In this review, we provide an overview of the US Food and Drug Administration (FDA)-approved clinical uses of vagus nerve stimulation (VNS) as well as information about the ongoing studies and preclinical research to expand the use of VNS to additional applications. VNS is currently FDA approved for therapeutic use in patients aged >12 years with drug-resistant epilepsy and depression. Recent studies of VNS in in vivo systems have shown that it has anti-inflammatory properties which has led to more preclinical research aimed at expanding VNS treatment across a wider range of inflammatory disorders. Although the signaling pathway and mechanism by which VNS affects inflammation remain unknown, VNS has shown promising results in treating chronic inflammatory disorders such as sepsis, lung injury, rheumatoid arthritis (RA), and diabetes. It is also being used to control pain in fibromyalgia and migraines. This new preclinical research shows that VNS bears the promise of being applied to a wider range of therapeutic applications.

Context. Infants of age less than one year have the highest mortality rate in pediatrics. The American Academy of Pediatrics published guidelines for palliative care in 2013; however, significant variation persists among local protocols addressing neonatal comfort care at the end-of-life (EOL). Objectives. The purpose of this study was to evaluate current neonatal EOL comfort care practices and clinician satisfaction across America. Methods. After institutional review board approval (516005), an anonymous, electronic survey was sent to members of the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine. Members of the listserv include neonatologists, neonatal fellow physicians, neonatal nurses, and neonatal nurse practitioners from across America (U.S. and Canada). Results. There were 346/3000 (11.5%) responses with wide geographic distribution and high levels of intensive care responding (46.1% Level IV, 50.9% Level III, 3.0% Level II). Nearly half (45.2%) reported that their primary institution did not have neonatal comfort care guidelines. Of those reporting institutional neonatal comfort care guidelines, 19.1% do not address pain symptom management. Most guidelines also do not address gastrointestinal distress, anxiety, or secretions. Thirty-nine percent of respondents stated that their institution did not address physician compassion fatigue. Overall, 91.8% of respondents felt that their institution would benefit from further education/training in neonatal EOL care. Conclusion. Across America, respondents confirmed significant variation and verified many institutions do not formally address neonatal EOL comfort care. Institutions with guidelines commonly appear to lack crucial areas of palliative care including patient symptom management and provider compassion fatigue. The overwhelming majority of respondents felt that their institutions would benefit from further neonatal EOL care training.

No abstract

We are developing a series of thiolesters that produce an immediate and sustained reversal of the deleterious effects of opioids, such as morphine and fentanyl, on ventilation without diminishing the antinociceptive effects of these opioids. We report here the effects of systemic injections of L-cysteine methyl ester (L-CYSme) on morphine-induced changes in ventilatory parameters, arterial-blood gas (ABG) chemistry (pH, pCO2, pO2, sO2), Alveolar-arterial (A-a) gradient (i.e., the index of alveolar gas-exchange within the lungs), and antinociception in unanesthetized Sprague Dawley rats. The administration of morphine (10 mg/kg, IV) produced a series of deleterious effects on ventilatory parameters, including sustained decreases in tidal volume, minute ventilation, inspiratory drive and peak inspiratory flow that were accompanied by a sustained increase in end inspiratory pause. A single injection of L-CYSme (500 μmol/kg, IV) produced a rapid and long-lasting reversal of the deleterious effects of morphine on ventilatory parameters, and a second injection of L-CYSme (500 μmol/kg, IV) elicited pronounced increases in ventilatory parameters, such as minute ventilation, to values well above pre-morphine levels. L-CYSme (250 or 500 μmol/kg, IV) also produced an immediate and sustained reversal of the deleterious effects of morphine (10 mg/kg, IV) on arterial blood pH, pCO2, pO2, sO2 and A-a gradient, whereas L-cysteine (500 μmol/kg, IV) itself was inactive. L-CYSme (500 μmol/kg, IV) did not appear to modulate the sedative effects of morphine as measured by righting reflex times, but did diminish the duration, however, not the magnitude of the antinociceptive actions of morphine (5 or 10 mg/kg, IV) as determined in tail-flick latency and hindpaw-withdrawal latency assays. These findings provide evidence that L-CYSme can powerfully overcome the deleterious effects of morphine on breathing and gas-exchange in Sprague Dawley rats while not affecting the sedative or early stage antinociceptive effects of the opioid. The mechanisms by which L-CYSme interferes with the OR-induced signaling pathways that mediate the deleterious effects of morphine on ventilatory performance, and by which L-CYSme diminishes the late stage antinociceptive action of morphine remain to be determined.

Modern hospitals are equipped with sophisticated monitoring equipment that displays enormous volumes of raw data about the cardiopulmonary and neural functions of patients. The latest generation of bedside monitors attempts to present these data to the clinician in an integrated fashion to better represent the overall physiological condition of the patient. However, none of these systems are capable of extracting potentially important indices of pattern variability inherent within biological signals. This review has three main objectives. (1) To summarize the current state of data acquisition in the intensive care unit and identify limitations that must be overcome to achieve the goal of real-time processing of biological signals to capture subtleties identifying "early warning signals" hidden in physiologic patterns that may reflect current severity of the disease process and, more importantly, predict the likelihood of adverse progression and death or improvement and resolution. (2) To outline our approach to analyzing biological waveform data based on work in animal models of human disease. (3) To propose guidelines for the development, testing and implementation of integrated software and hardware solutions that will facilitate the novel application of complex systems approaches to biological waveform data with the goal of risk assessment.