Red Blood Cell Distribution Width is Associated with Poor Clinical Outcome After Subarachnoid Hemorrhage: A Pilot Study.

INTRODUCTION: The red cell distribution width (RDW) is a biomarker strongly associated with poor outcome in inflammatory and thrombotic diseases. Subarachnoid hemorrhage (SAH) is both an inflammatory and thrombotic state in which many biomarkers have been studied. In this exploratory pilot study, we sought to determine whether RDW predicts poor outcome in patients with SAH. METHODS: Patients with moderate-to-severe SAH were prospectively enrolled in an observational study of biomarkers and outcome. CBC, ESR, high sensitivity CRP, D-dimer, and fibrinogen were obtained on post-bleed days (PBD) 1, 3, 5, 7, and 10. Poor outcome was defined as a modified Rankin score of 3-6 at 90-days. RESULTS: Of 40 patients, 5 (12.5%) died and 19 (47.5%) had a poor outcome. RDW (p = 0.046) when measured serially over the study period, was significantly higher among patients with poor outcome. Maximum RDW (OR 2.3 95% CI 1.2-3.6; p = 0.014) and maximum WBC count (OR 1.29 95% CI 1.04-1.60; p = 0.018) were associated with poor outcome. Stepwise addition of maximum ESR, CRP, D-dimer, and fibrinogen yielded a model with RDW (OR 2.54 95% CI 1.21-5.35; p = 0.014) and fibrinogen (OR 1.01 95% CI 1.002-1.01; p = 0.004) predicting outcome. With addition of age and Hunt and Hess grade, RDW, fibrinogen, and high-grade status remained significantly associated with poor outcome. Use of PBD1 RDW in lieu of maximum RDW, resulted in a similar model. CONCLUSIONS: An elevated RDW is associated with poor outcome in SAH patients. RDW may be a useful predictor of outcomes after SAH.

The RAIS Device for Global Surgery: Using a Participatory Design Approach to Navigate the Translational Pathway to Clinical Use.

BACKGROUND: Over 5 billion people worldwide have no access to surgery worldwide, typically in low-resource settings, despite it being a primary life-saving treatment. Gas Insufflation-Less Laparoscopic Surgery (GILLS) can address this inequity, by improving current GILLS instrumentation to modern surgical standards. OBJECTIVE: to develop and translate a new Retractor for Abdominal Insufflation-less Surgery (RAIS) into clinical use and thus provide a context-appropriate system to advance GILLS surgery. METHODS: A collaborative multidisciplinary team from the UK and India was formed, embedding local clinical stakeholders and an industry partner in defining user and contextual needs. System development was based on a phased roadmap for 'surgical device design in low resource settings' and embedded participatory and frugal design principles in an iterative process supported by traditional medical device design methodologies. Each phase of development was evaluated by the stakeholder team through interactive workshops using cadaveric surgical simulations. A Commercialisation phase undertook Design to Manufacture and regulatory approval activities. Clinical validation was then conducted with rural surgeons performing GILLS procedures using the RAIS system. Semi-structured questionnaires and interviews were used to evaluate device performance. RESULTS: A set of user needs and contextual requirements were defined and formalised. System development occurred across five iterations. Stakeholder participation was instrumental in converging on a design which met user requirements. A commercial RAIS system was then produced by an industry partner under Indian regulatory approval. This was successfully used in clinical validation to conduct 12 surgical procedures at two locations in rural India. Surgical feedback showed that the RAIS system provided a valuable and usable surgical instrument which was appropriate for use in low-resource contexts. CONCLUSIONS: Using a context-specific development approach with close engagement of stakeholders was crucial to develop the RAIS system for low-resource regions. The outcome is translation from global health need into a fully realized commercial instrument which can be used by surgeons in low-resource regions across India.

Role of kappa- and delta-opioid receptors in the antinociceptive effect of oxytocin in formalin-induced pain response in mice.

Oxytocin has been implicated in the modulation of somatosensory transmission such as nociception and pain. The present study investigates the effect of oxytocin on formalin-induced pain response, a model of tonic continuous pain. The animals were injected with 0.1 ml of 1% formalin in the right hindpaw and the left hindpaw was injected with an equal volume of normal saline. The time spent by the animals licking or biting the injected paw during 0-5 min (early phase) and 20-25 min (late phase) was recorded separately. Oxytocin (25, 50, 100 microg/kg, i.p.) dose dependently decreased the licking/biting response, both in the early as well as the late phases. The antinociceptive effect of oxytocin (100 microg/kg, i.p.) was significantly attenuated in both the phases by a higher dose of the non-selective opioid receptor antagonist naloxone (5 mg/kg, i.p.), MR 2266 (0.1 mg/kg, i.p.), a selective kappa-opioid receptor antagonist and naltrindole (0.5 mg/kg, i.p.), a selective delta-opioid receptor antagonist but not by a lower dose of naloxone (1 mg/kg, i.p.) or beta-funaltrexamine (2.5 microg/mouse, i.c.v.), a selective mu-opioid receptor antagonist. Nimodipine, a calcium channel blocker (1 and 5 mg/kg, i.p.) produced a dose-dependent analgesic effect. The antinociceptive effect of oxytocin was significantly enhanced by the lower dose of nimodipine (1 mg/kg, i.p.) in both the phases. Chronic treatment with oxytocin (100 microg/kg/day, i.p. daily for 7 days) did not produce tolerance in both the phases of formalin-induced pain response. The results thus indicate that oxytocin displays an important analgesic response in formalin test; both kappa- and delta-opioid receptors as well as voltage-gated calcium channels seem to be involved in the oxytocin-induced antinociception.