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We studied the safety and immunogenicity of a Respiratory Syncytial Virus (RSV)-A vaccine containing subunit antigens F, G and M in older persons, and its effect on influenza vaccine immunogenicity. In a dose-ranging, placebo-controlled, blinded trial 561 adults > or =65 years of age at five Canadian sites were randomized to one intramuscular injection of either 100, 50 or 25 microg RSV-A-alum vaccine or 100 microg non-adjuvanted RSV-A vaccine, or alum-placebo. All participants were offered inactivated influenza vaccine on day 32. Immunization was well tolerated and reactogenicity was similar between the RSV and influenza vaccines and the alum-placebo. Only the 100 microg non-adjuvanted RSV vaccine achieved the primary immunogenicity outcome of eliciting a > or =4-fold rise in neutralizing antibody (NA) titres against RSV-A in > or =50% of participants at day 32. Geometric mean titres against RSV-A and -B at all points were comparable in 100 microg adjuvanted and non-adjuvanted groups. At day 32, a > or =4-fold haemagluttinin inhibition (HI) antibody response or HI > or =40 to Influenza (A-H3N2) was seen in >74% of participants; no difference was seen between groups. A subunit non-alum-containing RSV-A vaccine was well tolerated in a large population > or =65 years and did not interfere with influenza vaccine immunogenicity. This RSV-A-based vaccine demonstrated NA rise which could provide seasonal protection against severe RSV illnesses from RSV-A or -B and warrants further testing to determine its efficacy in the prevention of clinical illness in elderly persons.

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BACKGROUND: Influenza-associated morbidity and mortality has not decreased in the last decade, despite increased receipt of vaccine. To improve the immunogenicity of influenza vaccine, a high-dose (HD) trivalent, inactivated influenza vaccine was developed. METHODS: A multicenter, randomized, double-blind controlled study was conducted to compare HD vaccine (which contains 60 microg of hemagglutinin per strain) with the licensed standard-dose (SD) vaccine (which contains 15 microg of hemagglutinin per strain) in adults > or = 65 years of age. RESULTS: HD vaccine was administered to 2575 subjects, and SD vaccine was administered to 1262 subjects. There was a statistically significant increase in the rates of seroconversion and mean hemagglutination inhibition titers at day 28 after vaccination among those who received HD vaccine, compared with those who received SD vaccine. Mean postvaccination titers for individuals who received HD vaccine were 116 for H1N1, 609 for H3N2, and 69 for B strain; for those who received SD vaccine, mean postvaccination titers were as 67 for H1N1, 333 for H3N2, and 52 for B strain. The HD vaccine met superiority criteria for both A strains, and the responses for B strain met non-inferiority criteria. Seroprotection rates were also higher for those who received HD vaccine than for those who received SD vaccine vaccine, for all strains. Local reactions were more frequent in individuals who received HD vaccine, but the reactions were mild to moderate. CONCLUSIONS: There was a statistically significant increase in the level of antibody response induced by HD influenza vaccine, compared with that induced by SD vaccine, without an attendant increase in the rate or severity of clinically relevant adverse reactions. These results suggest that the high-dose vaccine may provide improved protective benefits for older adults. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00391053 .

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BACKGROUND: Respiratory syncytial virus (RSV) has been recognized recently as an important adult pathogen. METHODS: This randomized, double-blind, placebo-controlled study was designed to compare humoral responses to licensed trivalent influenza vaccine given concomitantly with 1 of 2 RSV vaccine formulations in persons > or =65 years old with cardiopulmonary disease. Hemagglutinin-inhibition assays and neutralization assays were used to measure levels of antibody to influenza and RSV, respectively. Subjects with respiratory illnesses during subsequent winters were tested for RSV and influenza by reverse-transcriptase polymerase chain reaction and serologic analysis. RESULTS: Neither RSV vaccine formulation had an effect on the humoral response to influenza vaccination, and both RSV vaccines were well tolerated by 1169 participants. The immunogenicity of the nonadjuvanted vaccine was judged superior on the basis of mean postvaccination neutralizing antibody titers (12.5 vs. 12.1) and the percentage of subjects for whom > or =4-fold increases in neutralizing titer were observed when acute-phase and convalescent-phase serum samples were compared (168 [44%] of 383 vs. 129 [33%] of 400). In year 1, the percentage of illnesses due to RSV was 7% (36 of 492 illnesses) and that due to influenza was 8% (40 of 492), compared with 6% (11 of 189) due to RSV and 11% (20 of 189) due to influenza in year 2. The incidence of RSV infection was not significantly different in the RSV vaccine and placebo groups. CONCLUSIONS: Although the safety and immunogenicity data of these RSV vaccines are encouraging, low rates of infection make it challenging to design efficacy trials.

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To improve immune responses to influenza vaccine, a trivalent inactivated vaccine containing 60 microg of the HA of each component (A/H3N2, A/H1N1, B) was compared to a licensed vaccine containing 15 microg of the HA of each. More local and systemic reactions were reported by subjects given the high dosage but only local pain and myalgias were significantly increased. The high dosage vaccine induced a higher frequency of serum antibody increases (> or =4-fold) in both hemagglutination-inhibiting (HAI) and neutralization tests for all three vaccine viruses in the total group as well as subjects vaccinated and those not vaccinated the previous year. Mean titers of antibody attained, the magnitude of antibody increases and the frequencies of persons with final HAI antibody titers > or =1:32, > or =1:64, and > or =1:128 were all greater for the high dosage group in both serologic tests, for all groups, and for all vaccine viruses. These increased immune responses should provide increased protection against influenza in the elderly.

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Introducción: El 131I es una opción terapéutica eficaz para el tratamiento del hipertiroidismo, aunque en un alto porcentaje de pacientes se desarrolla hipotiroidismo definitivo. Objetivo: Evaluar la función tiroidea a largo plazo de pacientes con hipertiroidismo tras el tratamiento con 131I. Pacientes y método: Se estudió retrospectivamente a 128 pacientes hipertiroideos que recibieron 131I entre 1994 y 1999. Se excluyó a 32 por pérdida en el seguimiento y se clasificó a los 96 sujetos incluidos, según la afección tiroidea, en GB (Graves-Basedow, n = 46), BMN (bocio multinodular, n = 35) y AT (adenoma tóxico, n = 15). El tiempo de seguimiento fue 7,3 ± 0,2 años y la dosis media de 131I, 12,2 ± 0,3 mCi. Resultados: De los 96 pacientes, en el 58,3% se desarrolló hipotiroidismo, el 34,4% mantenía normofunción tiroidea y el 7,3% restante permanecía con hiperfunción clínica o subclínica. El 19,8% (n = 19) precisó más de una dosis de 131I. En el grupo GB, el 87% evolucionó a hipotiroidismo, el 10,9% persistía eutiroideo y el 2,1%, con hiperfunción; recibieron 2 dosis de 131I 10 (21,7%) pacientes. Del grupo BMN, el 28,6% quedó hipotiroideo; el 54,3%, eutiroideo y el 17,1%, con hiperfunción; 7 (20%) pacientes necesitaron 2 dosis y 2 (5,7%) pacientes, 3 dosis. En el grupo AT, el 40% desarrolló hipotiroidismo y el 60% mantenía normofunción tiroidea; 2 (13,3%) pacientes recibieron 2 dosis. Conclusiones: La tasa de hipotiroidismo definitivo en el grupo GB es superior a la de los otros 2 grupos. El alto porcentaje de pacientes con BMN que persisten hipertiroideos tras 131I indica que son necesarias dosis superiores en este grupo

Background: Radioiodine treatment is a safe and effective therapeutic option for hyperthyroidism, although the incidence of subsequent definitive hypothyroidism is high. Objective: To evaluate long-term thyroid function after radioiodine treatment in hyperthyroid patients. Patients and method: We performed a retrospective study of 128 hyperthyroid patients administered 131I between 1994 and 1999. We excluded 32 patients who were lost to follow-up. The 96 patients included were categorized into Graves' disease (GD), n = 46, toxic multinodular goiter (TMG), n = 35, and toxic adenoma (TA), n = 15. The mean time of follow-up was 7.3 ± 0.2 years and the mean 131I dose was 12.2 ± 0.3 mCi. Results: Among the 96 patients, hypothyroidism developed in 58.3%, normal thyroid function was achieved in 34.4% and some degree of hyperthyroidism persisted in 7.3%. More than one radioiodine dose was required in 19.8% (n = 19). In GD patients, hypothyroidism appeared in 87%, euthyroidism was achieved in 10.9%, and hyperthyroidism persisted in 2.1%. Ten patients required second 131I doses. In the TMG group, hypothyroidism developed in 28.6%, euthyroidism was achieved in 54.3% and hyperthyroidism was present in 17.1%. Seven patients (20%) were administered a second radioiodine dose and two patients (5.7%) received a third dose. In the TA group, hypothyroidism developed in 40% and euthyroidism was achieved in 60%. Two patients (13.3%) received a second 131I dose. Conclusions: The incidence of definitive hypothyroidism was higher in the GD group than in the TMG and TA groups. The high percentage of TMG patients with persistent hyperthyroidism suggests the need for higher radioiodine doses in this group

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