Background Inadvertent intra‐arterial injection of dermal fillers including calcium hydroxylapatite (CaHA) can result in serious adverse events including soft tissue necrosis, permanent scarring, visual impairment, and blindness. When intra‐arterial injection occurs, immediate action is required for optimal outcomes, but the infrequency of this event means that many physicians may never have experienced this scenario. The aim of this document is to provide evidence‐based and expert opinion recommendations for the recognition and management of vascular compromise following inadvertent injection of CaHA. Methods An international group of experts with experience in injection of CaHA and management of vascular complications was convened to develop a consensus on the optimal management of vascular compromise following intra‐arterial CaHA injection. The consensus members were asked to provide preventative advice for the avoidance of intravascular injection and to produce a treatment protocol for acute and delayed presentation. To ensure all relevant treatment options were included, the recommendations were supplemented with a PubMed search of the literature. Results For prevention of intra‐arterial CaHA injection, consensus members outlined the importance of a thorough knowledge of facial vascular anatomy and patient history, as well as highlighting potential risk zones and optimal injection techniques. Individual sections document how to recognize the symptoms of vascular occlusion leading to vision loss and tissue necrosis as well as detailed treatment protocols for the management of these events. For impending tissue necrosis, recommendations are provided for early and delayed presentations with treatment protocols for acute and follow‐up treatment. A separate section details the treatment options for open and closed wounds. Conclusions All physicians should be prepared for the eventuality of intra‐arterial injection of a dermal filler, despite its rarity. These consensus recommendations combine advice from aesthetic experts with the latest reports from the published literature to provide an up‐to‐date office‐based protocol for the prevention and treatment of complications arising from intra‐arterial CaHA injection.

Background: This is the first report of the pharmacodynamic (PD) effects of the selective, potent and brain-penetrant P2X7 receptor (P2X7R) antagonist JNJ-54175446. Activation of the P2X7R, an adenosine triphosphate-gated ion channel, leads to the production of pro-inflammatory cytokines, which have been linked to neuroinflammation and play a role in the pathogenesis of mood disorders. Previous clinical studies with JNJ-54175446 demonstrated peripheral target engagement of JNJ-54175446 by assessing ex vivo lipopolysaccharide (LPS)-stimulated cytokine production. Blood–brain barrier penetration and a clear dose–receptor occupancy relationship was demonstrated using positron emission tomography. Aims: The objectives of this double-blind, placebo-controlled, translational study were to assess the safety and tolerability of administering multiple doses of JNJ-54175446 and to explore its PD effects using a dexamphetamine challenge. Methods: Subjects ( N = 64) were randomised to either JNJ-54175446 (50–450 mg; n = 48) or placebo ( n = 16) and underwent a baseline oral 20 mg dexamphetamine challenge followed by 11 consecutive days q.d. dosing with JNJ-54175446/placebo and a randomised crossover dexamphetamine/placebo challenge. Results: At all doses tested, JNJ-54175446 was well tolerated and suppressed the ex vivo LPS-induced release of cytokines. At doses ⩾100 mg, JNJ-54175446 attenuated dexamphetamine-induced increases in locomotion and enhanced the mood-elevating effects of dexamphetamine, suggesting that a dose that is approximately twice as high is needed to obtain a central PD response compared to the dose needed for maximum peripheral occupancy. Conclusion: Overall, the observed pharmacological profile of JNJ-54175446 in the dexamphetamine challenge paradigm is compatible with a potential mood-modulating effect.

Editor's key points † Postoperative nausea and vomiting (PONV) is one of the main adverse outcomes leading to delayed discharge. † A range of guidelines are available that may reduce PONV, but are often not implemented. † This study assesses the use of an automated reminder system to improve compliance with guidelines. † PONV was reduced by automated reminders, particularly in high-risk patients.Background. Guidelines to minimize the incidence of postoperative nausea and vomiting (PONV) have been implemented in many hospitals. In previous studies, we have demonstrated that guideline adherence is suboptimal and can be improved using decision support (DS). In this study, we investigate whether DS improves patient outcome through improving physician behaviour.Methods. Medical information of surgical patients is routinely entered in our anaesthesia information management system (AIMS), which includes automated reminders for PONV management based on the simplified risk score by Apfel and colleagues. This study included consecutive adult patients undergoing general anaesthesia for elective noncardiac surgery who were treated according to the normal clinical routine. The presence of PONV was recorded in the AIMS both during the recovery period and at 24 h. Two periods were studied: one without the use of DS (control period) and one with the use of DS (support period). DS consisted of reminders on PONV both in the preoperative screening clinic and at the time of anaesthesia.Results. In the control period, 981 patients, of whom 378 (29%) were high-risk patients, received general anaesthesia. Overall, 264 (27%) patients experienced PONV within 24 h. In the support period, 1681 patients, of whom 525 (32%) had a high risk for PONV, received general anaesthesia. In this period, only 378 (23%) patients experienced PONV within 24 h after operation. This difference is statistically significant (P¼0.01).Conclusion. Automated reminders can improve patient outcome by improving guideline adherence.

Sodium channel blockers are used for the treatment of pain, but this is limited by the lack of selectivity for different sodium channel subtypes, which can result in central nervous system and cardiovascular side effects. As such, there is special interest in the Nav1.7 subtype, which is expressed predominantly in nociceptive and sympathetic neurons. The aim was to demonstrate analgesic properties of a potent selective Nav1.7 sodium channel blocker, PF‐05089771, alone and concomitantly with pregabalin in healthy subjects using a battery of human evoked pain models. This was a double‐blind, double‐dummy, randomized, placebo‐controlled, five‐period cross‐over study with PF‐05089771 alone and PF‐05089771 concomitantly with pregabalin as treatment arms with pregabalin, ibuprofen, and placebo as control arms (NCT02349607). A battery of human evoked pain models was used to investigate analgesic properties of PF‐05089771. Twenty‐five subjects were enrolled in the study of which 23 subjects completed all five periods. PF‐05089771 alone did not differ from placebo on the primary pain end points. The same holds when comparing PF‐05089771 concomitantly with pregabalin and pregabalin alone. Pregabalin showed significant effects relative to placebo on thermal pain on the normal skin and UVB skin (least squares means with 90% confidence interval: 0.63 (0.32–0.93) and 0.53 (0.11–0.96)), pressure stimulation (1.10 (1.04–1.18)), and cold pressor (1.22 (1.14–1.32)). Ibuprofen demonstrated significant effects on thermal pain UVB skin (1.26 (0.82–1.70)) and pressure stimulation assessment (1.08 (1.01–1.15)), consistent with historical results. This study did not demonstrate analgesic properties of PF‐05089771 alone or concomitantly with pregabalin in a battery of pain models.

The multimodal battery of evoked pain tasks utilized in this study may play an important role in early-phase clinical drug development. This battery of pain tasks is not sensitive to the effects of sedation alone, and thus suitable to investigate the analgesic potential of novel analgesic compounds.