Tocilizumab: is there life beyond anti‐TNF blockade?

Anti-TNF-α therapy has become the most effective biological treatment for rheumatoid arthritis. Despite having changed the prognosis of the disease establishing new targets for treatment strategy, there are several aspects that still remain unmatched. About 30% of the patients with rheumatoid arthritis have a less than satisfactory response to anti-TNF therapy, which has led the way for the pursuit of new targets and approaches to treatment. IL-6 is one of these alternative targets and data from the more recent clinical trials involving tocilizumab (an anti-IL-6 soluble receptor antibody) suggest advantages in relation to some clinical aspects which are not addressed by anti-TNF-α treatment.     

Routine antenatal anti‐D prophylaxis – is the protection adequate?

Background/Aims: Prophylactic anti‐D given during pregnancy can be detected in current indirect antiglobulin tests (IAT). Using this to measure the persistence of prophylactic anti‐D, this study set out to determine whether there is an association between anti‐D detectable at delivery and the RhD status of the foetus and/or the duration of the pregnancy post the standard 28 week dose of routine antenatal anti‐D prophylaxis (RAADP). The study also investigated the detection rates of anti‐D at delivery when given in a two dose regime or a one dose regime. Method: All IAT screening was undertaken using fully automated Diamed gel technology. The results from 407 women were included in the two dose regime study, and 157 in the one dose regime study. Results: 160/407 (39%) women receiving one dose of prophylactic anti‐D had no detectable anti‐D at delivery. 123/157 (78%) women on the one dose regime had no detectable anti‐D at delivery. No association was found between detectable anti‐D at delivery and the RhD status of the infant in either study arm. A strong association was found between detectable anti‐D Ig at delivery and the duration of the pregnancy post the 28 week dose in each study arm. Conclusion: Our data show that neither the two dose nor the one dose regime appear to provide adequate cover at delivery for a large percentage of pregnant women. This appears to be associated with the duration of the pregnancy past the 28 week dose but not associated with the RhD status of the foetus.     

Is there a clinical need for a diagnostic test allowing detection of chain type–specific anti‐A and anti‐B? (CME)

BACKGROUND: Hemagglutination for detection and semiquantification of ABO antibodies is associated with large center‐to‐center variations and poor reproducibility. Because acceptance for transplantation and diagnosis of rejection in ABO‐incompatible transplantation rely on the levels and specificity of ABO antibodies, reproducible tests that allow their detection and specificity determination are required. STUDY DESIGN AND METHODS: The level of chain type–specific anti‐A and anti‐B were analyzed in the sera of 44 healthy individuals of known ABO blood group using an enzyme‐linked immunosorbent assay (ELISA) with polyacrylamide (PAA) conjugates of blood group A and B trisaccharides or Type 2 chain A and B tetrasaccharides. Selected sera were further analyzed by hemagglutination and in an ELISA with Types 1 to 4 chain A or B neoglycolipids (NGL) as antigens. RESULTS: Immunoglobulin (Ig)G anti‐A and anti‐B levels were higher (p ≤ 0.05) in blood group O than in B and A individuals. More IgM anti‐A and anti‐B cross‐reactivity was detected in AB serum on PAA‐conjugated A and B trisaccharides than on the tetrasaccharides. One of 11 blood group B and two of 12 A individuals had IgG antibodies binding the tetrasaccharide despite lack of, or very low reactivity with, the trisaccharides. IgG antibodies preferring the A and B Type 2 tetrasaccharides were of the IgG2 subclass. The NGL ELISA further supported the presence of chain type–specific anti‐A and ‐B antibodies among nonsensitized, healthy individuals. CONCLUSION: An ELISA with structurally defined ABH antigens will allow the antibody class and fine specificity of ABO antibodies to be determined, which may improve risk assessment in ABO‐incompatible transplantation.     

How do I work up pretransfusion samples containing anti‐CD38?

Anti‐CD38 is used to treat relapsed or treatment‐refractory multiple myeloma. CD38 monoclonal antibodies, however, can interfere with routine blood bank serologic tests. Agglutination is observed at the indirect phase of testing as the drug binds to red blood cells (RBCs). Resolving the testing interference causes delays issuing RBC units to patients with anemia. A number of devised methods to eliminate or bypass the effects of anti‐CD38 on serologic tests are in use but no panacea exists. The limitations of each method require each testing site tailor an approach to best fit their needs. We present perspectives and testing practices from a hospital transfusion medicine service and an Immunohematology Reference Laboratory managing pretransfusion samples with anti‐CD38.     

Is ranitidine therapy sufficient for healing peptic ulcers associated with non‐steroidal anti‐inflammatory drug use?

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of serious gastroduodenal events. To minimise these risks, patients often require concomitant acid-suppressive therapy. We conducted a literature review of clinical trials examining use of ranitidine 150 mg twice daily to heal gastroduodenal ulcers (GU) in NSAID recipients. Seven studies were identified. After 8 weeks' treatment with ranitidine, GU healing rates ranged from 50% to 74% and rates of duodenal ulcer (DU) healing ranged from 81% to 84%. Ranitidine was more effective when NSAIDs were discontinued (healing rates reaching 95% and 100%, respectively). The ulcer healing rate with sucralfate was similar to that of ranitidine. However, proton pump inhibitor (PPI) therapy was associated with significantly greater rates of both GU and DU healing than ranitidine; 8-week GU rates were 92% and 88% with esomeprazole 40 mg and 20 mg, respectively (vs. 74% with ranitidine, p < 0.01). For omeprazole, 8-week healing rates were 87% with omeprazole 40 mg and 84% with omeprazole 20 mg (vs. 64% for ranitidine, p < 0.001), and for lansoprazole the corresponding values were 73-74% and 66-69% for the 30 mg and 15 mg doses, respectively (vs. 50-53% for ranitidine, p < 0.05). In the PPI study reporting DU healing the values were 92% for omeprazole 20 mg (vs. 81% for ranitidine, p < 0.05) and 88% for omeprazole 40 mg (p = 0.17 vs. ranitidine). NSAID-associated GU are more likely to heal when patients receive concomitant treatment with a PPI rather than ranitidine.     

Are nilotinib‐associated vascular adverse events an under‐estimated problem?

Vascular adverse events have been reported with nilotinib, a tyrosine kinase inhibitor prescribed for chronic myeloid leukaemia. However, few data specify their incidence, or whether they occur in predisposed patients. Hence, we prospectively studied 30 consecutive patients to assess the frequency of such adverse reactions and determine whether the patients presenting with these adverse events bear predisposing factors. From 3 to 73 months after nilotinib initiation, 10 of the 30 patients experienced vascular events. Three patients of these 10 were devoid of any patent cardiovascular risk factor, except for age. This study points out an occurrence more frequent than expected of vascular adverse events associated with nilotinib (> 30% vs. < 1% in summary of product characteristics), and particularly of vascular events of late onset in patients with no pre‐existing risk factors.     

Is licofelone,a dual inhibitor of cyclo‐oxygenase and 5‐lipoxygenase,a promising alternative in anti‐inflammatory therapy?

As prostaglandins and leukotrienes are critical in inflammation, dual cyclo-oxygenase and 5-lipoxygenase enzymes inhibitors, especially licofelone, are being developed by pharmaceutical companies. Experimental data indicate that licofelone shares the antipyretic, analgesic, anti-inflammatory and anti-platelet activities of conventional nonsteroidal anti-inflammatory drugs (NSAIDs), and exhibits anti-allergic properties. Although licofelone may lead to similar adverse effects on the kidney than available NSAIDs, it appeared to induce less gastrointestinal damaging effects than nonselective NSAIDs in animals. Unfortunately, preliminary clinical studies provided less impressive data with respect to efficacy. Finally, the experimental promise of licofelone as a safe and potent anti-inflammatory and analgesic agent remains to be proved in humans.     

Nursing migration: global treasure hunt or disaster‐in‐the‐making?

International nurse migration--moving from one country to another in the search of employment--is the focus of this article. The majority of member states of the World Health Organization report a shortage, maldistribution and misutilisation of nurses. International recruitment has been seen as a solution. The negative effects of international migration on the 'supplier' countries may be recognised today but are not effectively addressed. Nurse migration is motivated by the search for professional development, better quality of life and personal safety. Pay and learning opportunities continue to be the most frequently reported incentives for nurse migration, especially by nurses from less-developed countries. Career opportunities were considered key incentives for nurses emigrating from high-income countries. Language was reported to be a significant barrier. The positive global economic/social/professional development resulting from international migration needs to be weighed against a substantial 'brain and skills drain' experienced by supplier countries. The vulnerable status of migrant nurses is also of concern in certain cases. The focus on short-term solutions as opposed to resolving the problem of a worldwide shortage of nurses causes great concern. Recent initiatives attempt to curb or channel international recruitment. The delicate balance between recognising the right of individual nurses to migrate and a collective concern for the health of a nation's population must be achieved.