Hospitalization-Associated Change in Gait Speed and Risk of Functional Limitations for Older Adults

BACKGROUND: Hospitalization-associated functional decline is a common problem for older adults, but it is unclear how hospitalizations affect physical performance measures such as gait speed. We sought to determine hospitalization-associated change in gait speed and likelihood of new limitations in mobility and activities of daily living (ADLs). METHODS: We used longitudinal data over 5 years from the Health, Aging and Body Composition Study, a prospective cohort of black and white community-dwelling men and women, aged 70-79 years, who had no limitations in mobility (difficulty walking 1/4 mile or climbing 10 steps) or ADLs (transferring, bathing, dressing, and eating) at baseline. Gait speed, and new self-reported limitations in mobility and ADLs were assessed annually. Selected participants (n = 2,963) had no limitations at the beginning of each 1-year interval. Hospitalizations were self-reported every 6 months and verified with medical record data. Generalized estimating equations were used to examine hospitalization-associated change in gait speed and odds of new limitations over each 1-year interval. Fully adjusted models included demographics, hospitalization within the past year, health conditions, symptoms, body mass index, and health-related behaviors. RESULTS: In fully adjusted models, any hospitalization was associated with decrease in gait speed (-0.04 m/s; 95% confidence interval [CI]: -0.05 to -0.03) and higher odds of new limitations in mobility or ADLs (odds ratio = 1.97, 95% CI: 1.70-2.28), and separately with increased odds of new mobility limitation (odds ratio = 2.22, 95% CI: 1.90-2.60) and new ADL limitations (odds ratio = 1.84, 95% CI: 1.53-2.21). Multiple hospitalizations within a year were associated with gait speed decline (-0.06 m/s; 95% CI: -0.08 to -0.04) and greater odds of new limitations in mobility or ADLs (odds ratio = 2.96, 95% CI: 2.23-3.95). CONCLUSIONS: Functionally independent older adults experienced hospitalization-associated declines in gait speed and new limitations in mobility and ADLs

A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM].

BACKGROUND: MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated. METHODS: To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included. RESULTS: We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpGs 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpGs 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpGs 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions. CONCLUSION: The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted

Anticorps naturels: etude de leur specificite et de leur roele dans la regulation du systeme immunitaire

CNRS AR 11683 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Height Loss in Old Age and Fracture Risk Among Men in Late Life: A Prospective Cohort Study.

To assess the association of height loss in old age with subsequent risk of hip and any clinical fracture in men late in life while accounting for the competing risk of mortality, we used data from 3491 community-dwelling men (mean age 79.2 years). Height loss between baseline and follow-up (mean 7.0 years between examinations) was categorized as <1 cm (referent group), ≥1 to <2 cm, ≥2 to <3 cm, and ≥3 cm. Men were contacted every 4 months after the follow-up examination to ask about fractures (confirmed by radiographic reports) and ascertain vital status (deaths verified by death certificates). Competing risk methods were used to estimate absolute probabilities of fracture outcomes by height loss category and calculate adjusted risks of fracture outcomes by height loss. During an average of 7.8 years, 158 (4.5%) men experienced a hip fracture and 1414 (40.5%) died before experiencing this event. The absolute 10-year probability of fracture events accounting for the competing risk of death increased with greater height loss. For example, the hip fracture probability was 2.7% (95% confidence interval [CI] 1.9-3.8%) among men with height loss <1 cm increasing to 11.6% (95% CI 8.0-16.0%) among men with height loss ≥3 cm. After adjustment for demographics, fall history, multimorbidity, baseline height, weight change, and femoral neck bone mineral density and considering competing mortality risk, men with height loss ≥3 cm versus <1 cm had a nearly twofold (subdistribution hazard ratio [HR] = 1.94, 95% CI 1.06-3.55) higher risk of hip fracture and a 1.4-fold (subdistribution HR = 1.42, 95% CI 1.05-1.91) increased risk of any clinical fracture. Height loss ≥3 cm in men during old age was associated with higher subsequent risk of clinical fractures, especially hip fractures, even after accounting for the competing risk of death and traditional skeletal and non-skeletal risk factors. © 2021 American Society for Bone and Mineral Research (ASBMR)

The Association Between Trabecular Bone Score and Lumbar Spine Volumetric BMD Is Attenuated Among Older Men With High Body Mass Index.

Trabecular bone score (TBS) has been proposed as a dual-energy X-ray absorptiometry (DXA) derived measure of underlying quality of trabecular bone; however, TBS is not considered valid for those with body mass index (BMI) >37 kg/m2 . Our objective was to determine the association between TBS and lumbar spine (trabecular) volumetric BMD (LS-VBMD) and to examine whether the association varied by BMI and body composition among older men below this clinical threshold. We used regression models to study 3479 men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study who had TBS from spine DXA scans, LS-VBMD from central quantitative computed tomography, measures of trunk fat and lean mass from DXA, and BMI <37 kg/m2 . TBS was categorized as normal (n = 925), partially degraded (n = 1747), and degraded (n = 807). TBS was inversely related to BMI, trunk fat mass, and trunk lean mass (all p < 0.001). The relationship between TBS and LS-VBMD was nonlinear with magnitude of effect (slope of regression line using standardized variables) ranging from 0.07 (95% CI, -0.02 to 0.15) among those with degraded TBS up to 0.71 (95% CI, 0.54 to 0.89) among those with normal TBS. The relationship was still nonlinear after adjusting for age, clinical site, and either BMI, trunk lean mass, or trunk fat mass. The magnitude of effect relating TBS and LS-VBMD also decreased with increasing BMI (interaction, p = 0.090) and increasing trunk lean mass (interaction, p = 0.001), but not with increasing trunk fat mass (interaction, p = 0.224). In summary, the strength of the association between TBS and LS-VBMD among older men was variable and dependent on BMI and body composition, particularly trunk lean mass. The clinical utility of TBS among older men may be somewhat limited among men with high BMI or high trunk lean mass. © 2016 American Society for Bone and Mineral Research

The Association Between Trabecular Bone Score and Lumbar Spine Volumetric BMD Is Attenuated Among Older Men With High Body Mass Index.

Trabecular bone score (TBS) has been proposed as a dual-energy X-ray absorptiometry (DXA) derived measure of underlying quality of trabecular bone; however, TBS is not considered valid for those with body mass index (BMI) >37 kg/m2 . Our objective was to determine the association between TBS and lumbar spine (trabecular) volumetric BMD (LS-VBMD) and to examine whether the association varied by BMI and body composition among older men below this clinical threshold. We used regression models to study 3479 men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study who had TBS from spine DXA scans, LS-VBMD from central quantitative computed tomography, measures of trunk fat and lean mass from DXA, and BMI <37 kg/m2 . TBS was categorized as normal (n = 925), partially degraded (n = 1747), and degraded (n = 807). TBS was inversely related to BMI, trunk fat mass, and trunk lean mass (all p < 0.001). The relationship between TBS and LS-VBMD was nonlinear with magnitude of effect (slope of regression line using standardized variables) ranging from 0.07 (95% CI, -0.02 to 0.15) among those with degraded TBS up to 0.71 (95% CI, 0.54 to 0.89) among those with normal TBS. The relationship was still nonlinear after adjusting for age, clinical site, and either BMI, trunk lean mass, or trunk fat mass. The magnitude of effect relating TBS and LS-VBMD also decreased with increasing BMI (interaction, p = 0.090) and increasing trunk lean mass (interaction, p = 0.001), but not with increasing trunk fat mass (interaction, p = 0.224). In summary, the strength of the association between TBS and LS-VBMD among older men was variable and dependent on BMI and body composition, particularly trunk lean mass. The clinical utility of TBS among older men may be somewhat limited among men with high BMI or high trunk lean mass. © 2016 American Society for Bone and Mineral Research

Association of Trabecular Bone Score (TBS) With Incident Clinical and Radiographic Vertebral Fractures Adjusted for Lumbar Spine BMD in Older Men: A Prospective Cohort Study.

The association of trabecular bone score (TBS) with incident clinical and radiographic vertebral fractures in older men is uncertain. TBS was estimated from baseline spine dual-energy X-ray absorptiometry (DXA) scans for 5831 older men (mean age 73.7 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study. Cox proportional hazard models were used to determine the association of TBS (per 1 SD decrease) with incident clinical vertebral fractures. Logistic regression was used to determine the association between TBS (per 1 SD decrease) and incident radiographic vertebral fracture among the subset of 4309 men with baseline and follow-up lateral spine radiographs (mean 4.6 years later). We also examined whether any associations varied by body mass index (BMI) category. TBS was associated with a 1.41-fold (95% confidence interval [CI] 1.23 to 1.63) higher aged-adjusted odds of incident radiographic fracture, and this relationship did not vary by BMI (p value = 0.22 for interaction term). This association was no longer significant with further adjustment for lumbar spine bone mineral density (BMD; odds ratio [OR] = 1.11, 95% CI 0.94 to 1.30). In contrast, the age-adjusted association of TBS with incident clinical vertebral fracture was stronger in men with lower BMI (≤ median value of 26.8 kg/m2 ; hazard ratio [HR] = 2.28, 95% CI 1.82 to 2.87) than in men with higher BMI (> median; HR = 1.60, 95% CI 1.31 to 1.94; p value = 0.0002 for interaction term). With further adjustment for lumbar spine BMD, the association of TBS with incident clinical vertebral fracture was substantially attenuated in both groups (HR = 1.30 [95% CI 0.99 to 1.72] among men with lower BMI and 1.11 [95% CI 0.87 to 1.41] among men with higher BMI). In conclusion, TBS is not associated with incident clinical or radiographic vertebral fracture after consideration of age and lumbar spine BMD, with the possible exception of incident clinical vertebral fracture among men with lower BMI. © 2017 American Society for Bone and Mineral Research

The Association Between Objectively Measured Physical Activity and Subsequent Health Care Utilization in Older Men.

BACKGROUND:To examine the associations between objective physical activity measures and subsequent health care utilization. METHODS:We studied 1,283 men (mean age 79.1 years, SD 5.3) participating in the Osteoporotic Fractures in Men Study. Participants wore a SenseWear® Pro Armband monitor for 1 week. Data was summarized as daily (i) step counts, (ii) total energy expenditure, (iii) active energy expenditure, and (iv) activity time (sedentary, ≥ light, ≥ moderate). The outcome measures of 1-year hospitalizations/duration of stay from Medicare data were analyzed with a two-part hurdle model. Covariates included age, clinical center, body mass index, marital status, depressive symptoms, medical conditions, cognitive function, and prior hospitalization. RESULTS:Each 1 SD = 3,092 step increase in daily step count was associated with a 34% (95% confidence interval [CI]: 19%-46%) lower odds of hospitalization in base model (age and center) and 21% (95% CI: 4%-35%) lower odds of hospitalization in fully adjusted models. Similar but smaller associations held for other physical activity measures, but these associations were not significant in fully adjusted models. Among those hospitalized, higher step count was associated with shorter total duration of acute/postacute care stays in the base model only. There was a fourfold significant difference (from model-based estimates) in predicted care days comparing those with 2,000 versus 10,000 daily steps in the base model, but only a twofold difference (not significant) in the full model. CONCLUSION:Daily step count is an easily determined measure of physical activity that may be useful in assessment of future health care burden in older men

The Association Between Objectively Measured Physical Activity and Subsequent Health Care Utilization in Older Men.

BACKGROUND:To examine the associations between objective physical activity measures and subsequent health care utilization. METHODS:We studied 1,283 men (mean age 79.1 years, SD 5.3) participating in the Osteoporotic Fractures in Men Study. Participants wore a SenseWear® Pro Armband monitor for 1 week. Data was summarized as daily (i) step counts, (ii) total energy expenditure, (iii) active energy expenditure, and (iv) activity time (sedentary, ≥ light, ≥ moderate). The outcome measures of 1-year hospitalizations/duration of stay from Medicare data were analyzed with a two-part hurdle model. Covariates included age, clinical center, body mass index, marital status, depressive symptoms, medical conditions, cognitive function, and prior hospitalization. RESULTS:Each 1 SD = 3,092 step increase in daily step count was associated with a 34% (95% confidence interval [CI]: 19%-46%) lower odds of hospitalization in base model (age and center) and 21% (95% CI: 4%-35%) lower odds of hospitalization in fully adjusted models. Similar but smaller associations held for other physical activity measures, but these associations were not significant in fully adjusted models. Among those hospitalized, higher step count was associated with shorter total duration of acute/postacute care stays in the base model only. There was a fourfold significant difference (from model-based estimates) in predicted care days comparing those with 2,000 versus 10,000 daily steps in the base model, but only a twofold difference (not significant) in the full model. CONCLUSION:Daily step count is an easily determined measure of physical activity that may be useful in assessment of future health care burden in older men