IMPORTANCE A strategy using mechanical chest compressions might improve the poor outcome in out-of-hospital cardiac arrest, but such a strategy has not been tested in large clinical trials.OBJECTIVE To determine whether administering mechanical chest compressions with defibrillation during ongoing compressions (mechanical CPR), compared with manual cardiopulmonary resuscitation (manual CPR), according to guidelines, would improve 4-hour survival. DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized clinical trial of 2589 patients with out-of-hospital cardiac arrest conducted between January 2008 and February 2013 in 4 Swedish, 1 British, and 1 Dutch ambulance services and their referring hospitals. Duration of follow-up was 6 months. INTERVENTIONS Patients were randomized to receive either mechanical chest compressions (LUCAS Chest Compression System, Physio-Control/Jolife AB) combined with defibrillation during ongoing compressions (n = 1300) or to manual CPR according to guidelines (n = 1289). MAIN OUTCOMES AND MEASURESFour-hour survival, with secondary end points of survival up to 6 months with good neurological outcome using the Cerebral Performance Category (CPC) score. A CPC score of 1 or 2 was classified as a good outcome.RESULTS Four-hour survival was achieved in 307 patients (23.6%) with mechanical CPR and 305 (23.7%) with manual CPR (risk difference, -0.05%; 95% CI, -3.3% to 3.2%; P > .99). Survival with a CPC score of 1 or 2 occurred in 98 (7.5%) vs 82 (6.4%) (risk difference, 1.18%; 95% CI, -0.78% to 3.1%) at intensive care unit discharge, in 108 (8.3%) vs 100 (7.8%) (risk difference, 0.55%; 95% CI, -1.5% to 2.6%) at hospital discharge, in 105 (8.1%) vs 94 (7.3%) (risk difference, 0.78%; 95% CI, -1.3% to 2.8%) at 1 month, and in 110 (8.5%) vs 98 (7.6%) (risk difference, 0.86%; 95% CI, -1.2% to 3.0%) at 6 months with mechanical CPR and manual CPR, respectively. Among patients surviving at 6 months, 99% in the mechanical CPR group and 94% in the manual CPR group had CPC scores of 1 or 2.CONCLUSIONS AND RELEVANCE Among adults with out-of-hospital cardiac arrest, there was no significant difference in 4-hour survival between patients treated with the mechanical CPR algorithm or those treated with guideline-adherent manual CPR. The vast majority of survivors in both groups had good neurological outcomes by 6 months. In clinical practice, mechanical CPR using the presented algorithm did not result in improved effectiveness compared with manual CPR.

This prospective study shows that the overall incidence of non-cardiac pain after sternotomy for cardiac surgery is high (28%). Most patients experience a modest pain intensity but some (1%) report severe pain, never being lower than 54 mm on VAS. The study also indicates that the incidence of pain after sternotomy is not only associated with harvest of the ITA and additional aetiological factors must be sought.

Ketamine showed a significant analgesic effect. The clinical usefulness is, however, limited by disturbing side-effects.

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Ketamine but not lidocaine showed a significant analgesic effect in patients with neuropathic pain after spinal cord injury. The pain relief was not associated with altered temperature thresholds or other changes of sensory function.

Aim To evaluate the analgesic efficacy of AZD1940, a novel peripherally acting cannabinoid CB1/CB2 receptor agonist, in patients undergoing third molar surgical removal. Methods This was a randomized, double-blind, placebo-controlled study in patients scheduled for surgical removal of an impacted lower third molar. Patients received a single oral dose of 800 μg AZD1940, 500 mg naproxen or placebo 1.5 h before surgery. The dose of 800 μg AZD1940 was selected based on earlier data from a single dose study in man, in which it was identified as the highest well tolerated dose. Ongoing post-operative pain (primary variable) and pain on jaw movement were assessed on a visual analog scale (VAS, 0-100 mm) from 0 to 8h postoperatively, deriving the area under the curve of ongoing pain (VAS AUC0-8h), and of pain on jaw movement (VASJM AUC0-8h). The time to requesting rescue medication (acetaminophen) was recorded. Subjective cannabinoid effects were assessed by the visual analog mood scale (VAMS). Results In total, 151 patients were randomized to AZD1940 (n = 61), placebo (n = 59) or naproxen (n = 31). There was no statistically significant difference in pain VAS AUC0-8h or in VASJM AUC0-8h between AZD1940 and placebo. Naproxen significantly reduced both pain VAS AUC0-8h and VASJM AUC0-8h as compared with placebo (p < 0.0001 for both). Significantly fewer patients on naproxen requested rescue medication and the duration of time to rescue was greater, as compared with placebo, whereas there were no significant differences between AZD1940 and placebo in these outcome variables. Statistically significant increases in VAMS items "sedated" and "high" were observed after AZD1940 compared with placebo. The increases in VAMS were numerically small compared with previous findings with a centrally acting cannabinoid. The most commonly observed adverse events (AE) on treatment with AZD1940 were postural dizziness (80% of subjects), nausea (26%), hypotension (21%) and headache (13%), most AE being mild to moderate. Conclusion The CB1/CB2 receptor agonist AZD1940 did not reduce post-operative pain after lower third molar surgical removal at doses exerting subjective cannabinoid effects. Implications Activation of peripheral CB1/CB2 receptors per se is probably of less clinical relevance for the treatment of acute nociceptive pain in man.

Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)-ketamine were measured in a randomized, double-blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes. Specific binding in the brain was assessed by simultaneous administration of (S)-[N-methyl-11C]ketamine quantified by positron emission tomography. High radioactivities in the brain corresponded to regional distribution of N-methyl-D-aspartate receptor complexes. A significant and dose-dependent reduction of binding was measured as a result of displacement of (S)-[N-methyl-11C]ketamine. Memory impairment and psychotomimetic effects were related to dose, plasma concentration 4 minutes after administration, and decreased regional binding of (S)-ketamine in the brain and were consistently seen at plasma and maximum regional brain (S)-ketamine concentrations higher than 70 and 500 ng/ml, respectively. The magnitude of specific binding of (S)-ketamine, measured with positron emission tomography, can be related directly to drug effects.

Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, plasma, and synovial fluid IL-6 (p-IL-6, sf-IL-6) were measured in 104 end-stage knee OA patients. Contrast-enhanced magnetic resonance imaging was used to semiquantitatively assess an 11-point synovitis score; pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Neuropathic Pain Questionnaire (NPQ). Linear regression was used to investigate associations between biomarkers and synovitis, and biomarkers and pain while controlling for age, sex, and body mass index. We also tested whether associations between biomarkers and pain were confounded by synovitis. We found sf-IL-6 was associated with synovitis in the parapatellar subregion (B = 0.006; 95% confidence interval [CI] 0.003-0.010), and no association between p-IL-6 and synovitis. We also observed an association between C1M and synovitis in the periligamentous subregion (B = 0.013; 95% CI 0.003-0.023). Furthermore, sf-IL-6, but not p-IL-6, was significantly associated with pain, WOMAC (B = 0.022; 95% CI 0.004-0.040), and NPQ (B = 0.043; 95% CI 0.005-0.082). There was no association between C1M and WOMAC pain, but we did find an association between C1M and NPQ (B = 0.229; 95% CI 0.036-0.422). Lastly, synovitis explained both biomarker-NPQ associations, but not the biomarker-WOMAC association. These results suggest that C1M and IL-6 are associated with synovitis and pain, and synovitis is an important confounding variable when studying biomarkers and neuropathic features in OA patients.