Live attenuated influenza vaccine (LAIV) is an intranasally administered trivalent, seasonal influenza vaccine that contains three live influenza viruses (two type A [H1N1 and H3N2 subtypes] and one type B). LAIV was effective in protecting against culture-confirmed influenza caused by antigenically matched and/or distinct viral strains in children aged ≤71 months enrolled in three phase III trials. LAIV was superior to trivalent inactivated influenza vaccine (TIV) in protecting against influenza caused by antigenically-matching viral strains in a multinational phase III trial in children aged 6-59 months. LAIV was also significantly more effective than TIV in decreasing the incidence of culture-confirmed influenza illness in two open-label studies (in children with recurrent respiratory tract illnesses aged 6-71 months and in children and adolescents with asthma aged 6-17 years). LAIV did not differ significantly from placebo in preventing febrile illnesses in adults (primary endpoint) enrolled in a phase III trial. However, LAIV significantly reduced the incidence of febrile upper respiratory tract illnesses (URTI), severe febrile illnesses, febrile URTI-related work absenteeism and healthcare provider use. In another well designed trial in adults, LAIV significantly reduced the incidence of symptomatic, laboratory-confirmed influenza compared with placebo (but not intramuscular TIV). LAIV was generally well tolerated in most age groups, with the majority of adverse events being mild to moderate in severity, and runny nose/nasal congestion being the most common. In a large phase III trial, LAIV, compared with TIV, was associated with an increased incidence of medically significant wheezing in vaccine-naive children aged <24 months and an increased incidence of hospitalization in children aged 6-11 months; LAIV is not approved for use in children <24 months. LAIV was not always associated with high rates of seroconversion/seroresponse, particularly in older children and adults, or in subjects with detectable levels of haemagglutination-inhibiting antibodies at baseline. However, LAIV did elicit mucosal (nasal) IgA antibody responses and strong cell-mediated immunity responses. Only one confirmed case of LAIV virus transmission to a placebo recipient (who did not become ill) occurred in a transmission study conducted in young children. The immunogenic response to LAIV in young healthy children was not affected by concomitant administration with other commonly administered childhood vaccines. In conclusion, intranasal LAIV seasonal influenza vaccine is effective and well tolerated in children, adolescents and adults. LAIV was more effective than TIV in children, although this advantage was not seen in adults. In the US, LAIV is indicated for the active immunization of healthy subjects aged 2-49 years against influenza disease caused by virus subtypes A and type B contained in the vaccine.
The loss of activity due to proteolysis of purified L-asparaginase and beta-galactosidase from different sources correlates with the thermal instability of the enzymes. A similar correlation is found when populations of soluble proteins from micro-organisms grown at different temperatures are compared for proteolytic susceptibility and thermal stability. It is proposed that there is a general correlation between the thermostability of proteins and their resistance to proteolysis.
Bortezomib (VELCADE) is a proteasome inhibitor that not only targets the myeloma cell, but also acts in the bone marrow micro-environment, inhibiting the binding of myeloma cells to bone marrow stromal cells, as well as demonstrating anabolic effects on bone. Intravenous bortezomib, with or without dexamethasone, is effective and well tolerated in patients with relapsed/refractory multiple myeloma, as demonstrated in the phase II CREST and SUMMIT trials, and the phase III APEX trial, and is a recommended treatment for this patient group. Based on the results of another phase III trial, the combination of bortezomib plus pegylated liposomal doxorubicin is also a recommended treatment for patients with relapsed/refractory multiple myeloma. Other bortezomib-combination regimens have demonstrated promising response data in phase II trials in patients with relapsed/refractory disease, although response and survival data for these combinations need to be confirmed in larger phase III trials. Bortezomib was effective and well tolerated when used as part of a first-line regimen in previously untreated patients with multiple myeloma. In the phase III VISTA trial in elderly patients with previously untreated multiple myeloma not eligible for transplantation, bortezomib in combination with melphalan and prednisone was effective and well tolerated and is a recommended treatment regimen for this group of patients. Preliminary data from phase II/III trials in patients with previously untreated multiple myeloma indicate a promising role for the use of bortezomib combined with various other chemotherapeutic agents as induction therapy prior to transplantation.
Ropivacaine (Naropin) is the pure S(-)-enantiomer of propivacaine, and is a long-acting amide local anaesthetic agent, eliciting nerve block via reversible inhibition of sodium ion influx in nerve fibres. Ropivacaine is a well tolerated regional anaesthetic effective for surgical anaesthesia as well as the relief of postoperative and labour pain. The efficacy of ropivacaine is similar to that of bupivacaine and levobupivacaine for peripheral nerve blocks and, although it may be slightly less potent than bupivacaine when administered epidurally or intrathecally, equi-effective doses have been established. Clinically adequate doses of ropivacaine appear to be associated with a lower incidence or grade of motor block than bupivacaine. Thus ropivacaine, with its efficacy, lower propensity for motor block and reduced potential for CNS toxicity and cardiotoxicity, appears to be an important option for regional anaesthesia and for the management of postoperative and labour pain.
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