Pediatric care coordination and risk tiering: Moving beyond claims data.

PURPOSE: The goal of this study was to evaluate the performance of a pediatric stratification tool that incorporates health and non-medical determinants to identify children and youth with special health care needs (CYSHCN) patients according to increasing levels of complexity and compare this method to existing tools for pediatric populations. METHODS: This retrospective cohort study examined pediatric patients aged 0 to 21 years who received care at our institution between 2012 and 2015. We used the St. Luke's Children's Acuity Tool (SLCAT) to evaluate mean differences in dollars billed, number of encounters, and number of problems on the problem list and compared the SLCAT to the Pediatric Chronic Conditions Classification System version2 (CCCv2). RESULTS: Results indicate that the SLCAT assigned pediatric patients into levels reflective of resource utilization and found that children with highly complex chronic conditions had significantly higher utilization than those with mild and/or moderate complex conditions. The SLCAT found 515 patients not identified by the CCCv2. Nearly half of those patients had a mental/behavioral health diagnosis. CONCLUSIONS: The findings of this study provide evidence that a tiered classification model that incorporates all aspects of a child's care may result in more accurate identification of CYSHCN. This would allow for primary care provider and care coordination teams to match patients and families with the appropriate amount and type of care coordination services.

Effect of dexmedetomidine on sevoflurane-induced neurodegeneration in neonatal rats.

BACKGROUND: Structural brain abnormalities in newborn animals after prolonged exposure to all routinely used general anaesthetics have raised substantial concerns for similar effects occurring in millions of children undergoing surgeries annually. Combining a general anaesthetic with non-injurious sedatives may provide a safer anaesthetic technique. We tested dexmedetomidine as a mitigating therapy in a sevoflurane dose-sparing approach. METHODS: Neonatal rats were randomised to 6 h of sevoflurane 2.5%, sevoflurane 1% with or without three injections of dexmedetomidine every 2 h (resulting in 2.5, 5, 10, 25, 37.5, or 50 µg kg-1 h-1), or fasting in room air. Heart rate, oxygen saturation, level of hypnosis, and response to pain were measured during exposure. Neuronal cell death was quantified histologically after exposure. RESULTS: Sevoflurane at 2.5% was more injurious than at 1% in the hippocampal cornu ammonis (CA)1 and CA2/3 subfields; ventral posterior and lateral dorsal thalamic nuclei; prefrontal, retrosplenial, and somatosensory cortices; and subiculum. Although sevoflurane 1% did not provide complete anaesthesia, supplementation with dexmedetomidine dose dependently increased depth of anaesthesia and diminished responses to pain. The combination of sevoflurane 1% and dexmedetomidine did not reliably reduce neuronal apoptosis relative to an equianaesthetic dose of sevoflurane 2.5%. CONCLUSIONS: A sub-anaesthetic dose of sevoflurane combined with dexmedetomidine achieved a level of anaesthesia comparable with that of sevoflurane 2.5%. Similar levels of anaesthesia caused comparable programmed cell death in several developing brain regions. Depth of anaesthesia may be an important factor when comparing the neurotoxic effects of different anaesthetic regimens.

Clinical Care Coordination in Medically Complex Pediatric Cases: Results From the National Survey of Children With Special Health Care Needs.

This study uses a secondary analysis of the 2009-2010 National Survey of Children with Special Health Care Needs (NS-CSHCN) to describe care coordination (CC) for children with medical complexity (CMC). Chi-square test, t test, and multivariate logistic regression statistical tests are used to determine the relationships and differences between sources of CC and factors associated with receiving clinic-based CC for CMC and their family. Among CMC, 66.47% received no CC support and 25.73% received clinic-based CC. In multivariate models, families reporting dissatisfaction with communication between health care providers or reporting family-centered care were less likely to receive clinic-based CC. Families were more likely to receive clinic-based CC if they had younger children, lower household income, and greater school absenteeism. Clinic-based CC is associated with improved communication between health providers but must become more family-centered and minimize student absenteeism for the CMC population.

Long-term Fate Mapping to Assess the Impact of Postnatal Isoflurane Exposure on Hippocampal Progenitor Cell Productivity.

BACKGROUND: Exposure to isoflurane increases apoptosis among postnatally generated hippocampal dentate granule cells. These neurons play important roles in cognition and behavior, so their permanent loss could explain deficits after surgical procedures. METHODS: To determine whether developmental anesthesia exposure leads to persistent deficits in granule cell numbers, a genetic fate-mapping approach to label a cohort of postnatally generated granule cells in Gli1-CreER::GFP bitransgenic mice was utilized. Green fluorescent protein (GFP) expression was induced on postnatal day 7 (P7) to fate map progenitor cells, and mice were exposed to 6 h of 1.5% isoflurane or room air 2 weeks later (P21). Brain structure was assessed immediately after anesthesia exposure (n = 7 controls and 8 anesthesia-treated mice) or after a 60-day recovery (n = 8 controls and 8 anesthesia-treated mice). A final group of C57BL/6 mice was exposed to isoflurane at P21 and examined using neurogenesis and cell death markers after a 14-day recovery (n = 10 controls and 16 anesthesia-treated mice). RESULTS: Isoflurane significantly increased apoptosis immediately after exposure, leading to cell death among 11% of GFP-labeled cells. Sixty days after isoflurane exposure, the number of GFP-expressing granule cells in treated animals was indistinguishable from control animals. Rates of neurogenesis were equivalent among groups at both 2 weeks and 2 months after treatment. CONCLUSIONS: These findings suggest that the dentate gyrus can restore normal neuron numbers after a single, developmental exposure to isoflurane. The authors' results do not preclude the possibility that the affected population may exhibit more subtle structural or functional deficits. Nonetheless, the dentate appears to exhibit greater resiliency relative to nonneurogenic brain regions, which exhibit permanent neuron loss after isoflurane exposure.

Cell age-specific vulnerability of neurons to anesthetic toxicity.

OBJECTIVE: Anesthetics have been linked to widespread neuronal cell death in neonatal animals. Epidemiological human studies have associated early childhood anesthesia with long-term neurobehavioral abnormalities, raising substantial concerns that anesthetics may cause similar cell death in young children. However, key aspects of the phenomenon remain unclear, such as why certain neurons die, whereas immediately adjacent neurons are seemingly unaffected, and why the immature brain is exquisitely vulnerable, whereas the mature brain seems resistant. Elucidating these questions is critical for assessing the phenomenon's applicability to humans, defining the susceptible age, predicting vulnerable neuronal populations, and devising mitigating strategies. METHODS: This study examines the effects of anesthetic exposure on late- and adult-generated neurons in newborn, juvenile, and adult mice, and characterizes vulnerable cells using birth-dating and immunohistochemical techniques. RESULTS: We identify a critical period of cellular developmental during which neurons are susceptible to anesthesia-induced apoptosis. Importantly, we demonstrate that anesthetic neurotoxicity can extend into adulthood in brain regions with ongoing neurogenesis, such as dentate gyrus and olfactory bulb. INTERPRETATION: Our findings suggest that anesthetic vulnerability reflects the age of the neuron, not the age of the organism, and therefore may potentially not only be relevant to children but also to adults undergoing anesthesia. This observation further predicts differential heightened regional vulnerability to anesthetic neuroapoptosis to closely follow the distinct regional peaks in neurogenesis. This knowledge may help guide neurocognitive testing of specific neurological domains in humans following exposure to anesthesia, dependent on the individual's age during exposure.

Omega-3 fatty acid deficiency augments risperidone-induced hepatic steatosis in rats: positive association with stearoyl-CoA desaturase.

Psychiatric patients frequently exhibit long-chain n-3 (LCn-3) fatty acid deficits and elevated triglyceride (TAG) production following chronic exposure to second generation antipsychotics (SGAs). Emerging evidence suggests that SGAs and LCn-3 fatty acids have opposing effects on stearoyl-CoA desaturase-1 (SCD1), which plays a pivotal role in TAG biosynthesis. Here we evaluated whether low LCn-3 fatty acid status would augment elevations in rat liver and plasma TAG concentrations following chronic treatment with the SGA risperidone (RSP), and evaluated relationships with hepatic SCD1 expression and activity indices. In rats maintained on the n-3 fatty acid-fortified (control) diet, chronic RSP treatment significantly increased liver SCD1 mRNA and activity indices (18:1/18:0 and 16:1/16:0 ratios), and significantly increased liver, but not plasma, TAG concentrations. Rats maintained on the n-3 deficient diet exhibited significantly lower liver and erythrocyte LCn-3 fatty acid levels, and associated elevations in LCn-6/LCn-3 ratio. In n-3 deficient rats, RSP-induced elevations in liver SCD1 mRNA and activity indices (18:1/18:0 and 16:1/16:0 ratios) and liver and plasma TAG concentrations were significantly greater than those observed in RSP-treated controls. Plasma glucose levels were not altered by diet or RSP, and body weight was lower in RSP- and VEH-treated n-3 deficient rats. These preclinical data support the hypothesis that low n-3 fatty acid status exacerbates RSP-induced hepatic steatosis by augmenting SCD1 expression and activity.

Abnormalities of granule cell dendritic structure are a prominent feature of the intrahippocampal kainic acid model of epilepsy despite reduced postinjury neurogenesis.

PURPOSE: Aberrant plastic changes among adult-generated hippocampal dentate granule cells are hypothesized to contribute to the development of temporal lobe epilepsy. Changes include formation of basal dendrites projecting into the dentate hilus. Innervation of these processes by granule cell mossy fiber axons leads to the creation of recurrent excitatory circuits within the dentate. The destabilizing effect of these recurrent circuits may contribute to hyperexcitability and seizures. Although basal dendrites have been identified in status epilepticus models of epilepsy associated with increased neurogenesis, we do not know whether similar changes are present in the intrahippocampal kainic acid model of epilepsy, which is associated with reduced neurogenesis. METHODS: In the present study, we used Thy1-YFP-expressing transgenic mice to determine whether hippocampal dentate granule cells develop hilar-projecting basal dendrites in the intrahippocampal kainic acid model. Brain sections were examined 2 weeks after treatment. Tissue was also examined using ZnT-3 immunostaining for granule cell mossy fiber terminals to assess recurrent connectivity. Adult neurogenesis was assessed using the proliferative marker Ki-67 and the immature granule cell marker calretinin. KEY FINDINGS: Significant numbers of cells with basal dendrites were found in this model, but their structure was distinct from basal dendrites seen in other epilepsy models, often ending in complex tufts of short branches and spines. Even more unusual, a subset of cells with basal dendrites had an inverted appearance; they completely lacked apical dendrites. Spines on basal dendrites were found to be apposed to ZnT-3 immunoreactive puncta, suggestive of recurrent mossy fiber input. Finally, YFP-expressing abnormal granule cells did not colocalize Ki-67 or calretinin, indicating that these cells were more than a few weeks old, but were found almost exclusively in proximity to the neurogenic subgranular zone, where the youngest granule cells are located. SIGNIFICANCE: Recent studies have demonstrated in other models of epilepsy that dentate pathology develops following the aberrant integration of immature, adult-generated granule cells. Given these findings, one might predict that the intrahippocampal kainic acid model of epilepsy, which is associated with a dramatic reduction in adult neurogenesis, would not exhibit these changes. Herein we demonstrate that hilar basal dendrites are a common feature of this model, with the abnormal cells likely resulting from the disruption of juvenile granule cell born in the weeks before the insult. These studies demonstrate that postinjury neurogenesis is not required for the accumulation of large numbers of abnormal granule cells.

Omega-3 fatty acid deficiency increases stearoyl-CoA desaturase expression and activity indices in rat liver: positive association with non-fasting plasma triglyceride levels.

Although omega-3 (n-3) fatty acids negatively regulate triglyceride biosynthesis, the mechanisms mediating this effect are poorly understood, and emerging evidence suggests that stearoyl-CoA desaturase (Scd1) is required for de novo triglyceride biosynthesis. To investigate this mechanism, we determined the effects of perinatal n-3 deficiency and postnatal repletion on rat liver Scd1 mRNA expression and activity indices (liver 16:1/16:0 and 18:1/18:0 ratios), and determined relationships with postprandial (non-fasting) plasma triglyceride levels. Rats were fed conventional diets with or without the n-3 fatty acid precursor α-linolenic acid (ALA, 18:3n-3) during perinatal development (E0-P100), and a subset of rats fed the ALA- diet were switched to the ALA+ diet post-weaning (P21-P100, repletion). Compared with controls, rats fed the ALA- diet exhibited significantly lower liver long-chain n-3 fatty acid compositions and elevations in monounsaturated fatty acid composition, both of which were normalized in repleted rats. Liver Scd1 mRNA expression and activity indices (16:1/16:0 and 18:1/18:0 ratios) were significantly greater in n-3 deficient rats compared with controls and repleted rats. Among all rats, liver Scd1 mRNA expression was positively correlated with liver 18:1/18:0 and 16:1/16:0 ratios. Plasma triglyceride levels, but not glucose or insulin levels, were significantly greater in n-3 deficient rats compared with controls and repleted rats. Liver Scd1 mRNA expression and activity indices were positively correlated with plasma triglyceride levels. These preclinical findings demonstrate that n-3 fatty acid status is an important determinant of liver Scd1 mRNA expression and activity, and suggest that down-regulation of Scd1 is a mechanism by which n-3 fatty acids repress constitutive triglyceride biosynthesis.

Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids.

Olfactory perceptual stability and discrimination.

No two roses smell exactly alike, but our brain accurately bundles these variations into a single percept 'rose'. We found that ensembles of rat olfactory bulb neurons decorrelate complex mixtures that vary by as little as a single missing component, whereas olfactory (piriform) cortical neural ensembles perform pattern completion in response to an absent component, essentially filling in the missing information and allowing perceptual stability. This piriform cortical ensemble activity predicts olfactory perception.