Examining the Influence of Early-Life and Recent Traumatic Events on Loneliness in Centenarians.

Early-life traumatic experiences have lasting implications for late-life socio-emotional development, contributing to a greater prevalence of poor mental health in very old age. The purpose of this study was to examine the influence of early-life and recent traumatic life experiences on loneliness among centenarians. A total of 154 centenarians participated in a semistructured interview. The time of traumatic occurrence and type of trauma experienced influence loneliness in centenarians. Experiencing a natural disaster 70 or more years ago significantly predicted loneliness. Terror management theory proposes that coming to terms with one's mortality represents an underlying source of anxiety that can influence human behavior to create both immediate and future defenses. Evidence from this study can be used to improve how aging service practitioners integrate reminiscence or life-review therapy or counseling within clinical or educational settings.

Previous aminoglycoside use and acute kidney injury risk in non-critically ill children.

OBJECTIVES: Aminoglycosides (AG) are a group of bactericidal antibiotics with nephrotoxic effects that are commonly used in the treatment of hospitialized children. We have examined previous AG treatment as a risk factor for acute kidney injury (AKI) during current AG treatment. STUDY DESIGN: We performed a retrospective cohort study of children ranging in age from 1 month to 18 years who were treated with AG between October 2008 and April 2012 at Montreal's Children's Hospital. Children for whom no serum creatinine data (SCr) were available and those with baseline renal disease were excluded from the analysis. Main exposures were prior AG use (number and hours of prior treatments) and time since last AG treatment. The main outcome was AKI, defined on the basis of the Kidney Disease: Improving Global Outcomes guidelines. Logistic regression was used to examine exposure-outcome associations. RESULTS: AG treatments episodes with Stage 1, 2, and 3 AKI, respectively, were associated with a median of 98 [interquartile range (IQR) 339], 231 (IQR 688), and 111 (IQR 505) h of prior AG treatment, respectively, versus non-AKI (median 0, IQR 54 h) (p < 0.0001). AKI episodes were associated with a mean (± standard deviation) of 1.5 ± 1.8 AG treatments in the previous 6 months, versus 0.9 ± 1.6 AG treatments for non-AKI. The number of AG-treatment days during the preceding 6 months [adjusted odds ratio (adjOR) 1.04, 95 % confidence interval (CI) 1.03-1.06; p < 0.001], younger age (adjOR 0.96, 95 % CI 0.93-0.99; p = 0.009), admission to hematology-oncology department (adjOR 3.88, 95 % CI 2.17-6.96; p < 0.001), and tobramycin use (adjOR 1.77, 95 % CI 1.04-3.02; p = 0.04) were independently associated with AKI. Episodes with Stage 1 and 2 AKI were associated with fewer days since last treatment compared to non-AKI treatment (p < 0.02 and p < 0.005, respectively; Mann-Whitney test). CONCLUSIONS: Based on these results, prior AG treatment is a risk factor for AKI and should be considered when dosing and monitoring hospitalized children being treated with AG.

Serum cystatin C for acute kidney injury evaluation in children treated with aminoglycosides.

BACKGROUND: Serum cystatin C (CysC) is a more accurate glomerular filtration rate marker than serum creatinine (SCr) and may rise more quickly with acute kidney injury (AKI). METHODS: We performed a prospective cohort study of 81 non-critically ill children during 110 aminoglycoside (AG) treatments. We calculated area under the curve (AUC) for CysC to diagnose SCr-defined AKI and predict persistent AKI. SCr-AKI definition was based on the Kidney Disease: Improving Global Outcomes (≥stage 1: ≥50 % or 26.5 µmol/l SCr rise from baseline; stage 2: SCr doubling); CysC-AKI was based on a modified version using CysC rise. RESULTS: SCr-AKI and CysC-AKI developed in 45 and 48 % treatments, respectively. CysC rise predicted stage 1 (AUC = 0.75, 95 % CI 0.60-0.90) and 2 (AUC = 0.85, 95 % CI 0.75-0.95) SCr-AKI 2 days before SCr-AKI attainment. The best combined sensitivity/specificity for percent CysC rise to predict stage 1 SCr-AKI was with a 44 % CysC rise (sensitivity = 65 %, specificity = 83 %). CysC rise on day of SCr-AKI development was associated with SCr-AKI ≥48 h (AUC = 0.73, 95 % CI 0.56-0.90) and ≥50 % persistent SCr rise at treatment end (AUC = 0.76, 95 % CI 0.61-0.90). CONCLUSIONS: CysC is as an early AKI biomarker and predictive of persistent AKI on aminoglycoside treatment.

Loss of α-calcitonin gene-related peptide (αCGRP) reduces the efficacy of the Vestibulo-ocular Reflex (VOR).

The neuroactive peptide calcitonin-gene related peptide (CGRP) is known to act at efferent synapses and their targets in hair cell organs, including the cochlea and lateral line. CGRP is also expressed in vestibular efferent neurons as well as a number of central vestibular neurons. Although CGRP-null (-/-) mice demonstrate a significant reduction in cochlear nerve sound-evoked activity compared with wild-type mice, it is unknown whether and how the loss of CGRP influence vestibular system function. Vestibular function was assessed by quantifying the vestibulo-ocular reflex (VOR) in alert mice. The loss of CGRP in (-/-) mice was associated with a reduction of the VOR gain of ≈50% without a concomitant change in phase. Using immunohistochemistry, we confirmed that, although CGRP staining was absent in the vestibular end-organs of null (-/-) mice, cholinergic staining appeared normal, suggesting that the overall gross development of vestibular efferent innervation was unaltered. We further confirmed that the observed deficit in vestibular function of null (-/-) mice was not the result of nontargeted effects at the level of the extraocular motor neurons and/or their innervation of extraocular muscles. Analysis of the relationship between vestibular quick phase amplitude and peak velocity revealed that extraocular motor function was unchanged, and immunohistochemistry revealed no abnormalities in motor endplates. Together, our findings show that the neurotransmitter CGRP plays a key role in ensuring VOR efficacy.

Immunologic Benefits of 0-antigen Mismatched Transplants: No Added Boost for Racial and Ethnic Minorities.

Background: Systemic barriers to posttransplant care, including access to immunosuppressant medications, contribute to higher rates of kidney transplant failure in racial minorities. Matching donor and recipient HLA alleles reduce allorecognition, easing reliance on immunosuppression. We hypothesize that 0-antigen mismatch transplants may provide stronger protection against graft loss in racial minorities. Methods: We compared adult, single-organ, deceased-donor kidney transplants in the United States from 2007 to 2016 by degree of HLA mismatch (0- versus ≥1-antigen mismatch). We examined time-to-allograft failure, with death as a competing event, using multivariable Weibull models, stratified by recipient race (White versus non-White), and evaluated the interaction between mismatch and recipient race. We used Kaplan-Meier imputation to account for competing risk of death. Results: We analyzed 102 114 transplants (median follow-up, 5.6 y; 16 862 graft losses, 18 994 deaths). Zero-antigen mismatch was associated with improved allograft survival (adjusted subdistribution hazard ratio [sHR] 0.80; 95% confidence interval [CI], 0.75-0.85). When stratified by recipient race, the effect of 0-antigen mismatch was more pronounced in White (unadjusted sHR 0.78; 95% CI, 0.72-0.83) versus non-White recipients (sHR 0.88; 95% CI, 0.79-0.99; interaction P = 0.04). The differential effect was attenuated after adjusting for covariates (sHR 0.78; 95% CI, 0.73-0.84 versus sHR 0.87; 95% CI, 0.77-0.98; interaction P = 0.10). Conclusions: Zero-antigen mismatch transplants conferred a 20% risk reduction in allograft loss, which was similar between non-White and White recipients. This may reflect an increased degree of mismatch at other HLA alleles and non-HLA alleles in non-White recipients or because of the extent of systemic barriers to healthcare borne by minority recipients.

Sex-related differences in mortality, acute kidney injury, and respiratory failure among critically ill patients with COVID-19.

ABSTRACT: Although the number of deaths due to coronavirus disease 2019 (COVID-19) is higher in men than women, prior studies have provided limited sex-stratified clinical data.We evaluated sex-related differences in clinical outcomes among critically ill adults with COVID-19.Multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 67 U.S. hospitals from March 4 to May 9, 2020. Multilevel logistic regression was used to evaluate 28-day in-hospital mortality, severe acute kidney injury (AKI requiring kidney replacement therapy), and respiratory failure occurring within 14 days of intensive care unit admission.A total of 4407 patients were included (median age, 62 years; 2793 [63.4%] men; 1159 [26.3%] non-Hispanic White; 1220 [27.7%] non-Hispanic Black; 994 [22.6%] Hispanic). Compared with women, men were younger (median age, 61 vs 64 years, less likely to be non-Hispanic Black (684 [24.5%] vs 536 [33.2%]), and more likely to smoke (877 [31.4%] vs 422 [26.2%]). During median follow-up of 14 days, 1072 men (38.4%) and 553 women (34.3%) died. Severe AKI occurred in 590 men (21.8%), and 239 women (15.5%), while respiratory failure occurred in 2255 men (80.7%) and 1234 women (76.5%). After adjusting for age, race/ethnicity and clinical variables, compared with women, men had a higher risk of death (OR, 1.50, 95% CI, 1.26-1.77), severe AKI (OR, 1.92; 95% CI 1.57-2.36), and respiratory failure (OR, 1.42; 95% CI, 1.11-1.80).In this multicenter cohort of critically ill adults with COVID-19, men were more likely to have adverse outcomes compared with women.

Tubular injury and cell-cycle arrest biomarkers to predict acute kidney injury in noncritically ill children receiving aminoglycosides.

Aim: NGAL, IL-18, KIM-1 as well as urinary TIMP2 and IGFBP7 and their mathematical product (TIMP2*IGFBP7) were evaluated for detecting pediatric aminoglycoside acute kidney injury (AG-AKI). Methods: In a prospective study, noncritically ill children received aminoglycosides (AG) ≥3 days. The area under the curve (AUC) for biomarkers to detect AKI was calculated by a) days before AKI onset; b) treatment days. Results: There were 113 AG episodes (68% febrile neutropenia). The AKI group had a higher proportion with febrile neutropenia. The AKI group had significantly lower NGAL 3 days before AKI, as patients with febrile neutropenia had a lower NGAL during AG treatment (p < 0.05). NGAL, IL-18 and TIMP2*IGFBP7 had AUC ≥0.73 at 3, 2 and 2 days before AKI onset. Conclusion: NGAL, IL-18 and TIMP2*IGFBP7 were modest early biomarkers of AG-AKI. Febrile neutropenia was associated with lower NGAL.

Empowerment and Resilience in Families of Adults With Intellectual and Developmental Disabilities.

Using the family resilience model, we examined the association between empowerment, family member age, length of institutionalization, and resilience among family members of relatives with intellectual and developmental disabilities (IDD) following deinstitutionalization. Participants included 56 family members whose relatives with IDD recently transitioned to community living. Results strongly indicate empowerment plays a key role in positive family adaptation. Thus, following a relative's move from an institution to the community, empowerment is a promising form of protection that holds potential to increase family resilience. The results of the current study support the family resilience model as a foundation for future research regarding how families navigate significant transitions throughout the lifespan. Implications for practice and policy are provided.

The effects of repetitive motion on lumbar flexion and erector spinae muscle activity in rowers.

OBJECTIVE: The purpose of this study was to investigate changes in lumbar flexion together with the pattern and level of muscle activity of selected erector spinae during a rowing trial.Design. Cross-sectional repeated measures design. BACKGROUND: Low back pain is a common problem in rowers. The amount of lumbar flexion occurring during rowing might influence the possibility of injury. METHODS: Sixteen young adult school rowers participated in the study. Changes in lumbar flexion and muscle activity were recorded across the drive phase, at three stages of an ergometer based rowing trial. Lumbar flexion was calculated by computerised motion analysis of surface markers attached to the spinous processes of L1 and S1. Surface electromyography techniques were used to examine the magnitude of activity from three erector spinae muscles. The median frequency of the electromyographic signal was examined to quantify fatigue in the erector spinae muscles during isometric maximal effort muscle activation prior to and after the rowing trial. RESULTS: Lumbar flexion increased significantly (P<0.05) during the rowing trial, as did the magnitude of electromyographic activity from sites over the lumbar multifidus, iliocostalis lumborum and longissimus thoracis muscles. The median frequency decreased significantly (P<0.05) in each muscle examined. CONCLUSIONS: The findings showed that rowers attain relatively high levels of lumbar flexion during the rowing stroke, and these levels are increased during the course of the rowing trial. Indirect evidence of muscle fatigue in erector spinae muscles was also apparent, and this observation may in part be responsible for the increased levels of lumbar flexion observed. RELEVANCE: Excessive lumbar flexion may influence the potential for injury to spinal structures. An awareness of increased lumbar flexion and muscle fatigue in the erector spinae muscles may be important for injury prevention programs for rowers.