Household material hardship and distress among parents of children with advanced cancer: A report from the PediQUEST Response trial.

BACKGROUND: The prevalence and characteristics of household material hardship (HMH) in families of children with advanced cancer and its association with parent distress are unknown and herein described. METHODS: Parents of children aged ≥2 years with advanced cancer at five cancer centers completed baseline surveys as part of the PediQUEST Response trial. HMH (housing, energy, and food) was operationalized as binary (≥1 HMH domains), ordinal (zero, one, or two or more HMH domains), and housing based (none, nonhousing [food and/or energy], only housing, or housing + other). Associations between HMH and parent distress measured by the State-Trait Anxiety Inventory-State and the 10-item Center for Epidemiologic Studies Depression Scale were estimated via linear models adjusting for confounders. RESULTS: Among 150 parents, 41% reported ≥1 HMH (housing, 28% [only housing, 8%; housing + other, 20%]; energy, 19%; food, 27%). HMH was more prevalent among Hispanic, other non-White race, Spanish-speaking, and single parents and those with lower education (associate degree or less) or who were uninsured/Medicaid-only insured. Parents endorsing HMH reported higher anxiety (mean difference [MD], 9.2 [95% CI, 3.7-14.7]) and depression (MD, 4.1 [95% CI, 1.7-6.5]) scores compared to those without HMH. Distress increased with the number of hardships, particularly housing insecurity. Specifically, parents experiencing housing hardship, alone or combined, reported higher distress (housing only: anxiety: MD, 10.2 [95% CI, 1.8-18.5]; depression: MD, 4.9 [95% CI, 1.3-8.6]; housing + other HMH: anxiety: MD, 12.0 [95% CI, 5.2-18.9]; depression: MD, 4.8 [95% CI, 1.8-7.8]). CONCLUSIONS: HMH is highly prevalent in pediatric advanced cancer, especially among historically marginalized families. Future research should investigate whether interventions targeting HMH, particularly housing stabilization efforts, can mitigate parent distress. PLAIN LANGUAGE SUMMARY: In our cohort of parents of children with advanced cancer, household material hardship (HMH) was highly prevalent and significantly associated with higher parent distress. Housing hardship was the primary driver of this association. Families of children with advanced cancer may benefit from systematic HMH screening as well as targeted HMH interventions, especially stabilizing housing.

Use of PDSA Cycles to Increase Aspiration Risk and Swallow Screening Documentation in the Hospitalized General Medical Patient Care Population.

BACKGROUND: Aspiration, while hospitalized, can lead to increases in length of stay and health care costs. Nurses must identify patients at risk of aspiration early to initiate appropriate precautions. LOCAL PROBLEM: An increase in-hospital patient aspirations at a Midwestern hospital prompted a review of events, which identified opportunities to improve identification of patients' risk factors and completion of the bedside swallow screening. METHODS: Interventions were identified via a causal factor tree analysis and an impact-effort grid then deployed using the Plan-Do-Study-Act (PDSA) methodology. INTERVENTIONS: Interventions deployed included game based-learning, a unit-based champion, and the use of visual cues to identify patients at risk for aspiration. RESULTS: After 3 PDSA cycles, documentation of patients' aspiration risk factors on admission increased by 40%, with a 51.3% increase in bedside swallow screening results. CONCLUSION: Iterative PDSA cycles successfully tested staff engagement strategies to improve aspiration risk and swallow screening documentation compliance.

Cannabis and tobacco use prior to pregnancy and subsequent offspring birth outcomes: a 20-year intergenerational prospective cohort study.

There is increasing evidence that the life-course origins of health and development begin before conception. We examined associations between timing and frequency of preconception cannabis and tobacco use and next generation preterm birth (PTB), low birth weight (LBW) and small for gestational age. 665 participants in a general population cohort were repeatedly assessed on tobacco and cannabis use between ages 14-29 years, before pregnancy. Associations were estimated using logistic regression. Preconception parent (either maternal or paternal) daily cannabis use age 15-17 was associated with sixfold increases in the odds of offspring PTB (aOR 6.65, 95% CI 1.92, 23.09), and offspring LBW (aOR 5.84, 95% CI 1.70-20.08), after adjusting for baseline sociodemographic factors, parent sex, offspring sex, family socioeconomic status, parent mental health at baseline, and concurrent tobacco use. There was little evidence of associations with preconception parental cannabis use at other ages or preconception parental tobacco use. Findings support the hypothesis that the early life origins of growth begin before conception and provide a compelling rationale for prevention of frequent use during adolescence. This is pertinent given liberalisation of cannabis policy.

Survival of brain tumour patients with epilepsy.

Pro-tumorigenic electrochemical synapses between neurons and brain tumour cells in preclinical studies suggest unfavourable effects of epilepsy on patient survival. We investigated associations of epilepsy and survival in three cohorts of brain tumour patients (meningioma, glioblastoma and brain metastases). Cohorts were segregated into three groups for comparative analyses: (i) no epilepsy; (ii) epilepsy without status epilepticus; and (iii) status epilepticus. Status epilepticus was considered a surrogate of extensive neuronal hyperexcitability. The main outcome was progression-free survival (meningioma) and overall survival (glioblastoma and brain metastases), adjusted for established prognostic factors and onset of epilepsy by time-dependent multivariate Cox modelling. The primary analysis population comprised 1792 patients (742 meningioma, 249 glioblastoma, 801 brain metastases). Epilepsy was associated with favourable prognostic factors. However, on multivariate analyses, status epilepticus was associated with inferior overall survival of patients with glioblastoma [status epilepticus versus no epilepsy multivariate hazard ratio (HR) 3.72, confidence interval (CI) 1.78-7.76, P < 0.001] and brain metastases (status epilepticus versus no epilepsy HR 2.30, CI 1.10-4.79, P = 0.026). Among brain metastases patients, but not among patients with meningioma or glioblastoma, epilepsy was similarly associated with inferior overall survival (epilepsy versus no epilepsy HR 2.16, CI 1.60-2.93, P < 0.001). We conclude that epilepsy may convey inferior survival of patients with malignant brain tumours.

Young-adult compared to adolescent onset of regular cannabis use: A 20-year prospective cohort study of later consequences.

INTRODUCTION: This paper compares consequences of cannabis use initiated after high school with those of cannabis initiation in adolescence, with estimates of the proportion of adverse consequences accounted for by adult-onset and adolescent-onset cannabis users. METHODS: A state-representative sample in Victoria, Australia (n = 1792) participated in a 10-wave longitudinal study and was followed from age 15 to 35 years. Exposure variable: Patterns of cannabis use across 20 years. Outcomes at age 35: Alcohol use, smoking, illicit drug use, relationship status, financial hardship, depression, anxiety and employment status. RESULTS: Substantially more participants (13.6%) initiated regular use after high school (young-adult onset) than in adolescence (7.7%, adolescent onset). By the mid-30s, both young-adult and adolescent-onset regular users were more likely than minimal/non-users (63.5%) to have used other illicit drugs (odds ratio [OR] > 20.4), be a high-risk alcohol drinker (OR > 3.7), smoked daily (OR > 7.2) and less likely to be in relationships (OR < 0.4). As the prevalence of the young-adult-onset group was nearly double of the adolescent-onset group, it accounted for a higher proportion of adverse consequences than the adolescent-onset group. DISCUSSION AND CONCLUSIONS: Cannabis users who began regular use in their teens had poorer later life outcomes than non-using peers. The larger group who began regular cannabis use after leaving high school accounted for most cannabis-related harms in adulthood. Given the legalisation of cannabis use in an increasing number of jurisdictions, we should increasingly expect harms from cannabis use to lie in those commencing use in young adulthood.

Longitudinal patterns of amphetamine use from adolescence to adulthood: A latent class analysis of a 20-year prospective study of Australians.

BACKGROUND: To examine the longitudinal patterns of amphetamine use over twenty years from adolescence to the mid-thirties; and identify adolescent antecedents of future problematic patterns of use. DESIGN: Ten-wave longitudinal study following participants from age 15 to age 35 in Victoria, Australia. Participants (N = 1755; 47% males) first enrolled in the Victoria Adolescent Health Cohort Study in 1992. MEASUREMENTS: Outcome: Self-reported frequency of amphetamine use. PREDICTORS: Gender, depression and anxiety, peer alcohol and tobacco use; self-reported alcohol, tobacco and cannabis use, self-reported adolescent antisocial behavior. FINDINGS: Three different longitudinal patterns were identified: Non-user (83.7%); Occasional user (14.5%); Regular user (1.8%). Among the two user patterns, amphetamine use was commonly initiated in late teenage years or early 20s, peaked at mid-20s, and declined substantially by mid-30s. Participants who used cannabis and had smoking peers during adolescence were at significantly more likely to become an occasional or regular user (p < .05). CONCLUSION: Regular cannabis use and peer tobacco use during adolescence were the two strongest predictors of a longitudinal pattern of regular amphetamine use in the mid-30s. This suggests that prevention programs could be implemented around or before mid-adolescence and interventions to reduce amphetamine harms focus on high-risk individuals in their 20s when amphetamine use was at its peak.

20-year outcomes in adolescents who self-harm: a population-based cohort study.

BACKGROUND: Little is known about the long-term psychosocial outcomes associated with self-harm during adolescence. We aimed to determine whether adolescents who self-harm are at increased risk of adverse psychosocial outcomes in the fourth decade of life, using data from the Victorian Adolescent Health Cohort Study. METHODS: We recruited a stratified, random sample of 1943 adolescents from 44 schools across the state of Victoria, Australia. The study started on Aug 20, 1992, and finished on March 4, 2014. We obtained data relating to self-harm from questionnaires and telephone interviews at eight waves of follow-up, commencing at mean age 15·9 years (SD 0·5; waves 3-6 during adolescence, 6 months apart) and ending at mean age 35·1 years (SD 0·6; wave 10). The outcome measures at age 35 years were social disadvantage (divorced or separated, not in a relationship, not earning money, receipt of government welfare, and experiencing financial hardship), common mental disorders such as depression and anxiety, and substance use. We assessed the associations between self-harm during adolescence and the outcome measures at 35 years (wave 10) using logistic regression models, with progressive adjustment: (1) adjustment for sex and age; (2) further adjustment for background social factors; (3) additional adjustment for common mental disorder in adolescence; and (4) final additional adjustment for adolescent antisocial behaviour and substance use measures. FINDINGS: From the total cohort of 1943 participants, 1802 participants were assessed for self-harm during adolescence (between waves 3 and 6). Of these, 1671 were included in the analysis sample. 135 (8%) reported having self-harmed at least once during adolescence. At 35 years (wave 10), mental health problems, daily tobacco smoking, illicit drug use, and dependence were all more common in participants who had reported self-harm during the adolescent phase of the study (n=135) than in those who had not (n=1536): for social disadvantage odds ratios [ORs] ranged from 1·34 (95% CI 1·25-1·43) for unemployment to 1·88 (1·78-1·98) for financial hardship; for mental health they ranged from 1·61 (1·51-1·72) for depression to 1·92 (1·79-2·04) for anxiety; for illicit drug use they ranged from 1·36 (1·25-1·49) for any amphetamine use to 3·39 (3·12-3·67) for weekly cannabis use; for dependence syndrome they were 1·72 (1·57-1·87) for nicotine dependence, 2·67 (2·38-2·99) for cannabis dependence, and 1·74 (1·62-1·86) for any dependence; and the OR for daily smoking was 2·00 (1·89-2·12). Adjustment for socio-demographic factors made little difference to these associations but a further adjustment for adolescent common mental disorders substantially attenuated most associations, with the exception of daily tobacco smoking (adjusted OR 1·74, 95% CI 1·08-2·81), any illicit drug use (1·72, 1·07-2·79) and weekly cannabis use (3·18, 1·58-6·42). Further adjustment for adolescent risky substance use and antisocial behaviour attenuated the remaining associations, with the exception of weekly cannabis use at age 35 years, which remained independently associated with self-harm during adolescence (2·27, 1·09-4·69). INTERPRETATION: Adolescents who self-harm are more likely to experience a wide range of psychosocial problems later in life. With the notable exception of heavy cannabis use, these problems appear to be largely accounted for by concurrent adolescent mental health disorders and substance use. Complex interventions addressing the domains of mental state, behaviour, and substance use are likely to be most successful in helping this susceptible group adjust to adult life. FUNDING: National Health and Medical Research Council, the Royal Children's Hospital Foundation, and the Murdoch Childrens Research Institute.

Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling.

The occurrence of cognitive disturbances upon CNS inflammation or infection has been correlated with increased levels of the cytokine tumor necrosis factor-α (TNFα). To date, however, no specific mechanism via which this cytokine could alter cognitive circuits has been demonstrated. Here, we show that local increase of TNFα in the hippocampal dentate gyrus activates astrocyte TNF receptor type 1 (TNFR1), which in turn triggers an astrocyte-neuron signaling cascade that results in persistent functional modification of hippocampal excitatory synapses. Astrocytic TNFR1 signaling is necessary for the hippocampal synaptic alteration and contextual learning-memory impairment observed in experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis (MS). This process may contribute to the pathogenesis of cognitive disturbances in MS, as well as in other CNS conditions accompanied by inflammatory states or infections.

Tumor necrosis factor (TNF)-receptor 1 and 2 mediate homeostatic synaptic plasticity of denervated mouse dentate granule cells.

Neurological diseases are often accompanied by neuronal cell death and subsequent deafferentation of connected brain regions. To study functional changes after denervation we generated entorhino-hippocampal slice cultures, transected the entorhinal pathway, and denervated dentate granule cells in vitro. Our previous work revealed that partially denervated neurons respond to the loss of input with a compensatory, i.e., homeostatic, increase in their excitatory synaptic strength. TNFα maintains this denervation-induced homeostatic strengthening of excitatory synapses. Here, we used pharmacological approaches and mouse genetics to assess the role of TNF-receptor 1 and 2 in lesion-induced excitatory synaptic strengthening. Our experiments disclose that both TNF-receptors are involved in the regulation of denervation-induced synaptic plasticity. In line with this result TNF-receptor 1 and 2 mRNA-levels were upregulated after deafferentation in vitro. These findings implicate TNF-receptor signaling cascades in the regulation of homeostatic plasticity of denervated networks and suggest an important role for TNFα-signaling in the course of neurological diseases accompanied by deafferentation.

Systemic inflammation is associated with a reduction in Synaptopodin expression in the mouse hippocampus.

Systemic inflammation is known to affect memory function through the activation of immune cells and the release of inflammatory cytokines. However, the neuronal targets by which inflammatory signaling pathways affect synaptic plasticity remain not well understood. Here, we addressed the question of whether systemic lipopolysaccharide (LPS)-induced inflammation influences the expression of Synaptopodin (SP). SP is an actin-binding protein, which is considered to control the ability of neurons to express synaptic plasticity by regulating the actin-cytoskeleton and/or intracellular Ca(2+) stores. This makes SP an interesting target molecule in the context of inflammation-induced alterations in synaptic plasticity. Using quantitative PCR (qPCR)-analysis and immunohistochemistry we here demonstrate that intraperitoneal LPS-injection in two-month old male Balb/c mice leads to a reduction in hippocampal SP-levels (area CA1; 24h after injection). These changes are accompanied by a defect in the ability to induce long-term potentiation (LTP) of Schaffer collateral-CA1 synapses, similar to what is observed in SP-deficient mice. We therefore propose that systemic inflammation could exert its effects on neural plasticity, at least in part, through the down-regulation of SP in vivo.

Tumor necrosis factor alpha maintains denervation-induced homeostatic synaptic plasticity of mouse dentate granule cells.

Neurons which lose part of their input respond with a compensatory increase in excitatory synaptic strength. This observation is of particular interest in the context of neurological diseases, which are accompanied by the loss of neurons and subsequent denervation of connected brain regions. However, while the cellular and molecular mechanisms of pharmacologically induced homeostatic synaptic plasticity have been identified to a certain degree, denervation-induced homeostatic synaptic plasticity remains not well understood. Here, we employed the entorhinal denervation in vitro model to study the role of tumor necrosis factor alpha (TNFα) on changes in excitatory synaptic strength of mouse dentate granule cells following partial deafferentation. Our experiments disclose that TNFα is required for the maintenance of a compensatory increase in excitatory synaptic strength at 3-4 days post lesion (dpl), but not for the induction of synaptic scaling at 1-2 dpl. Furthermore, laser capture microdissection combined with quantitative PCR demonstrates an increase in TNFα-mRNA levels in the denervated zone, which is consistent with our previous finding on a local, i.e., layer-specific increase in excitatory synaptic strength at 3-4 dpl. Immunostainings for the glial fibrillary acidic protein and TNFα suggest that astrocytes are a source of TNFα in our experimental setting. We conclude that TNFα-signaling is a major regulatory system that aims at maintaining the homeostatic synaptic response of denervated neurons.