Can you hear us now? The impact of health-care utilization by rare disease patients in the United States.

PURPOSE: The vast majority of rare diseases (RDs) are complex, disabling, and life-threatening conditions with a genetic origin. RD patients face significant health challenges and limited treatments, yet the extent of their impact within health care is not well known. One direct method to gauge the disease burden of RDs is their overall cost and utilization within health-care systems. METHODS: The 2016 Healthcare Cost and Utilization Project (HCUP) databases were used to extract health-care utilization data using International Classification of Diseases, Tenth Revision (ICD-10) codes. RESULTS: Of 35.6 million national hospital weighted discharges in the HCUP Nationwide Inpatient Sample, 32% corresponded to RD-associated ICD-10 codes. Total charges were nearly equal between RDs ($768 billion) compared to common conditions (CCs) ($880 billion) (p < 0.0001). These charges were a result of higher charges per discharge and longer length of stay (LOS) for RD patients compared to those with CCs (p < 0.0001). Health-care cost and utilization was similarly higher for RDs with pediatric inpatient stays, readmissions, and emergency visits. CONCLUSION: Pediatric and adult discharges with RDs show substantially higher health-care utilization compared to discharges with CCs diagnoses, accounting for nearly half of the US national bill.

Endogenous glutamatergic inputs to the Parabrachial Nucleus/Kölliker-Fuse Complex determine respiratory rate.

The Kölliker-Fuse Nucleus (KF) has been widely investigated for its contribution to "inspiratory off-switch" while more recent studies showed that activation of the Parabrachial Nucleus (PBN) shortened expiratory duration. This study used an adult, in vivo, decerebrate rabbit model to delineate the contribution of each site to inspiratory and expiratory duration through sequential block of glutamatergic excitation with the receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) and d(-)-2-amino-5-phosphonopentanoic acid (AP5). Glutamatergic disfacilitation caused large increases in inspiratory and expiratory duration and minor decrease in peak phrenic activity (PPA). Hypoxia only partially reversed respiratory rate depression but PPA was increased to >200 % of control. The contribution of PBN activity to inspiratory and expiratory duration was equal while block of the KF affected inspiratory duration more than expiratory. We conclude that in the in vivo preparation respiratory rate greatly depends on PBN/KF activity, which contributes to the "inspiratory on- "and "off-switch", but is of minor importance for the magnitude of phrenic motor output.

The contribution of endogenous glutamatergic input in the ventral respiratory column to respiratory rhythm.

Glutamate is the predominant excitatory neurotransmitter in the ventral respiratory column; however, the contribution of glutamatergic excitation in the individual subregions to respiratory rhythm generation has not been fully delineated. In an adult, in vivo, decerebrate rabbit model during conditions of mild hyperoxic hypercapnia we blocked glutamatergic excitation using the receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) and d(-)-2-amino-5-phosphonopentanoic acid (AP5). Disfacilitation of the preBötzinger Complex caused a decrease in inspiratory and expiratory duration as well as peak phrenic amplitude and ultimately apnea. Disfacilitation of the Bötzinger Complex caused a decrease in inspiratory and expiratory duration; subsequent disfacilitation of the preBötzinger Complex resulted in complete loss of the respiratory pattern but maintained tonic inspiratory activity. We conclude that glutamatergic drive to the preBötzinger Complex is essential for respiratory rhythm generation. Glutamatergic drive to the Bötzinger Complex significantly affects inspiratory and expiratory phase duration. Bötzinger Complex neurons are responsible for maintaining the silent expiratory phase of the phrenic neurogram.

Análisis de discapacidad utilizando WHODAS 2. 0 versión de 12 preguntas a pacientes de Instituto Teletón Santiago dos años después de su alta institucional / Analisis of disability using WHODAS 2. 0 among patients from Santiago Teleton Institute two years after discharge

Introducción: El Instituto Teletón Santiago es una organización sin fines de lucro dedicada a proporcionar rehabilitación integral a niños con discapacidades físicas hasta que cumplen 20 años de edad. Objetivo: Evaluar el nivel de discapacidad en sujetos del Instituto Teletón Santiago 2 años después del alta. Método: La versión de 12 ítems del cuestionario de Evaluación de la Discapacidad de la Organización Mundial de la Salud (12-Whodas) se aplicó a través de entrevista telefónica a pacientes o a su representante del Instituto Teletón Santiago 2 años después de su alta. Resultados: La puntuación mediana global de 12-Whodas fue de 17,0 puntos. La dificultad de desempeño es moderada o severa en todos los dominios en más del 40% de los pacientes y varía entre el 55,4% en movilidad y 42,6% en cuidado personal. El tener una actividad laboral independiente y educación universitaria fue asociado a una discapacidad leve (OR: 0,06 y 0,26, respectivamente), mientras que una mayor edad y el estar desempleados por razones de salud fue asociado a una discapacidad severa (OR: 1,15 y 2,80, respectivamen-te). Conclusiones: Hubo un nivel clínicamente significativo de discapacidad en todos los dominios descritos en 12-Whodas. Confirmamos los datos internacionales de que ser autónomo laboralmente y tener estudios universitarios está asociado con un menor nivel de discapacidad. Destaca la falta de educación inclusiva para estas personas. La adaptación y validación del instrumento 12-Whodas en individuos con enfermedades neuromusculo-esqueléticas es necesaria para proporcionar datos normativos específicos que permitan comparaciones internacionales.

Introduction: Chile Teletón Institute is a not-for-profit organization dedicated to providing comprehensive rehabilitation to children with physical disabilities until they reach 20 years of age. Method: The 12-item version of the World Health Organiza-tion Disability Assessment Schedule (12-Whodas) survey was applied by phone interview to patients or representatives from Santiago Teletón Institute, 2 years after discharge. Results: The 12-Whodas global median score was 17 points. The perfor-mance difficulty is moderate or severe in all domains in more than 40% of the patients, and varies between 55.4% in mobility and 42.6% in personal care. Being self-employed and having a college education were associated with a lower level of disabi-lity (OR: 0.06 and 0.26, respectively), whereas being older and unemployed for health reasons were associated with a higher likelihood of severe disability (OR: 1.15 and 2.80, respectively). Conclusions: There was a clinically significant level of disabi-lity in all the domains described in 12-Whodas. We confirm international data reporting that being self-employed and co-llege-educated are associated with a lower level of disability. A lack of inclusive education for this population stands out. Adaptation and validation of the 12-Whodas in individuals with neuromusculoskeletal disorders is needed to provide specific normative data allowing international comparisons.

Effectiveness of Oral Baclofen in the Treatment of Spasticity in Children and Adolescents With Cerebral Palsy.

OBJECTIVE: To systematically review the effectiveness of oral baclofen versus placebo or other antispastic oral medications in terms of body function, level of activity, and quality of life in children and adolescents with spastic cerebral palsy who are younger than 18 years. DATA SOURCES: Cochrane Library, Health Science Databases, DARE, LILACS, Embase, MEDLINE, OTseeker, PEDro, PsycINFO, SpeechBITE, ScienceDirect, Scopus, Trip, ClinicalTrials.gov, Google Scholar, OpenGrey, and manual search. STUDY SELECTION: Randomized or not randomized controlled trials and cohort studies comparing the effect of any dosage of oral baclofen with that of no treatment, placebo, or another antispastic medication in children and adolescents with spastic cerebral palsy were selected. DATA EXTRACTION: Following the Cochrane Handbook for Systematic Reviews of Interventions guidelines, 2 reviewers independently searched articles in databases from their inceptions until October 2014. DATA SYNTHESIS: Six randomized controlled trials involving a total of 130 patients were selected. Studies show a great variability in motor classification, dosage of baclofen, and outcome measures. There is conflicting evidence on the effectiveness of oral baclofen in reducing muscle tone or improving motor function or the level of activity. The overall methodological quality of the studies was low. The main qualitative limitations of the studies correspond to serious risk of bias, inconsistency of results, unpowered sample size, and publication bias. CONCLUSIONS: There are insufficient data to support or refute the use of oral baclofen for reducing spasticity or improving motor function in children and adolescents with spastic cerebral palsy.

Adenosine 2A receptor inhibition enhances intermittent hypoxia-induced diaphragm but not intercostal long-term facilitation.

Acute intermittent hypoxia (AIH) elicits diaphragm (Dia) and second external intercostal (T2 EIC) long-term facilitation (LTF) in normal unanesthetized rats. Although AIH-induced phrenic LTF is serotonin dependent, adenosine constrained in anesthetized rats, this has not been tested in unanesthetized animals. Cervical (C2) spinal hemisection (C2HS) abolishes phrenic LTF because of loss of serotonergic inputs 2 weeks post-injury, but LTF returns 8 weeks post-injury. We tested three hypotheses in unanesthetized rats: (1) systemic adenosine 2aA (A2A) receptor inhibition with intraperitoneal (IP) KW6002 enhances Dia and T2 EIC LTF in normal rats; (2) Dia and T2 EIC LTF are expressed after chronic (8 weeks), but not acute (1 week) C2HS; and (3) KW6002 enhances Dia and T2 EIC LTF after chronic (not acute) C2HS. Electromyography radiotelemetry was used to record Dia and T2 EIC activity during normoxia (21% O2), before and after AIH (10, 5-min 10.5% O2, 5-min intervals). In normal rats, KW6002 enhanced DiaLTF versus AIH alone (33.1±4.6% vs. 22.1±6.4% baseline, respectively; p<0.001), but had no effect on T2 EIC LTF (p>0.05). Although Dia and T2 EIC LTF were not observed 2 weeks post-C2HS, LTF was observed in contralateral (uninjured) Dia and T2 EIC 8 weeks post-C2HS (18.7±2.7% and 34.9±4.9% baseline, respectively; p<0.05), with variable ipsilateral expression. KW6002 had no significant effects on contralateral Dia (p=0.447) or T2 EIC LTF (p=0.796). We conclude that moderate AIH induces Dia and T2 EIC LTF after chronic, but not acute cervical spinal injuries. A single A2A receptor antagonist dose enhances AIH-induced Dia LTF in normal rats, but this effect is not significant in chronic (8 weeks) C2HS unanesthetized rats.