Safety and effectiveness of recombinant factor XIII-A in congenital factor XIII deficiency: Real-world evidence.

Background: Regular factor XIII (FXIII) prophylaxis is standard treatment for congenital FXIII A-subunit deficiency (FXIII-A CD). Recombinant factor XIII-A (rFXIII-A) was extensively evaluated in the mentor trials.

Objective: To assess real-world safety and treatment effectiveness of rFXIII-A prophylaxis from the mentor 6 trial.

Nonacog beta pegol (N9-GP) in hemophilia B: First report on safety and efficacy in previously untreated and minimally treated patients.

Background/objective: We report the first analysis of an extended half-life recombinant factor IX, nonacog beta pegol (N9-GP), in previously untreated patients (PUPs) and minimally treated patients with hemophilia B.

Methods: Paradigm 6 (Safety and Efficacy of Nonacog Beta Pegol [N9-GP] in Previously Untreated Patients With Haemophilia B) is a multicenter, open-label, single-arm, phase 3 trial. Main inclusion criteria were males aged < 6 years, with hemophilia B with factor IX (FIX) activity ≤ 2%, who were previously untreated or with ≤ 3 exposure days (EDs) to FIX-containing products.

BCG scarring and improved child survival: a combined analysis of studies of BCG scarring.

Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) is recommended at birth in TB-endemic areas. Currently, BCG vaccination programmes use "BCG vaccination coverage by 12 months of age" as the performance indicator. Previous studies suggest that BCG-vaccinated children, who develop a scar, have better overall survival compared with BCG-vaccinated children, who do not develop a scar.

Favorable pharmacokinetics in hemophilia B for nonacog beta pegol versus recombinant factor IX-Fc fusion protein: A randomized trial.

Background And Objective: Nonacog beta pegol (N9-GP) and recombinant factor IX-Fc fusion protein (rFIXFc) are extended half-life rFIX compounds. We report the first single-dose pharmacokinetic trial of N9-GP and rFIXFc.

Patients/methods: Paradigm 7 was a multicenter, open-label, randomized, crossover trial in previously treated (>150 exposure days) adults with congenital hemophilia B (FIX activity ≤2%).

Recombinant FXIII (rFXIII-A2) Prophylaxis Prevents Bleeding and Allows for Surgery in Patients with Congenital FXIII A-Subunit Deficiency.

Recombinant factor XIII-A (rFXIII-A) was developed for prophylaxis and treatment of bleeds in patients with congenital FXIII A-subunit deficiency. mentor™2 (NCT00978380), a multinational, open-label, single-arm, multiple-dosing extension to the pivotal mentor™1 trial, assessed long-term safety and efficacy of rFXIII-A prophylaxis in eligible patients (patients with severe [<0.05 IU/mL] congenital FXIII subunit A deficiency) aged ≥6 years.

Randomized Trial of 2 Versus 1 Dose of Measles Vaccine: Effect on Hospital Admission of Children After 9 Months of Age.

Background: Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investigated the effect on hospital admissions.

Recombinant factor XIII prophylaxis is safe and effective in young children with congenital factor XIII-A deficiency: international phase 3b trial results.

Unlabelled: Essentials Prophylaxis is the standard of care for congenital factor XIII-A (FXIII-A) deficiency. Six children with FXIII-A deficiency received once-monthly prophylaxis with recombinant FXIII-A. Prophylaxis was well tolerated and no anti-FXIII antibodies were detected.

Comparison of F13A1 gene mutations in 73 patients treated with recombinant FXIII-A.

Introduction: Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder usually caused by mutations in the F13A1 gene that produce a severe quantitative (type I) deficiency of the FXIII-A subunit.

Aim: To determine the genotypes of patients with severe FXIII-A deficiency treated with recombinant FXIII-A subunit (rFXIII-A ) participating in three international efficacy and safety trials.

Methods: We determined the genotypes of 73 patients in total; 32 had already undergone genotype analysis and were known to carry F13A1 mutations that have been previously reported in the literature.

Developing the First Recombinant Factor XIII for Congenital Factor XIII Deficiency: Clinical Challenges and Successes.

Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder with potentially life-threatening consequences. FXIII is composed of two subunits (A and B), and a deficiency or dysfunction of either can result in FXIII deficiency. Traditionally, FXIII deficiency has been managed by infusing plasma-derived products containing FXIII (fresh frozen plasma, cryoprecipitate, and plasma-derived FXIII concentrates), all of which contain both subunits.

Interaction between neonatal vitamin A supplementation and timing of measles vaccination: a retrospective analysis of three randomized trials from Guinea-Bissau.

Background: In Guinea-Bissau we conducted three trials of neonatal vitamin A supplementation (NVAS) from 2002 to 2008. None of the trials found a beneficial effect on mortality. From 2003 to 2007, an early measles vaccine (MV) trial was ongoing, randomizing children 1:2 to early MV at 4.

A randomized trial of an early measles vaccine at 4½ months of age in Guinea-Bissau: sex-differential immunological effects.

Background: After measles vaccine (MV), all-cause mortality is reduced more than can be explained by the prevention of measles, especially in females.

Objective: We aimed to study the biological mechanisms underlying the observed non-specific and sex-differential effects of MV on mortality.

Methods: Within a large randomised trial of MV at 4.

Measles vaccination in the presence or absence of maternal measles antibody: impact on child survival.

Background: Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present.

Methods: To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data from 2 previously published randomized trials of a 2-dose schedule with MV given at 4-6 months and at 9 months of age. In both trials antibody levels had been measured before early measles vaccination.

Measles virus antibody responses in children randomly assigned to receive standard-titer edmonston-zagreb measles vaccine at 4.5 and 9 months of age, 9 months of age, or 9 and 18 months of age.

The World Health Organization recommends administration of measles vaccine (MV) at age 9 months in low-income countries. We tested the measles virus antibody response at 4.5, 9, 18, and 24 months of age for children randomly assigned to receive standard-titer Edmonston-Zagreb MV at 4.

A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given at 4.5 months of age: effect on total hospital admissions.

Observational studies and trials from low-income countries indicate that measles vaccine has beneficial nonspecific effects, protecting against non-measles-related mortality. It is not known whether measles vaccine protects against hospital admissions. Between 2003 and 2007, 6417 children who had received the third dose of diphtheria, tetanus, and pertussis vaccine were randomly assigned to receive measles vaccine at 4.

Measles antibody levels after vaccination with Edmonston-Zagreb and Schwarz measles vaccine at 9 months or at 9 and 18 months of age: a serological study within a randomised trial of different measles vaccines.

Unlabelled: Standard-titre Schwarz (SW) and Edmonston-Zagreb (EZ) measles vaccines (MV) are both used in the routine immunisation programme. Within a trial of different strains of MV, we examined antibody responses in both one-dose and two-dose schedules when the first dose was administered at 9 months.

Setting And Methods: The trial was conducted in an urban area in Guinea-Bissau where we have had a health and demographic surveillance system and studied strategies to prevent measles infection since 1978.

The optimal age of measles immunisation in low-income countries: a secondary analysis of the assumptions underlying the current policy.

Objective: The current policy of measles vaccination at 9 months of age was decided in the mid-1970s. The policy was not tested for impact on child survival but was based on studies of seroconversion after measles vaccination at different ages. The authors examined the empirical evidence for the six underlying assumptions.

Risk factors for measles in young infants in an urban African area with high measles vaccination coverage.

Background: We examined risk factors for measles infection before measles vaccination at 9 months of age in Guinea-Bissau.

Methods: Among 1524 children enrolled in a trial of early measles vaccination at 4.5 months of age, we assessed the relative risk (RR) of measles before enrollment and the incidence rate ratio between 4.

The effect of high-dose vitamin A supplementation at birth on measles incidence during the first 12 months of life in boys and girls: an unplanned study within a randomised trial.

Vitamin A treatment reduces mortality during acute measles infection, and vitamin A supplementation (VAS) to children above 6 months of age may reduce the incidence of measles infection. The effect of VAS at birth on measles incidence is unknown. In a randomised placebo-controlled trial in Guinea-Bissau, normal-birth-weight newborns were randomised to 50 000 IU (15 mg) VAS or placebo.

Non-specific effects of standard measles vaccine at 4.5 and 9 months of age on childhood mortality: randomised controlled trial.

Objective: To examine in a randomised trial whether a 25% difference in mortality exists between 4.5 months and 3 years of age for children given two standard doses of Edmonston-Zagreb measles vaccines at 4.5 and 9 months of age compared with those given one dose of measles vaccine at 9 months of age (current policy).

Sex differences in the effect of vaccines on the risk of hospitalization due to measles in Guinea-bissau.

Background: Routine immunizations have non-specific and sex-differential effects on childhood mortality and morbidity in low-income countries; BCG and measles vaccine (MV) may reduce and diphtheria-tetanus-pertussis vaccine (DTP) may increase the mortality of girls relative to boys.

Setting: Urban area in Guinea-Bissau, with a demographic surveillance system and registration of all pediatric hospitalizations. Guinea-Bissau experienced a large outbreak of measles infection in 2003-2004.

Girls may have lower levels of maternal measles antibodies and higher risk of subclinical measles infection before the age of measles vaccination.

Background: Previous studies have suggested that girls may have lower maternal measles antibody levels than boys. Girls might therefore be more likely to contract measles infection before the normal age of measles vaccination at 9 months of age.

Methods: In connection with a clinical trial of different measles vaccination strategies, we collected pre-measles vaccination blood samples at 4.

Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial.

Objective: To examine the protective efficacy of measles vaccination in infants in a low income country before 9 months of age.

Design: Randomised clinical trial.

Participants: 1333 infants aged 4.

Thymus size at 6 months of age and subsequent child mortality.

Objective: To examine determinants of thymus size at age 6 months and investigate whether thymus size at this age is a determinant of subsequent mortality.

Study Design: Thymus size was measured by transsternal sonography in 923 6-month-old children participating in a measles vaccination trial in Guinea-Bissau.

Results: Thymus size was strongly associated with anthropometric measurements.

A comparison of ex vivo cytokine production in venous and capillary blood.

We performed a randomized study of the immunological effects of an early measles vaccine given at 4.5 months of age and aimed to obtain venous samples from the infants at baseline and 6 weeks later. If this was not feasible, a capillary sample was obtained.

Increased female-male mortality ratio associated with inactivated polio and diphtheria-tetanus-pertussis vaccines: Observations from vaccination trials in Guinea-Bissau.

Background: The 2-fold increase in female mortality after high-titer measles vaccine may have occurred because many children received diphtheria-tetanus-pertussis (DTP) vaccine or inactivated polio vaccine (IPV) after high-titer measles vaccine.

Objective: We examined whether DTP vaccine and IPV were associated with increased female mortality when they were the most recent vaccine administered to children who had not received measles vaccine.

Setting And Design: IPV was used as a control vaccine in 4 randomized trials of early measles vaccination (MV) with enrollment at 4-6 months of age conducted in Guinea-Bissau.