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Purpose To investigate the impact of etomidate on the rate of hospital-acquired pneumonia (HAP) in trauma patients and the effects of hydrocortisone in etomidate-treated patients. Methods This was a sub-study of the HYPOLYTE multi-centre, randomized, double-blind, placebo-controlled trial of hydrocortisone in trauma patients (NCT00563303). Inclusion criterion was trauma patient with mechanical ventilation (MV) of ≥48 h. The use of etomidate was prospectively collected. Endpoints were the results of the cosyntropin test and rate of HAP on day 28 of follow-up. Results Of the 149 patients enrolled in the study, 95 (64 %) received etomidate within 36 h prior to inclusion. 79 (83 %) of 95 patients receiving etomidate and 34 of the 54 (63 %) not receiving etomidate had corticosteroid insufficiency ( p  = 0.006). The administration of etomidate did not alter basal cortisolemia ( p  = 0.73), but it did decrease the delta of cortisolemia at 60 min ( p  = 0.007). There was a correlation between time from etomidate injection to inclusion in the study and sensitivity to corticotropin ( R 2  = 0.19; p  = 0.001). Forty-nine (51.6 %) patients with etomidate and 16 (29.6 %) patients without etomidate developed HAP by day 28 ( p  = 0.009). Etomidate was associated with HAP on day 28 in the multivariate analysis (hazard ratio 2.48; 95 % confidence interval 1.19–5.18; p  = 0.016). Duration of MV with or without etomidate was not significantly different ( p  = 0.278). Among etomidate-exposed patients, 18 (40 %) treated with hydrocortisone developed HAP compared with 31 (62 %) treated with placebo ( p  = 0.032). Etomidate-exposed patients treated with hydrocortisone had fewer ventilator days ( p  < 0.001). Conclusions Among the patients enrolled in the study, etomidate did not alter basal cortisolemia, but it did decrease reactivity to corticotropin. We suggest that in trauma patients, etomidate is an independent risk factor for HAP and that the administration of hydrocortisone should be considered after etomidate use.

Purpose Bupivacaine-induced myotoxicity is associated with mitochondrial bioenergetic alterations. The impact of the duration of bupivacaine treatment on mitochondrial energy production remains undetermined. Here, we assessed, in vivo , the alteration of mitochondrial metabolism following different durations of bupivacaine exposure (40, 56, or 112 hr) that correspond to 5, 7, or 14 repeated injections of 0.25% bupivacaine, respectively. Methods Rats were divided randomly into seven different groups: one control group (no catheter); three groups with normal saline injections (1 mL·kg −1 ) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr, respectively; and three groups with 0.25% bupivacaine injections (1 mL·kg −1 ) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr. Psoas and gracilis muscle samples located within the bupivacaine infusion-diffusion space were investigated. To estimate mitochondrial respiratory capacity, the protein content of the mitochondrial respiratory chain apparatus was evaluated by measuring citrate synthase activity. To measure mitochondrial respiratory function, adenosine diphosphate-stimulated oxygen consumption was measured by polarography in saponin-skinned muscle fibres using glutamate-malate or succinate as energy substrates. Results In psoas and gracilis muscles, saline solution had no effect on the two mitochondrial parameters. Bupivacaine induced a significant decrease in the citrate synthase activity in psoas (r 2  = 0.74; P  < 0.001) and gracilis muscle (r 2  = 0.52; P  < 0.001), and there was a significant decrease in the adenosine diphosphate-stimulated oxygen consumption using glutamate or succinate as substrates in both muscles ( P  < 0.001). Conclusions The severity of bupivacaine-induced myotoxicity is closely linked to the duration of bupivacaine exposure in the muscle fibres located close to the catheter tip.

Objective To assess the association between mind wandering (thinking unrelated to the task at hand) and the risk of being responsible for a motor vehicle crash. Design Responsibility case-control study. Setting Adult emergency department of a university hospital in France, April 2010 to August 2011. Participants 955 drivers injured in a motor vehicle crash. Main outcome measures Responsibility for the crash, mind wandering, external distraction, negative affect, alcohol use, psychotropic drug use, and sleep deprivation. Potential confounders were sociodemographic and crash characteristics. Results Intense mind wandering (highly disrupting/distracting content) was associated with responsibility for a traffic crash (17% (78 of 453 crashes in which the driver was thought to be responsible) v 9% (43 of 502 crashes in which the driver was not thought to be responsible); adjusted odds ratio 2.12, 95% confidence interval 1.37 to 3.28). Conclusions Mind wandering while driving, by decoupling attention from visual and auditory perceptions, can jeopardise the ability of the driver to incorporate information from the environment, thereby threatening safety on the roads.

The potential superiority of hypertonic saline (HTS) over mannitol (MTL) for control of intracranial pressure (ICP) following traumatic brain injury (TBI) is still debated. Forty-seven severe TBI patients with increased ICP were prospectively recruited in two university hospitals and randomly treated with equiosmolar infusions of either MTL 20% (4 mL/kg; n=25 patients) or HTS 7.5% (2 mL/kg; n=22 patients). Serum sodium, hematocrit, ICP, arterial blood pressure, cerebral perfusion pressure (CPP), shear rate, global indices of cerebral blood flow (CBF) and metabolism were measured before, and 30 and 120 min following each infusion during the course of illness. Outcome was assessed at 6 months. Both HTS and MTL effectively and equally reduced ICP levels with subsequent elevation of CPP and CBF, although this effect was significantly stronger and of longer duration after HTS and correlated with improved rheological blood properties induced by HTS. Further, effect of HTS on ICP appeared to be more robust in patients with diffuse brain injury. In contrast, oxygen and glucose metabolic rates were left equally unaffected by both solutions. Accordingly, there was no significant difference in neurological outcome between the two groups. In conclusion, MTL was as effective as HTS in decreasing ICP in TBI patients although both solutions failed to improved cerebral metabolism. HTS showed an additional and stronger effect on cerebral perfusion of potential benefit in the presence of cerebral ischemia. Treatment selection should therefore be individually based on sodium level and cerebral hemodynamics.

The purpose of this investigation was to determine the cause of death of a 13-year-old girl, where none was immediately evident. Our analysis showed it to be a very unusual case of a drug-facilitated sexual assault (DFSA), which led to the tragic death of the young rape victim and then to the suicide of the rapist. The incapacitating agent used was chloroform. The post-mortem analysis revealed a blood concentration of 833.9 mg/l for the girl, whereas the quantitation of chloroform in various fluids and viscera of the rapist proved that he had recently been handling the solvent (with concentrations in fat tissues 20 times higher than in his blood). This case draws attention to the need for broad searches for volatile substances in such investigations.

OBJECTIVE To assess the association between mind wandering (thinking unrelated to the task at hand) and the risk of being responsible for a motor vehicle crash. DESIGN Responsibility case-control study. SETTING Adult emergency department of a university hospital in France, April 2010 to August 2011. PARTICIPANTS 955 drivers injured in a motor vehicle crash. MAIN OUTCOME MEASURES Responsibility for the crash, mind wandering, external distraction, negative affect, alcohol use, psychotropic drug use, and sleep deprivation. Potential confounders were sociodemographic and crash characteristics. RESULTS Intense mind wandering (highly disrupting/distracting content) was associated with responsibility for a traffic crash (17% (78 of 453 crashes in which the driver was thought to be responsible) v 9% (43 of 502 crashes in which the driver was not thought to be responsible); adjusted odds ratio 2.12, 95% confidence interval 1.37 to 3.28). CONCLUSIONS Mind wandering while driving, by decoupling attention from visual and auditory perceptions, can jeopardise the ability of the driver to incorporate information from the environment, thereby threatening safety on the roads.

Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II–IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference −11·7, 95% CI −24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Alexion Pharmaceuticals.

Objective: Neuropsychological studies suggest that the ability to compensate for the presence of spatial neglect highly depends on the attentional resources a patient can rely on. The present research aimed to study neglect in situations where attentional resources are limited due to multitasking. Method: We examined two patients more than 3 years after a right-hemispheric stroke. Both had received neuropsychological rehabilitation for left neglect and did not show any impairment in standard tests. We used a dual-task paradigm combining a peripheral target detection task with a central shape recognition task. Peripheral targets could appear in left/right positions but also in lower/upper positions. Results: In patient #1, dual-task condition exacerbated left neglect and extinction. Patient #2 did not show any sign of neglect along the horizontal axis, but omitted half of the lower targets when they were presented simultaneously with upper targets under dual-task condition. This behavior reflects altitudinal extinction as the detection of single targets appearing either in upper or lower position was preserved. Conclusion: The present findings show that dual-tasking is a sensitive tool for the quantitative and qualitative assessment of spatial attention deficits, which are often overlooked by standard methods, especially in chronic stage. (JINS, 2019, 25, 644–653)