Performance of an eHealth (NOMHAD) System Comprising Telemonitoring, Telenotification, and Telecoaching for Patients With Multimorbidity: Proof-of-Concept Study.

BACKGROUND: Management of patients with multiple chronic diseases is a growing public health challenge, especially in rural sectors where access to physicians may be limited. Connected medical devices monitoring vital signs, associated with eHealth program and structured telephone support, may improve complex patient management through early detection of disease complications, positive impact on patients' health, and health resources consumption optimization. OBJECTIVE: The aim of this study was to evaluate the technical performance and user experience of the NOMHAD eHealth system in patients with multimorbidity. METHODS: This was a pilot, single-arm, interventional study. Patients with multimorbidity with any combination of chronic heart failure (CHF), chronic obstructive pulmonary disease, and diabetes were followed for 80-100 days using the NOMHAD eHealth system. This system used connected devices telemonitoring symptoms and vital signs (eg, body weight, oxygen saturation, pulse rate, blood pressure, and blood glucose), associated with structured telecoaching and educational support by call center nurses. An overall risk indicator (ORI) was automatically computed after each data teletransmission. The ORI was color coded; green indicated no action required; yellow, orange, and red (low to high priority, respectively) generated telenotifications and indicated to the nurses the need for a telecoaching action. Each ORI was calculated by combining 7 clinical stability system indicators based on symptom questionnaires and vital signs. Technical accuracy of the system was assessed by comparing system-generated ORIs with ORIs recalculated from raw data. Ease of use, usefulness, satisfaction, and acceptability of the system were assessed through patient adherence to self-assessments, and through self-administered questionnaires to patients, call center nurses, and physicians. RESULTS: A total of 23 patients were enrolled in this study and participated between April 2016 and March 2017 at 5 study centers in France. All patients were successfully equipped and evaluable for analysis. Mean age was 68.5 (SD 10.4) years and most patients were men (n=20). The most common multimorbidity was CHF + diabetes (n=15), followed by patients with all 3 diseases (n=5). Mean effective follow-up was 78.7 (SD 24.2) days. The system generated 6263 ORIs, as several ORIs could be generated on a single day for any patient. Overall system sensitivity was 99.2% (95% CI 98.9-99.4) and overall specificity was 91.3% (95% CI 87.7-94.1). Most patients (20/23, 87%) were satisfied with the system and agreed that it helped them to better understand and manage their diseases, and 19/23 (83%) valued the nurse regular contacts. Nurses and physicians were generally satisfied with the system and considered it useful. All users indicated they would agree to long-term use of the system. CONCLUSIONS: This study provides evidence that the NOMHAD eHealth system is accurate, acceptable, informative, and feasible for patients with multimorbidity, supporting further investigation of its clinical benefits. TRIAL REGISTRATION: Agence Nationale de Sécurité du Médicament et des Produits de Santé 2015-A01106-43; https://ictaxercb.ansm.sante.fr/Public/index.php.

Argon Attenuates Multiorgan Failure in Relation with HMGB1 Inhibition.

Argon inhalation attenuates multiorgan failure (MOF) after experimental ischemic injury. We hypothesized that this protection could involve decreased High Mobility Group Box 1 (HMGB1) systemic release. We investigated this issue in an animal model of MOF induced by aortic cross-clamping. Anesthetized rabbits were submitted to supra-coeliac aortic cross-clamping for 30 min, followed by 300 min of reperfusion. They were randomly divided into three groups (n = 7/group). The Control group inhaled nitrogen (70%) and oxygen (30%). The Argon group was exposed to a mixture of argon (70%) and oxygen (30%). The last group inhaled nitrogen/oxygen (70/30%) with an administration of the HMGB1 inhibitor glycyrrhizin (4 mg/kg i.v.) 5 min before aortic unclamping. At the end of follow-up, cardiac output was significantly higher in Argon and Glycyrrhizin vs. Control (60 ± 4 and 49 ± 4 vs. 33 ± 8 mL/kg/min, respectively). Metabolic acidosis was attenuated in Argon and Glycyrrhizin vs. Control, along with reduced amount of norepinephrine to reverse arterial hypotension. This was associated with reduced interleukin-6 and HMGB1 plasma concentration in Argon and Glycyrrhizin vs. Control. End-organ damages were also attenuated in the liver and kidney in Argon and Glycyrrhizin vs. Control, respectively. Argon inhalation reduced HMGB1 blood level after experimental aortic cross-clamping and provided similar benefits to direct HMGB1 inhibition.

A new mechanistic approach for the treatment of chronic neuropathic pain with nitrous oxide integrated from a systems biology narrative review.

The limitations of the currently available treatments for chronic neuropathic pain highlight the need for safer and more effective alternatives. The authors carried out a focused review using a systems biology approach to integrate the complex mechanisms of nociception and neuropathic pain, and to decipher the effects of nitrous oxide (N2O) on those pathways, beyond the known effect of N2O on N-methyl-D-aspartate receptors. This review identified a number of potential mechanisms by which N2O could impact the processes involved in peripheral and central sensitization. In the ascending pathway, the effects of N2O include activating TWIK-related K+ channel 1 potassium channels on first-order neurons, blocking voltage-dependent calcium channels to attenuate neuronal excitability, attenuating postsynaptic glutamatergic receptor activation, and possibly blocking voltage-dependent sodium channels. In the descending pathway, N2O induces the release of endogenous opioid ligands and stimulates norepinephrine release. In addition, N2O may mediate epigenetic changes by inhibiting methionine synthase, a key enzyme involved in DNA and RNA methylation. This could explain why this short-acting analgesic has shown long-lasting anti-pain sensitization effects in animal models of chronic pain. These new hypotheses support the rationale for investigating N2O, either alone or in combination with other analgesics, for the management of chronic neuropathic pain.

Modelling levels of nitrous oxide exposure for healthcare professionals during EMONO usage.

BACKGROUND: Computational fluid dynamics (CFD) has been used to compute nitrous oxide (N2O) levels within a room during the administration of an equimolar mix of N2O/oxygen (EMONO) in the clinical setting. This study modelled realistic scenarios of EMONO usage in hospital or primary care, in order to estimate the potential N2O exposure of healthcare professionals (HCP) with routine EMONO use and to provide guidance for EMONO users. METHODS: Sixteen scenarios were defined by carrying out a survey of practitioners. CFD simulations were performed for each scenario and N2O concentrations over time were calculated. N2O exposures (time-weighted average of concentration over 8 h [TWA-8 h]) were calculated at the HCPs' mouth to be compared with a predefined occupational exposure limit (OEL). RESULTS: Administration duration and ventilation type were the main factors influencing N2O levels; ventilation type also influenced wash-out time between EMONO administrations. N2O concentration showed a plume distribution towards the ceiling and was highly heterogeneous, highlighting the importance of measurement location. Although estimated TWA-8 h varied widely, 13 of the 16 scenarios had an N2O TWA-8 h of <100 parts per million. CONCLUSIONS: Data demonstrate that EMONO usage in well ventilated rooms - as recommended - helps to ensure that N2O exposure does not exceed the OEL and does not signal any major risks for HCPs when recommendations are followed. Although these data are numerical simulations and should be considered as such, they can provide guidance for EMONO users.

Equimolar nitrous oxide/oxygen versus placebo for procedural pain in children: a randomized trial.

OBJECTIVE: This randomized, single-dose, double-blind, Phase III study was designed to compare the level of procedural pain after use of premixed equimolar mixture of 50% oxygen and nitrous oxide (EMONO) or placebo (premixed 50% nitrogen and oxygen). METHODS: Patients aged 1 to 18 years were randomly assigned to receive EMONO (n = 52) or placebo (n = 48) delivered by inhalation through a facial mask 3 minutes before cutaneous, muscle, or bone/joint procedures. Pain was evaluated (on a scale from 0-10) using a self-reported Faces Pain Scale-Revised (FPS-R) or a Spanish observational pain scale (LLANTO). Rescue analgesia (with propofol or sevoflurane) was administered if pain scores were greater than or equal to 8. Collaboration, acceptance, ease of use and safety were evaluated by the attending nurse. RESULTS: There were significant differences between the 2 groups (EMONO versus placebo) for both scales (mean values): LLANTO: 3.5 vs 6.7, respectively (P = .01) and FPS-R: 3.2 vs 6.6, respectively (P = .0003). Patients not receiving EMONO (P = .0208)-in particular those aged younger than 3 years (P < .0001)-required more rescue analgesia. There were also significant differences between the 2 groups (EMONO versus placebo) for adequate collaboration (80% vs 35%; P < .0001) and acceptance (73% vs 25%; P < .0001). Ease of use was not significantly different between groups (98.1% vs 95.8%; P > .05). Only 2 patients (in the EMONO group) presented with mild adverse events. CONCLUSIONS: EMONO inhalation was well tolerated and had an estimated analgesic potency of 50%, and it is therefore suitable for minor pediatric procedures.