kill' strategy, for future trials significant enhancement of both 'kick' and 'kill' agents will be required. Research in context panel Evidence before this study This randomised clinical trial was designed to test the concept of 'kick and kill' as a strategy to achieve a cure for HIV infection. Prior to this study, there was evidence from in vitro and single arm clinical studies that the histone deacetylase inhibitor (HDACi) class of drugs could induce viral transcription from latently infected cells, potentially creating a target for the immune system. In conjunction with this 'kick' to the latent HIV reservoir there was evidence that T cell immunitywhich determines HIV disease progression-could be enhanced through vaccination-induced responses, providing the 'kill'. Although the strategy of 'kick and kill' looked promising, there had been no powered RCTs to test it. Added value of the study RIVER tested 'kick and kill' using the HDACi vorinostat as the 'kick' combined with a vaccine strategy targeting conserved regions of the HIV genome. The vaccine aimed to produce T cells to kill latently-infected cells in which viral transcription had been induced by the HDACi. RIVER showed that the intervention was safe, with outstanding adherence to the complex trial protocol by the participants. However, even though there was evidence for both increased histone acetylation and potent vaccine-induced T-cell responses, the intervention did not confer any additional benefit on any measures of the HIV reservoir compared with antiretroviral therapy alone. Implications of all the available evidence. RIVER was the first RCT in treated recent HIV infection, and was not able to show any impact of 'kick and kill' on the primary outcome measure, or any marker of the HIV reservoir size. This is consistent with other studies which had tested HDACi alone. We did not, however, stop antiretroviral therapy in the RIVER trial participants, and future studies may include a treatment interruption as a further measure of impact. Whilst the RIVER trial suggests that this specific 'kick and kill' approach may not be an effective approach towards achieving HIV cure, the overall principle can not yet be dismissed, as more potent future interventions may have a greater impact.

No abstract

Twenty-five horses undergoing arthroscopic surgery were studied to develop a scheme for assessing pain in horses while investigating the effects of phenylbutazone (PBZ) analgesia. Fifteen of the 25 horses received PBZ 4 mg/kg intravenously (IV) before surgery and 2 mg/kg (IV) every 12 hours thereafter until 60 hours; the remaining 10 (placebo group) were given a corresponding volume of saline. In both groups, venous blood samples were collected for catecholamine, beta-endorphin, and cortisol assays before premedication and up to 72 hours after surgery. Postoperative pain was evaluated by measuring predefined behavioral and physiological variables. A total postoperative pain severity index (TPPSI) was calculated using all variables. There were no differences between PBZ and placebo groups in plasma beta-endorphin or catecholamine concentrations, but the TPPSI was higher in the placebo group than in the PBZ group, suggesting that perioperative treatment with PBZ has some analgesic benefit. This study shows the difficulties associated with pain assessment in horses.

This study suggests that the preoperative administration of omeprazole is effective in reducing the incidence of gastro-oesophageal reflux during anaesthesia in dogs.

BackgroundThe mortality rate of horses undergoing general anaesthesia is high when compared to humans or small animal patients. One of the most critical periods during equine anaesthesia is recovery, as the horse attempts to regain a standing position. This study was performed in a private equine practice in Belgium that uses a purpose-designed one-man (head and tail) rope recovery system to assist the horse during the standing process.The main purpose of the retrospective study was to report and analyse complications and the mortality rate in horses during recovery from anaesthesia using the described recovery system. Information retrieved from the medical records included patient signalment, anaesthetic protocol, duration of anaesthesia, ASA grade, type of surgery, recovery time and complications during recovery. Sedation was administered to all horses prior to recovery with the rope system. Complications were divided into major complications in which the horse was euthanized and minor complications where the horse survived. Major complications were further subdivided into those where the rope system did not contribute to the recovery complication (Group 1) and those where it was not possible to determine if the rope system was of any benefit (Group 2).ResultsFive thousand eight hundred fifty two horses recovered from general anaesthesia with rope assistance. Complications were identified in 30 (0.51%). Major complications occurred in 12 horses (0.20%) of which three (0.05%) were assigned to Group 1 and nine (0.15%) to Group 2. Three horses in Group 2 suffered musculoskeletal injuries (0.05%). Eighteen horses (0.31%) suffered minor complications, of which five (0.08%) were categorised as failures of the recovery system.ConclusionsThis study reports the major and minor complication and mortality rate during recovery from anaesthesia using a specific type of rope recovery system. Mortality associated with the rope recovery system was low. During recovery from anaesthesia this rope system may reduce the risk of lethal complications, particularly major orthopaedic injuries.

Adjusted for CD4 cell count, incidence of TB was similar among HIV-1- and HIV-2-infected patients. Mortality rates after TB diagnosis were similar in both groups and high compared with those without TB.

We investigated the influence of the peripherally acting α2 -adrenoceptor antagonist MK-467 on the sedative and antinociceptive actions and plasma drug concentrations of medetomidine, an α2 -adrenoceptor agonist that is used in veterinary medicine as a sedative and analgesic agent. Eight healthy beagle dogs received intravenous medetomidine (10 μg/kg) or medetomidine with MK-467 (250 μg/kg) in a randomized crossover design. A standardized nociceptive pressure stimulus was applied to a nail bed of a hindlimb. Times for withdrawal of the limb and for head lift were measured, and sedation was scored. EEG data were collected prior to and after stimulation. Plasma drug concentrations were measured. Co-administration of MK-467 significantly attenuated medetomidine analgesia, as assessed with limb withdrawal, and also shortened the duration of sedation. The apparent plasma clearance of both enantiomers of medetomidine, dexmedetomidine and levomedetomidine, was more than doubled in the presence of MK-467. Antagonism by MK-467 of medetomidine-evoked vasoconstriction is seen as the mechanism behind this pharmacokinetic drug interaction. Thus, MK-467 attenuated the antinociceptive and sedative effects of medetomidine. This can probably be explained by increased clearance and decreased concentrations of dexmedetomidine in plasma after co-administration of MK-467 with racemic medetomidine.

Administration of xylazine decreases the anesthetic requirement for halothane in horses. Concurrent morphine administration to anesthetized horses does not alter the anesthetic sparing effect of xylazine or its plasma concentration-time profile.