An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine

BACKGROUND: In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron(R)) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, polio, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany. METHODS: Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6--8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study. RESULTS: In the intent-to-treat population, paracetamol reduced the incidence of fever >=38[degree sign]C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39[degree sign]C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39[degree sign]C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported. CONCLUSIONS: Paracetamol effectively prevented fever and other reactions, mainly during the infant series. However, as events were generally mild and of no concern in either group our data support current recommendations to administer paracetamol to treat symptoms only and not for routine prophylaxis.Trial registration: NCT00294294

Mode-specific impact of relaxation training for hypertensive men with type a behavior pattern

Multimodal therapy calls for selection of interventions on the basis of the specific modes of functioning that they are expected to affect. Mode-specificity assumptions were tested in a study of progressive muscle relaxation (PMR) training for type A men with borderline hypertension. It was expected that PMR would be especially effective in reducing psychophysiological reactivity and not effective for hostile cognition or behavioral anger expression. Forty-three subjects were randomly assigned to a control group receiving medical information or to information + PMR. PMR subjects reduced blood pressure reactivity to an anger-instigating role-play more than did controls. Although trait questionnaire measures of hostility and outward anger expression showed no group differences, a think-aloud measure of hostility and an observational measure of anger expression favored PMR. Discussion focuses on alternative explanations for these results, including the possibility that measures failing to show treatment effects were those confounded with negative affectivity

L'Athlète : journal hebdomadaire de tous les sports

18 avril 19281928/04/18 (N570)-1928/04/18.Appartient à l’ensemble documentaire : Aquit

Safety and immunogenicity of fully liquid and lyophilized formulations of an investigational trivalent group B streptococcus vaccine in healthy non-pregnant women: Results from a randomized comparative phase II trial

BACKGROUND: We evaluated the safety and immunogenicity of liquid and lyophilized formulations of an investigational trivalent group B streptococcus (GBS) vaccine in non-pregnant women and assessed the formulations' equivalence in terms of serotype-specific immune response. METHODS: This phase II, randomized, comparative, observer-blind trial enrolled healthy non-pregnant women 18-40 years of age. Women received a single dose of fully liquid (n = 529) or lyophilized (n = 521) trivalent GBS vaccine on day 1. Safety assessments were performed up to day 181 (study termination). Serotype Ia/Ib/III-specific immunoglobulin G (IgG) antibodies were measured in sera from women on day 1 (pre-vaccination) and day 31. Equivalence between the two formulations was demonstrated if the two-sided 95% confidence interval (CI) for the ratio (liquid/lyophilized) of the geometric mean concentrations (GMCs) on day 31 was contained in a (0.5, 2.0) interval for each serotype. RESULTS: Solicited and unsolicited adverse events were reported at similar rates for both formulations. Serious adverse events were reported for six (1.1%) liquid GBS and nine (1.7%) lyophilized GBS vaccinated women, none of which were considered related to vaccination or fatal. On day 31, serotype-specific IgG concentrations were 8-16-fold higher than on day 1 in both groups. Equivalence of the liquid to the lyophilized formulation 30 days post-vaccination was demonstrated as the 95% CIs of the GMC ratios were within the pre-specified interval for the three serotypes: GMC ratios were 1.02 (95% CI: 0.79, 1.32) for serotype Ia, 0.93 (0.71, 1.21) for serotype Ib and 0.99 (0.76, 1.30) for serotype III. CONCLUSIONS: Both formulations of the investigational trivalent GBS vaccine had favorable safety profiles and induced similar GBS serotype-specific antibody concentrations. This study demonstrated that the fully liquid formulation was equivalent to the lyophilized formulation in healthy non-pregnant women in terms of immunogenicity for all three serotypes. CLINICAL TRIALS REGISTRATION: NCT02270944.status: publishe