Shorter Telomere Length Is Associated With Older Age, Poor Sleep Hygiene, and Orthopedic Injury, but Not Mild Traumatic Brain Injury, in a Cohort of Canadian Children.

BACKGROUND: Predicting recovery following pediatric mild traumatic brain injury (mTBI) remains challenging. The identification of objective biomarkers for prognostic purposes could improve clinical outcomes. Telomere length (TL) has previously been used as a prognostic marker of cellular health in the context of mTBI and other neurobiological conditions. While psychosocial and environmental factors are associated with recovery outcomes following pediatric mTBI, the relationship between these factors and TL has not been investigated. This study sought to examine the relationships between TL and psychosocial and environmental factors, in a cohort of Canadian children with mTBI or orthopedic injury (OI). METHODS: Saliva was collected at a postacute (median 7 days) timepoint following injury to assess TL from a prospective longitudinal cohort of children aged 8 to 17 years with either mTBI (n = 202) or OI (n = 90), recruited from 3 Canadian sites. Questionnaires regarding psychosocial and environmental factors were obtained at a postacute follow-up visit and injury outcomes were assessed at a 3-month visit. Univariable associations between TL and psychosocial, environmental, and outcome variables were assessed using Spearman's correlation. Further adjusted analyses of these associations were performed by including injury group, age, sex, and site as covariates in multivariable generalized linear models with a Poisson family, log link function, and robust variance estimates. RESULTS: After adjusting for age, sex, and site, TL in participants with OI was 7% shorter than those with mTBI (adjusted mean ratio = 0.93; 95% confidence interval, 0.89-0.98; P = .003). As expected, increasing age was negatively associated with TL (Spearman's r = -0.14, P = .016). Sleep hygiene at 3 months was positively associated with TL (adjusted mean ratio = 1.010; 95% confidence interval, 1.001-1.020; P = .039). CONCLUSION: The relationships between TL and psychosocial and environmental factors in pediatric mTBI and OI are complex. TL may provide information regarding sleep quality in children recovering from mTBI or OI; however, further investigation into TL biomarker validity should employ a noninjured comparison group.

White matter microstructure predicts longitudinal social cognitive outcomes after paediatric traumatic brain injury: a diffusion tensor imaging study.

BACKGROUND: Deficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes. METHODS: The sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes. RESULTS: Whole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP. CONCLUSIONS: Abnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.

Diffusion MRI Microstructural Abnormalities at Term-Equivalent Age Are Associated with Neurodevelopmental Outcomes at 3 Years of Age in Very Preterm Infants.

BACKGROUND AND PURPOSE: Microstructural white matter abnormalities on DTI using Tract-Based Spatial Statistics at term-equivalent age are associated with cognitive and motor outcomes at 2 years of age or younger. However, neurodevelopmental tests administered at such early time points are insufficiently predictive of mild-moderate motor and cognitive impairment at school age. Our objective was to evaluate the microstructural antecedents of cognitive and motor outcomes at 3 years' corrected age in a cohort of very preterm infants. MATERIALS AND METHODS: We prospectively recruited 101 very preterm infants (<32 weeks' gestational age) and performed DTI at term-equivalent age. The Differential Ability Scales, 2nd ed, Verbal and Nonverbal subtests, and the Bayley Scales of Infant and Toddler Development, 3rd ed, Motor subtest, were administered at 3 years of age. We correlated DTI metrics from Tract-Based Spatial Statistics with the Bayley Scales of Infant and Toddler Development, 3rd ed, and the Differential Ability Scales, 2nd ed, scores with correction for multiple comparisons. RESULTS: Of the 101 subjects, 84 had high-quality DTI data, and of these, 69 returned for developmental testing (82%). Their mean (SD) gestational age was 28.4 (2.5) weeks, and birth weight was 1121.4 (394.1) g. DTI metrics were significantly associated with Nonverbal Ability in the corpus callosum, posterior thalamic radiations, fornix, and inferior longitudinal fasciculus and with Motor scores in the corpus callosum, internal and external capsules, posterior thalamic radiations, superior and inferior longitudinal fasciculi, cerebral peduncles, and corticospinal tracts. CONCLUSIONS: We identified widespread microstructural white matter abnormalities in very preterm infants at term that were significantly associated with cognitive and motor development at 3 years' corrected age.

Chronic kidney disease among Aboriginal people living in Canada.

AIMS: Chronic kidney disease (CKD) poses a significant health burden on Aboriginal communities around the world. High rates of diabetes among Aboriginal Canadians are an important contributing factor to the rising rates of CKD in this population, and diabetes has been the leading cause of kidney failure among Aboriginal patients initiating dialysis in Canada for the last decade. This paper will describe access to, quality of, and outcomes associated with the renal care of Aboriginal people living in Canada. RESULTS: Research shows that rates of CKD are higher among Aboriginal people residing in Canada, and that despite remote residence location, use of peritoneal dialysis is substantially lower than in white patients. Similarly, although mortality rates among Canadian hemodialysis patients are similar for Aboriginals and for whites, Aboriginal patients have substantially reduced access to kidney transplantation. CONCLUSIONS: A concerted effort to lower rates of CKD in this population is needed. Changes in healthcare policy that successfully translate into healthcare provider and patient level improvements in access to and the quality of care will be needed to significantly reduce the risk of CKD and progression to kidney failure.

Deviation from developmentally appropriate self-care autonomy. Association with diabetes outcomes.

OBJECTIVE: Treatment of IDDM in youth emphasized balancing children's self-care autonomy with their psychological maturity. However, few data exist to guide clinicians or parents, and little is known about correlates of deviations from this ideal. RESEARCH DESIGN AND METHODS: In this cross-sectional study, IDDM self-care autonomy of 100 youth was assessed using two well-validated measures. Three measures of psychological maturity (cognitive function, social-cognitive development, and academic achievement) were also collected for each child. Composite indexes of self-care autonomy and of psychological maturity were formed, and the ratio of the self-care autonomy index to the psychological maturity index quantified each child's deviation from developmentally appropriate IDDM self-care autonomy. Based on these scores, participants were categorized as exhibiting constrained (lower tertile), appropriate (middle tertile), or excessive (higher tertile) self-care autonomy. Between-group differences in treatment adherence, diabetes knowledge, glycemic control, and hospitalization rates were explored. RESULTS: Analysis of covariance controlling for age revealed that the excessive self-care autonomy group demonstrated less favorable treatment adherence, diabetes knowledge, hospitalization rates, and, marginally, glycemic control. Excessive self-care autonomy increased with age and was less common among intact two-parent families but was unrelated to other demographic factors. CONCLUSIONS: The findings indicate caution about encouragement of maximal self-care autonomy among youth with IDDM and suggest that families who succeed in maintaining parental involvement in diabetes management may have better outcomes.

Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)

The household economic burden of non-communicable diseases in 18 countries

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. METHODS: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. RESULTS: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. CONCLUSIONS: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs. (AU)

Family burden and adaptation during the initial year after traumatic brain injury in children.

OBJECTIVE: Traumatic brain injury (TBI) often leads to long-term behavioral and cognitive deficits in children. However, little is known about the burden and psychosocial morbidity of pediatric TBI for families. The purpose of this study was to test the hypothesis that moderate and severe TBI in children has more adverse consequences than orthopedic trauma. DESIGN: The sample was comprised of children between the ages of 6 and 12 recruited from hospital trauma and inpatient units including 53 with severe TBI, 56 with moderate TBI, and 80 with orthopedic injuries not involving central nervous system insult. Measures of injury-related burden, parental distress, and family functioning were administered to the child's primary caregiver at baseline assessment conducted soon after injury and at 6- and 12-month follow-ups. Multivariate repeated measures analysis of covariance was used to examine group differences in these outcomes over time. RESULTS: Caregivers in the severe TBI group reported significantly higher levels of family burden, injury-related stress, and parental psychological symptoms than caregivers in the orthopedic injury group (ORTHO). The groups did not differ with respect to marital distress. Caregivers in the severe TBI group were significantly more likely than caregivers in the ORTHO group to exceed the clinical cutoff on the Brief Symptom Inventory and to report clinically significant levels of family dysfunction at follow-up. CONCLUSIONS: The findings suggest that severe TBI is a source of considerable caregiver morbidity, even when compared with other traumatic injuries. Caregivers in the severe TBI group had persistent stress associated with the child's injury, as well as the reactions of other family members, and a relative risk of clinically significant psychological symptoms nearly twice that of the ORTHO comparison group. These findings underscore the need for interventions that facilitate family adaptation after pediatric TBI.

Influences on first-year recovery from traumatic brain injury in children.

This study examined recovery over the first year following traumatic brain injury (TBI) in children 6-12 years of age. Forty-two children with severe TBI and 52 with moderate TBI were compared to 58 children with orthopedic injuries. The children and their families were evaluated at a baseline assessment and at 6- and 12-month follow-ups. Findings documented cognitive, achievement, and behavioral sequelae of TBI, with only limited evidence for recovery over the first year postinjury. Outcomes were predicted by preinjury factors, TBI severity, and measures of the postinjury family environment. Some of the sequelae of severe TBI were more marked in the context of higher compared with lower levels of family burden or dysfunction. The findings confirm the need to consider environmental contributions to outcomes of TBI in children.

The relationship of caregiver coping to family outcomes during the initial year following pediatric traumatic injury.

This study identified coping strategies associated with caregiver outcomes following pediatric injury and examined injury type as a moderator of coping efficacy. Families of 103 children with traumatic brain injury (TBI) and 71 children with orthopedic injuries were followed prospectively during the initial year postinjury. The groups had comparable preinjury characteristics and hospitalization experiences but differed on neurological insult. In hierarchical regression analyses, acceptance was associated with lower burden and denial was associated with greater distress in both groups. Active coping resulted in higher distress following TBI but not orthopedic injuries. Conversely, the use of humor was related to diminishing distress following TBI but unrelated to distress following orthopedic injuries. Results are discussed in terms of the implications for intervention following TBI.

Prevalence and correlates of depressive symptoms following traumatic brain injuries in children.

The prevalence and correlates of depressive symptoms following childhood traumatic brain injuries (TBI) were examined using data drawn from a prospective longitudinal study. Participants included 38 children with severe TBI, 51 with moderate TBI, and 55 with orthopedic injuries (OI). Assessments occurred shortly after injury (baseline) and at 6- and 12-month follow-ups. Children completed the Child Depression Inventory (CDI). Parents rated depressive symptoms using the Child Behavior Checklist (CBC), with baseline ratings reflecting premorbid status. Assessments also included measures of children's neurocognitive functioning and the family environment. The three groups did not differ overall in self-reported symptoms on the CDI, but did display different trends over time. The three groups did not differ on parent ratings of premorbid depressive symptoms on the CBC, but parents reported more depressive symptoms in the TBI groups than in the OI group at 6- and 12-month follow-ups. Child and parent reports were correlated for children in the TBI groups, but not for those in the OI group. Depressive symptoms were related to socioeconomic status in all groups. Socioeconomic status also was a significant moderator of group differences, such that the effects of TBI were exacerbated in children from more disadvantaged homes. Although self-reports of depressive symptoms were related inconsistently to children's verbal memory, parent reports of depressive symptoms were unrelated to IQ or verbal memory. The findings suggest that TBI increases the risk of depressive symptoms, especially among more socially disadvantaged children, and that depressive symptoms are not strongly related to post-injury neurocognitive deficits.

Childhood traumatic brain injury: initial impact on the family.

Traumatic brain injury (TBI) is a significant source of morbidity and mortality in children, resulting in a wide range of cognitive and behavioral sequelae. However, little is known about the effects of pediatric TBI and its aftermath on families. The current investigation examined the impact of TBI on families during the first month following injury. Children with orthopedic injuries requiring hospitalization served as a control group. The sample consisted of 44 families of children of severe TBI, 52 families of children with moderate TBI, and 69 families of children with orthopedic injuries not involving the central nervous system (CNS). Families of children with severe TBI experienced significantly more injury-related stress than the other two groups of families. Parents of children with TBI also reported higher levels of psychological symptoms than parents of children with orthopedic injuries. Findings from regression analyses suggested that families facing multiple stressors in addition to the injury and those who cope poorly may be at greatest risk for adverse consequences. Future interventions could provide anticipatory guidance and support to at-risk families.

Performance of children with traumatic brain injury on the Cognitive Assessment System.

Children and adolescents with traumatic brain injury (TBI) were compared to a matched sample of neurologically normal children and adolescents on several measures of cognitive processing. Each of the children in the TBI group had experienced a closed head injury of moderate to severe magnitude. Participants in both the TBI (n = 22) and control (n = 22) groups ranged in age from 9 to 17 years and lived in the midwestern United States. They were all administered the Cognitive Assessment System (Naglieri & Das, 1997a). Children with TBI earned significantly lower scores in the domains of Planning and Attention than the matched control group. Within-group comparisons showed that the TBI group s Planning and Attention scores were significantly lower than their Simultaneous and Successive scores. The results are consistent with previous literature demonstrating poor performance on measures of attention and executive functions among children who have experienced TBI.

Aboriginal patients on the road to kidney transplantation: is residence location a barrier?

Aboriginal dialysis patients have reduced access to kidney transplantation. The reasons for this disparity are unknown. Tonelli et al. show that in Canada, residence location does not significantly impact on an Aboriginal dialysis patient's likelihood of receiving kidney transplantation. This Commentary explores the issue of decreased access and examines issues surrounding the findings of Tonelli et al.

Acute and chronic neuropsychological consequences of mercury vapor poisoning in two early adolescents.

Mercury is an extremely toxic heavy metal that can devastate the central nervous system. The neuropsychological consequences of mercury vapor intoxication have been studied primarily in adults. We present two adolescent half-siblings, ages 13 and 15, who were unintentionally exposed to concentrated mercury vapor for 3 months. Both children participated in neuropsychological evaluations shortly after being diagnosed with mercury toxicity, and again 1 year later. Results from the initial assessments documented functional deficits consistent with diffuse encephalopathy. Upon follow-up, neuropsychological functioning had improved, but deficits remained in visuoperceptual and constructional skills, nonverbal memory, and conceptual abstraction. The deficits persisted despite removal from exposure, return of urinary and blood mercury to acceptable levels, and resolution of neuropsychiatric symptoms. The deficits were similar to, but more severe than, those found in adults suffering from mercury vapor intoxication. The results suggest that the developing brain may be especially vulnerable to mercury vapor toxicity.

Predicting premorbid neuropsychological functioning following pediatric traumatic brain injury.

This study examined the prediction of premorbid neuropsychological functioning using data from an ongoing prospective study of traumatic brain injuries (TBI) in children ages 6 to 12 years. Prediction equations were derived based on 80 children with orthopedic injuries (OI), who served as a comparison group for the children with TBI. Collectively, parent ratings of premorbid school performance, maternal ethnicity, family socioeconomic status, and children's word recognition skill predicted from 13% to 45% of the variance in three measures of neuropsychological functioning. The regression equations were used to compute predicted scores among 109 children with TBI. Actual scores fell significantly below predicted scores among children with TBI, and the magnitude of the deficits was correlated with injury severity. Premorbid neuropsychological functioning can be predicted in children with TBI, but with less precision than would be desirable for clinical purposes.

Neuropsychological correlates of learning disability subtypes in children with Tourette's syndrome.

Neuropsychological deficits in Tourette's syndrome (TS) may be associated with learning disabilities. We examined the neuropsychological performance of 70 children with TS between the ages 6 and 18 years who were classified into four groups based on their pattern of performance on the Wide Range Achievement Test-Revised. The groups included three learning disability subtypes and a nonlearning disabled comparison group. The groups differed significantly on several measures in a comprehensive neuropsychological test battery. The pattern of differences was not entirely consistent with previous research, however, suggesting that neuropsychological correlates of learning disabilities may be influenced by the specific pathophysiology associated with TS. Thus, previous research on the neuropsychology of learning disability subtypes might not be generalizable to children with discrete neuropsychiatric disorders such as TS.

On being called "mentally retarded": do developmental and professional perspectives limit labeling effects?

When children are labeled "mentally retarded," adults sometimes respond to their failures in ways that stimulate learned helplessness. The generalizability of such labeling effects was assessed in this study. Participants were four groups of adults that varied in professional experience with retarded children: within each group, some subjects subscribed to the developmental position (that retarded and nonretarded children have similar reasoning and learning capacities when matched for mental age) and some to the difference position (that retarded children lag behind their nonretarded peers in such capacities even when matched for mental age) of mental retardation. All subjects made judgments about the failure of a "retarded" and an unlabeled child. Strong labeling effects were found among proponents of the difference position but not among proponents of the developmental position, as well as among those groups with relatively little professional experience. Results suggest that beliefs consistent with the developmental position and experience with retarded children both attenuate the potentially helplessness-inducing effects of the mentally retarded label.