Emerging evidence suggests muscle depletion predicts survival of patients with cancer.
At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N = 1,473) were assessed at ...presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models.
Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P < .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P < .001).
CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.
IMPORTANCE: Little is known about functional trajectories of older persons in the year before and after admission to the intensive care unit (ICU) or how pre-ICU functional trajectories affect ...post-ICU functional trajectories and death. OBJECTIVES: To characterize functional trajectories in the year before and after ICU admission and to evaluate the associations among pre-ICU functional trajectories and post-ICU functional trajectories, short-term mortality, and long-term mortality. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 754 community-dwelling persons 70 years or older, conducted between March 23, 1998, and December 31, 2012, in greater New Haven, Connecticut. The analytic sample included 291 participants who had at least 1 admission to an ICU through December 2011. MAIN OUTCOMES AND MEASURES: Functional trajectories in the year before and after an ICU admission based on 13 basic, instrumental, and mobility activities. Additional outcomes included short-term (30 day) and long-term (1 year) mortality. RESULTS: The mean (SD) age of participants was 83.7 (5.5) years. Three distinct pre-ICU functional trajectories identified were minimal disability (29.6%), mild to moderate disability (44.0%), and severe disability (26.5%). Seventy participants (24.1%) experienced early death, defined as death in the hospital (50 participants 17.2%) or death after hospital discharge but within 30 days of admission (20 participants 6.9%). Among the remaining 221 participants, 3 distinct post-ICU functional trajectories identified were minimal disability (20.8%), mild to moderate disability (28.1%), and severe disability (51.1%). More than half of the participants (53.4%) experienced functional decline or early death after critical illness. The pre-ICU functional trajectories of mild to moderate disability and severe disability were associated with more than double (adjusted hazard ratio HR, 2.41; 95% CI, 1.29-4.50) and triple (adjusted HR, 3.84; 95% CI, 1.84-8.03) the risk of death within 1 year of ICU admission, respectively. Other factors associated with 1-year mortality included ICU length of stay (adjusted HR, 1.03; 95% CI, 1.00-1.05), mechanical ventilation (adjusted HR, 2.89; 95% CI, 1.91-4.37), and shock (adjusted HR, 2.68; 95% CI, 1.63-4.38). CONCLUSIONS AND RELEVANCE: Among older persons with critical illness, more than half died within 1 month or experienced significant functional decline over the following year, with particularly poor outcomes in those who had high levels of premorbid disability. These results may help to inform discussions about prognosis and goals of care before and during critical illness.
CONTEXT Disability among older persons is a complex and highly dynamic process, with high rates of recovery and frequent transitions between states of disability. The role of intervening illnesses ...and injuries (ie, events) on these transitions is uncertain. OBJECTIVES To evaluate the relationship between intervening events and transitions among states of no disability, mild disability, severe disability, and death and to determine the association of physical frailty with these transitions. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study conducted in greater New Haven, Connecticut, from March 1998 to December 2008 of 754 community-living persons aged 70 years or older who were nondisabled at baseline in 4 essential activities of daily living: bathing, dressing, walking, and transferring. Telephone interviews were completed monthly for more than 10 years to assess disability and ascertain exposure to intervening events, which included illnesses and injuries leading to either hospitalization or restricted activity. Physical frailty (defined as gait speed >10 seconds on the rapid gait test) was assessed every 18 months through 108 months. MAIN OUTCOME MEASURE Transitions between no disability, mild disability, and severe disability and 3 transitions from each of these states to death, evaluated each month. RESULTS Hospitalization was strongly associated with 8 of the 9 possible transitions, with increased multivariable hazard ratios (HRs) as high as 168 (95% confidence interval CI, 118-239) for the transition from no disability to severe disability and decreased HRs as low as 0.41 (95% CI, 0.30-0.54) for the transition from mild disability to no disability. Restricted activity also increased the likelihood of transitioning from no disability to both mild and severe disability (HR, 2.59; 95% CI, 2.23-3.02; and HR, 8.03; 95% CI, 5.28-12.21), respectively, and from mild disability to severe disability (HR, 1.45; 95% CI, 1.14-1.84), but was not associated with recovery from mild or severe disability. For all 9 transitions, the presence of physical frailty accentuated the associations of the intervening events. For example, the absolute risk of transitioning from no disability to mild disability within 1 month after hospitalization for frail individuals was 34.9% (95% CI, 34.5%-35.3%) vs 4.9% (95% CI, 4.7%-5.1%) for nonfrail individuals. Among the possible reasons for hospitalization, fall-related injury conferred the highest likelihood of developing new or worsening disability. CONCLUSIONS Among older persons, particularly those who were physically frail, intervening illnesses and injuries greatly increased the likelihood of developing new or worsening disability. Only the most potent events, ie, those leading to hospitalization, reduced the likelihood of recovery from disability.
Comyns, TM, Murphy, J, and O'Leary, D. Reliability, usefulness, and validity of field-based vertical jump measuring devices. J Strength Cond Res 37(8): 1594-1599, 2023-The purpose of this study was ...to examine the test-retest reliability, usefulness, and validity of field-based devices, in determining jump height (JH) during a countermovement jump (CMJ). Twenty-one male (22.8 ± 2.4 years; 1.82 ± 0.07 m; 86.0 ± 10.4 kg) and 7 female field sport athletes (20.5 ± 1.5 years; 1.65 ± 0.06 m; 65.4 ± 7.2 kg) performed 3 CMJs with data simultaneously recorded using a force plate (criterion measure), Optojump, Output Capture, and Push-Band 2.0. Reliability was determined by intraclass correlation (ICC) and coefficient of variation (CV) analyses. Usefulness was assessed by comparing typical error (TE) with the smallest worthwhile change (SWC), and the validity analyses involved repeated measures analysis of variance with post hoc analysis, Pearson correlation coefficient ( r ), coefficient of determination, and Bland-Altman 95% limits of agreement analyses. All 3 field-based devices were deemed reliable in assessing CMJ height as the respective ICCs ≥ 0.80 and the CV ≤ 10%. Only the Optojump and Output Capture devices were rated as "good" at detecting the SWC in performance (Optojump SWC: 1.44 > TE: 1.04; Output Capture SWC: 1.47 > TE: 1.05). The Output Capture device demonstrated acceptable validity for CMJ height assessment, whereas the Push-Band 2.0 showed systematic bias when compared with the criterion force plate data. Systematic difference was also evident for the Optojump potentially due to the optical switching-cell position on the Optojump. Although all 3 devices showed excellent reliability, the Optojump and Output Capture devices offer practitioners a cost effective, reliable, and valid method of assessing the smallest worthwhile change in CMJ performance in an applied setting.
Frailty is a strong indicator of vulnerability among older persons, but its association with ICU outcomes has not been evaluated prospectively (ie, with objective measurements obtained prior to ICU ...admission). Our objective was to prospectively evaluate the relationship between frailty and post-ICU disability, incident nursing home admission, and death.
The parent cohort included 754 adults aged ≥ 70 years, who were evaluated monthly for disability in 13 functional activities and every 18 months for frailty (1998-2014). Frailty was assessed using the Fried index, where frailty, prefrailty, and nonfrailty were defined, respectively, as at least three, one or two, and zero criteria (of five). The analytic sample included 391 ICU admissions.
The mean age was 84.0 years. Frailty and prefrailty were present prior to 213 (54.5%) and 140 (35.8%) of the 391 admissions, respectively. Relative to nonfrailty, frailty was associated with 41% greater disability over the 6 months following a critical illness (adjusted risk ratio, 1.41; 95% CI, 1.12-1.78); prefrailty conferred 28% greater disability (adjusted risk ratio, 1.28; 95% CI, 1.01-1.63). Frailty (odds ratio, 3.52; 95% CI, 1.23-10.08), but not prefrailty (odds ratio, 2.01; 95% CI, 0.77-5.24), was associated with increased nursing home admission. Each one-point increase in frailty count (range, 0-5) was associated with double the likelihood of death (hazard ratio, 2.00; 95% CI, 1.33-3.00) through 6 months of follow-up.
Pre-ICU frailty status was associated with increased post-ICU disability and new nursing home admission among ICU survivors, and death among all admissions. Pre-ICU frailty status may provide prognostic information about outcomes after a critical illness.
Little is known about the reproductive effects of paternal cannabis exposure. We evaluated associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA methylation in sperm ...from humans and rats, respectively. DNA methylation, measured by reduced representation bisulfite sequencing, differed in the sperm of human users from non-users by at least 10% at 3,979 CpG sites. Pathway analyses indicated Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02). These same two pathways were also enriched with genes having altered methylation in sperm from THC-exposed versus vehicle-exposed rats (p < 0.01). Data validity is supported by significant correlations between THC exposure levels in humans and methylation for 177 genes, and substantial overlap in THC target genes in rat sperm (this study) and genes previously reported as having altered methylation in the brain of rat offspring born to parents both exposed to THC during adolescence. In humans, cannabis use was also associated with significantly lower sperm concentration. Findings point to possible pre-conception paternal reproductive risks associated with cannabis use.
During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ...ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes.
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