using survival analysis. The resulting multivariable model was simplified and validated in a separate cohort. Test operating characteristics at 3 years were estimated using logistic regression. There were a total of 842 fractures in both cohorts including 382 hip fractures. Significant risk factors for all subsequent fractures and/or hip fracture in the developmental cohort included female sex (relative hazard 1.9-2.3), lowest quartile of body mass index (1.3), Caucasian race (2.1-2.8), one or more Rosow-Breslau physical function impairments (1.8-2.1), age over 75 years (2.1), history of stroke (1.9), cognitive impairment (2.2), one or more impairments in the activities of daily living (1.5) and anti-seizure medication use (2.0). Three predicitive models were highly significantly correlated with subsequent fractures with c-statistics in the developmental cohort at 3 and 6 years of 0.640-0.789. A simple count of risk factors had similar discriminative ability to the full model with a linear 35-65% increase in hazard of all fractures and hip fracture for each additional risk factor. In the validation cohort, the above variables were less potent predictors of fracture with only sex, body mass index and Rosow-Breslau impairment achieving significance. The predictive models including risk factor count remained significant in the validation set although the discriminative ability of the model was poor, with c-statistics of 0.574-0.749. Although there is no cut-point where fracture risk dramatically increases, patients can be counselled that there is a linear 77% increase in risk of hip fracture, and 29% increase in any fracture risk, with each additional risk factor they possess. Functional status impairment is an important predictor of fracture in older community-dwelling adults. The contribution of risk factors to fracture risk may differ between distinct populations.