IntroductionAdalimumab, an anti-tumor necrosis factor antibody, is currently available in a 40 mg/0.8 mL formulation. The objective of this analysis was to evaluate injection site-related pain, safety, and tolerability of a 40 mg/0.4 mL formulation of adalimumab that had fewer excipients, a smaller volume, and a delivery presentation with a smaller gauge needle, versus the current 40 mg/0.8 mL formulation in patients with rheumatoid arthritis (RA).MethodsTwo identically designed, phase 2, randomized, single-blind, two-period crossover studies were conducted in Belgium and the Czech Republic (Study 1) and Australia, Canada, and Germany (Study 2). In both studies, adults with RA [biologic-naive or current users of 40 mg/0.8 mL adalimumab with an average injection site-related pain rating ≥3 cm on a visual analog scale (VAS; 0–10 cm)] were randomized to receive 40 mg/0.8 mL or 40 mg/0.4 mL adalimumab at visit 1. After 1–2 weeks (depending on patient medication schedule), patients received the other formulation at visit 2. A pain VAS [McGill Pain Questionnaire (MPQ-SF)] and the Draize scale were evaluated immediately after injection and 15 min postinjection. The primary endpoint was immediate pain after injection.Results64 and 61 patients were randomized in Studies 1 and 2, respectively. Both studies found a clinically relevant and statistically significant lower immediate pain after injection for the 40 mg/0.4 mL versus the 40 mg/0.8 mL formulation. The mean difference on the VAS for the pooled data (−2.48 cm) was also clinically relevant. Most other endpoints in both studies favored the 40 mg/0.4 mL formulation, and its tolerability and safety profile were consistent with 40 mg/0.8 mL adalimumab.ConclusionA 40 mg/0.4 mL adalimumab formulation was well tolerated and associated with less injection site-related pain than the 40 mg/0.8 mL adalimumab formulation.Trial registrationClinicalTrials.gov identifier, NCT01561313 and NCT01502423.FundingAbbVie.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-016-0041-3) contains supplementary material, which is available to authorized users.

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An enantioselective synthesis of the halogenated medium-ring ether natural product (+)-obtusenyne is reported which uses the ring expansion of a seven-membered ketene acetal by means of a Claisen rearrangement to construct the core nine-membered oxygen heterocycle. The trans substituents across the ether linkage were established by using a transition-metal-catalyzed intramolecular hydrosilation reaction of an exo-cyclic enol ether. In addition, a formal synthesis of ent-obtusenyne from 2-deoxy-D-ribose is reported. A number of interesting points regarding the chemistry of medium-ring oxygen heterocycles are highlighted.

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Purulent pericarditis is an extremely rare disease accounting for <1% of pericarditis cases. Purulent pericarditis with hemodyamically unstable tamponade if untreated is fatal. Furthermore, although idiopathic polymicrobial disease is documented, a combination Haemophilus parainfluenzae , Prevotella buccae , and Citrobacter freundii have not been found in the literature by the authors. What follows is a case of a 58‐year‐old male who presented to the emergency department (ED) with these features and underwent emergent bedside pericardiocentesis and a brief review of current pericardiocentesis techniques in the emergency department.

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A synthesis of the halogenated medium-ring ether natural product (+)-obtusenyne is reported utilizing a Claisen rearrangement and an intramolecular hydrosilation as key steps.