Objective: To audit the accuracy of dose administration aid (DAA) packaging in regional aged care facilities (RACFs) within the boundaries of the Hunter Urban Division of General Practice. Design, participants and setting: Each participating RACF audited one DAA for each resident receiving medication between May and August 2006. Registered nurses compared the contents with the medication chart prepared by the general practitioner and recorded any discrepancies as incidents. Main outcome measures: Number of medication incidents in the provision of DAAs. Results: 297 incidents were detected from 6972 packs for 2480 residents (incident rate of 4.3% of packs and 12% of residents) from 42 participating RACFs. Reasons for incidents included medications missing from a pack (99 occasions), wrong medication dispensed (12), supply of the wrong strength (32), incorrect labelling (7), pharmacies supplying medication that had been ceased by the GP (37), incorrect dosage instructions (32), medications not delivered to the RACF (13). Conclusion: The rate of incidents in DAA packaging in RACFs was high. The error types included incorrect packaging, correct packaging but the DAA was no longer required, and operational problems. Recommendations for improvement include: continuing audit and analysis by RACFs; streamlining of communications among GPs, pharmacists and RACF staff; using electronic methods to chart, order and dispense medications; use of generic names as much as possible; development of guidelines for the supply of medication in DAAs.

Esomeprazole is an effective, well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis and overall, provided better efficacy than omeprazole. Notably, in a large (n >5000 patients) double-blind trial, esomeprazole 40mg provided significantly better efficacy than lansoprazole in terms of healing rates and resolution of symptoms. Long-term therapy with esomeprazole maintained healed oesophagitis in these patients. Esomeprazole also proved beneficial in patients with symptomatic GORD without oesophagitis. Thus, esomeprazole has emerged as an option for first-line therapy in the management of acid-related disorders.

Heart failure continues to be a major global health problem with a pronounced impact on morbidity and mortality and very limited drug treatment options especially with regard to inotropic therapy. Omecamtiv mecarbil is a first-in-class cardiac myosin activator, which increases the proportion of myosin heads that are tightly bound to actin and creates a force-producing state that is not associated with cytosolic calcium accumulation. Phase I and phase II studies have shown that it is safe and well tolerated. It produces dose-dependent increases in systolic ejection time (SET), stroke volume (SV), left ventricular ejection fraction (LVEF), and fractional shortening. In the ATOMIC-AHF trial, intravenous (IV) omecamtiv mecarbil did not improve dyspnoea overall but may have improved it in a high-dose group of acute heart failure patients. It did, however, increase SET, decrease left ventricular end-systolic diameter, and was well tolerated. The COSMIC-HF trial showed that a pharmacokinetic-based dose-titration strategy of oral omecamtiv mecarbil improved cardiac function and reduced ventricular diameters compared to placebo and had a similar safety profile. It also significantly reduced plasma N-terminal-pro B-type natriuretic peptide compared with placebo. The GALACTIC-HF trial is now underway and will compare omecamtiv mecarbil with placebo when added to current heart failure standard treatment in patients with chronic heart failure and reduced LVEF. It is expected to be completed in January 2021. The ongoing range of preclinical and clinical research on omecamtiv mecarbil will further elucidate its full range of pharmacological effects and its clinical usefulness in heart failure.

We have analysed the published literature on eptacog alfa (recombinant factor VIIa; rFVIIa) for nonhaemophiliac conditions with the aim of determining its current place in therapy. Initial surgical and/or medical management is required for any patient with life-threatening bleeding. In those with continued life-threatening bleeding (i.e. despite maximal surgical and/or medical therapy), eptacog alfa may be considered as additional therapy, in exceptional circumstances. There is good evidence from systematic reviews and randomized controlled trials (RCTs) that eptacog alfa stops bleeding in adults with intracerebral haemorrhage (ICH) if it is given within 4 hours of symptom onset. However, a recent phase III RCT suggests that it does not improve clinically relevant long-term outcomes (death and disability). There is also good evidence against prophylactic use of eptacog alfa during orthotopic liver transplantation or liver resection, and in treating variceal and nonvariceal haemorrhage in patients with cirrhosis. The evidence for the use of eptacog alfa for unexpected life-threatening bleeding in liver, cardiac or other surgery, or in blunt trauma, is not robust. In these circumstances, it should only be given as part of a clinical trial or in exceptional cases when other therapies have failed. The evidence for use of eptacog alfa in penetrating trauma is lacking. Conflicting RCT results exist for the prophylactic use of eptacog alfa in elective surgery; therefore, it cannot be recommended in this situation. There is insufficient evidence for a primary role of eptacog alfa in reversal of anticoagulation with heparin-like molecules and novel anticoagulant agents. There are effective therapies that correct all warfarin-induced factor deficiencies; thus, off-label use of eptacog alfa for reversal of warfarin should only be considered in the context of ICH. The evidence for eptacog alfa use in children is limited. The only RCT is in cardiac surgery for congenital heart disease, where eptacog alfa prophylaxis was actually associated with increased time to chest closure. It may be of potential benefit in some children with life-threatening bleeding in the context of trauma, surgery or liver disease (as additional therapy when surgical and/or medical control of bleeding has failed), but the overall benefit-risk ratio may be unfavourable if there is an underlying risk of thromboembolism (e.g. trauma, congenital heart disease, other hyperviscous or hypercoagulable states, presence of arterial or central venous catheters). Thromboembolism may be associated with eptacog alfa use. Although the magnitude of this risk and possible predisposing factors are not clearly delineated, some data suggest increased risk at higher doses. Variable effects of eptacog alfa use on mortality have been shown in a pooled analysis of RCTs. Data from some observational studies and postmarketing surveillance suggest an increased risk of thromboembolism associated with off-label uses. Further well designed studies are required to more definitively ...

Adalimumab (ADA) is a subcutaneously (SC) self-administered fully human Ig G1 monoclonal antibody directed against tumor necrosis factor alpha (TNF). In the CLASSIC I dose-ranging trial, ADA was superior to placebo for inducing remission in patients with moderate-to-severe Crohn's disease (CD) naive to TNF inhibitor therapy. In CLASSIC II, patients in remission following CLASSIC I maintained remission for up to 56 weeks while on ADA. In CHARM, approximately 40% of the 499 patients with moderate-to-severe CD who responded to ADA, maintained remission at 26 and 52 weeks, thus confirming long-term efficacy. ADA demonstrated steroid-sparing properties, beneficial effects in patients with perianal fistulas, and decreases in rates of hospitalization and surgery. Sub-group analyses demonstrated similar remission rates irrespective of concomitant immunosuppressive use or previous exposure to other TNF inhibitor therapy. In the GAIN trial, 325 patients who had either lost response or become intolerant to infliximab (IFX) were randomized to recieve ADA induction therapy or placebo. In this difficult-to-treat patient population, 21% achieved remission and half demonstrated clinical benefit from ADA induction therapy. Injection site reactions may occur with SC ADA (2-5% of patients), which are generally less dramatic in nature than infusion reactions experienced with intravenous IFX. Immunogenicity occurs with all monoclonal antibodies; however, in the CD development program anti-ADA antibodies were detected at low rates (0.7 and 2.6% of patients in the CLASSIC I and CLASSIC II studies, respectively). Based on robust short-and long-term efficacy data from large randomized controlled trials and a favorable safety signal, ADA has become a key addition to the therapeutic armamentarium in the treatment of moderate-to-severe CD.

Cardiovascular disease (CVD) has consistently been the leading cause of death worldwide. Several clinical and epidemiological studies have demonstrated that an elevated plasma concentration of lipoprotein (a) [Lp(a)] is a causative and independent major risk factor for the development of CVD, as well as calcific aortic valve stenosis. Thus, the therapeutic management of hyperlipoproteinemia (a) has received much attention, as significant reductions in Lp(a) levels may, potentially, favorably affect cardiovascular risk. Aspirin, niacin, estrogens, and statins, which act on different molecular pathways, may be prescribed to patients with mild or modest elevations of Lp(a) levels. Other therapeutic interventions, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, Lp(a) apheresis, and the novel antisense oligonucleotides APO(a)-Rx and APO(a)-LRx, which are being evaluated in ongoing clinical trials, have provided some promising results and can potentially be used in severe cases of hyperlipoproteinemia (a). This review aims to present and discuss the current clinical and scientific data pertaining to the therapeutic options for the management of hyperlipoproteinemia (a).

The effects of indomethacin, dazoxiben and EPO45 on collagen-induced platelet aggregation in vivo were studied in guinea-pigs and rats to determine the involvement of the prostaglandin endoperoxide/thromboxane A2 pathway in the aggregatory response. Indomethacin and EPO45 (a thromboxane receptor antagonist) partially inhibited platelet aggregation in rats. It was concluded that only one third of the aggregatory response to collagen was mediated by the products of cyclo-oxygenase conversion of arachidonic acid. In rats, dazoxiben was inactive although the conversion of the prostaglandin endoperoxides to thromboxane A2 was inhibited (measured as thromboxane B2). 6-keto PGF1 alpha was detected in plasma after collagen was injected into dazoxiben-treated rats. In this species therefore, the endoperoxides have significant aggregatory activity whilst the apparent increase in the level of prostacyclin was not sufficient to have any anti-aggregatory effect. All three drugs were active in the guinea-pig. About 60% of the aggregatory response to collagen was due to the products of the cyclo-oxygenase pathway, the main mediator being thromboxane A2. In guinea-pigs, dazoxiben also elevated 6-keto PGF1 alpha in the plasma after an injection of collagen. However, this apparent increase in prostacyclin production did not contribute to the anti-aggregatory effect.

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