Using the BODE Index and Comorbidities to Predict Health Utilization Resources in Chronic Obstructive Pulmonary Disease.

Background and Objective: Chronic Obstructive Pulmonary Disease (COPD) is a common chronic respiratory disease that in the long term may develop into respiratory failure or even cause death and may coexist with other diseases. Over time, it may incur huge medical expenses, resulting in a heavy socio-economy burden. The BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index is a predictor of the number and severity of acute exacerbations of COPD. This study focused on the correlation between the BODE index, comorbidity, and healthcare resource utilization in COPD. Patients and Methods: This is a retrospective study of clinical outcomes of COPD patients with complete BODE index data in our hospital from January 2015 to December 2016. Based on the patients' medical records in our hospital's electronic database from January 1, 2015 to August 31, 2017, we analyzed the correlation between BODE index, Charlson comorbidity index (CCI), and medical resources. Results: Of the 396 patients with COPD who met the inclusion criteria, 382 (96.5%) were male, with an average age of 71.3 ± 8.4 years. Healthcare resource utilization was positively correlated with the BODE index during the 32 months of retrospective clinical outcomes. The study found a significant association between the BODE index and the CCI of COPD patients (p < 0.001). In-hospitalization expenses were positively correlated with CCI (p < 0.001). Under the same CCI, the higher the quartile, the higher the hospitalization expenses. BODE quartiles were positively correlated with number of hospitalizations (p < 0.001), hospitalization days (p < 0.001), hospitalization expenses (p = 0.005), and total medical expenses (p = 0.024). Conclusion: This study demonstrates the value of examining the BODE index and comorbidities that can predict healthcare resource utilization in COPD.

Wwox deficiency leads to neurodevelopmental and degenerative neuropathies and glycogen synthase kinase 3ß-mediated epileptic seizure activity in mice.

Human WWOX gene resides in the chromosomal common fragile site FRA16D and encodes a tumor suppressor WW domain-containing oxidoreductase. Loss-of-function mutations in both alleles of WWOX gene lead to autosomal recessive abnormalities in pediatric patients from consanguineous families, including microcephaly, cerebellar ataxia with epilepsy, mental retardation, retinal degeneration, developmental delay and early death. Here, we report that targeted disruption of Wwox gene in mice causes neurodevelopmental disorders, encompassing abnormal neuronal differentiation and migration in the brain. Cerebral malformations, such as microcephaly and incomplete separation of the hemispheres by a partial interhemispheric fissure, neuronal disorganization and heterotopia, and defective cerebellar midline fusion are observed in Wwox-/- mice. Degenerative alterations including severe hypomyelination in the central nervous system, optic nerve atrophy, Purkinje cell loss and granular cell apoptosis in the cerebellum, and peripheral nerve demyelination due to Schwann cell apoptosis correspond to reduced amplitudes and a latency prolongation of transcranial motor evoked potentials, motor deficits and gait ataxia in Wwox-/- mice. Wwox gene ablation leads to the occurrence of spontaneous epilepsy and increased susceptibility to pilocarpine- and pentylenetetrazol (PTZ)-induced seizures in preweaning mice. We determined that a significantly increased activation of glycogen synthase kinase 3ß (GSK3ß) occurs in Wwox-/- mouse cerebral cortex, hippocampus and cerebellum. Inhibition of GSK3ß by lithium ion significantly abolishes the onset of PTZ-induced seizure in Wwox-/- mice. Together, our findings reveal that the neurodevelopmental and neurodegenerative deficits in Wwox knockout mice strikingly recapitulate the key features of human neuropathies, and that targeting GSK3ß with lithium ion ameliorates epilepsy.