Growth charts for children with Ellis–van Creveld syndrome

Ellis–van Creveld (EvC) syndrome is a congenital malformation syndrome with marked growth retardation. In this study, specific growth charts for EvC patients were derived to allow better follow-up of growth and earlier detection of growth patterns unusual for EvC. With the use of 235 observations of 101 EvC patients (49 males, 52 females), growth charts for males and females from 0 to 20 years of age were derived. Longitudinal and cross-sectional data were collected from an earlier review of growth data in EvC, a database of EvC patients, and from recent literature. To model the growth charts, the GAMLSS package for the R statistical program was used. Height of EvC patients was compared to healthy children using Dutch growth charts. Data are presented both on a scale for age and on a scale for the square root of age. Compared to healthy Dutch children, mean height standard deviation score values for male and female EvC patients were −3.1 and −3.0, respectively. The present growth charts should be useful in the follow-up of EvC patients. Most importantly, early detection of growth hormone deficiency, known to occur in EvC, will be facilitated

Cost-Effectiveness of Adolescent Pertussis Vaccination for The Netherlands: Using an Individual-Based Dynamic Model

BACKGROUND: Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands. METHODS/PRINCIPAL FINDINGS: We designed a discrete event simulation (DES) model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996-2000--corrected for underreporting--to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data) and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years). In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205-6364 € per QALY) and €6371/QALY (range: 4139-9549 € per QALY) for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease. CONCLUSIONS/SIGNIFICANCE: To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in the population. This study indicates that adolescent pertussis vaccination is likely to be a cost-effective intervention for The Netherlands. The model is suited to investigate further pertussis booster vaccination strategies

The incidence of Bordetella pertussis infections estimated in the population from a combination of serological surveys.

OBJECTIVES: Bordetella pertussis circulates even in highly vaccinated populations. There is a considerable amount of infection in adults. For designing more effective vaccination schedules it is important to quantify the age-dependent relation between the number of notified cases and the number of infections. METHODS: We used a statistical relationship between the time since infection and the IgG antibody titers against pertussis toxin, derived from a longitudinal data set, to estimate time since infection for all individuals in a cross-sectional population-based study (1995-1996) based on their titers. Age-specific incidence of infection with B. pertussis was calculated and compared with the age-distribution of notified cases of pertussis in 1994-1996. RESULTS: Estimated incidence of infection was 6.6% per year for 3-79-year olds, annual incidence of notified cases 0.01%. Estimated age-specific incidence of infection was lowest for 3-4-year olds (3.3%) and increased gradually up to the age of 20-24 years (10.8%). The number of notified cases was highest for 3-9-year olds. CONCLUSIONS: In the Dutch population B. pertussis infections occur more frequently and in elder age-categories then suggested by notifications. Mathematical modeling could explore what booster vaccination strategies are most effective in reducing severe disease among not (completely) vaccinated infants

The presentation of a short adapted questionnaire to measure asthma knowledge of parents

Abstract Background The aim of this study is to establish asthma knowledge of parents of children (0–18 years) with asthma at the outpatient clinic. Methods A translated and adapted a 21 item Likert type 5 point scale questionnaire (Cronbach’s α-coefficient 0.73) was completed by 291 parents of children with asthma. Total asthma knowledge scores were associated with demographic and psychosocial variables. Results Factor analysis resulted in a new reduced 10 item questionnaire (Cronbach’s α-coefficient 0.72). Higher educational level of parents was associated with better asthma knowledge (p < 0.008 and p < 0.003). Parents showed more knowledge (p < 0.001) on non-medication questions. Asthma knowledge of the parent did not correlate with child age, gender, duration of airway problems, time since diagnosis or severity of asthma. Conclusions Education of parents concerning the working mechanism, indications and use of asthma medications are an essential part of asthma education. Asthma education should be repeated frequently to parents of children with long-term airway problems or diagnosed asthma. Special attention must be paid to parents with only high school education or less

Growth hormone analysis and treatment in Ellis-van Creveld syndrome

Little is known on growth, growth hormone (GH) levels and GH treatment in patients with Ellis-van Creveld syndrome (EvC). The aim of the present study was to assess growth, growth hormone status and the possible effectiveness of GH treatment in literature and in a small series of EvC patients. A review of literature indicated retarded growth for most EvC patients (-2 to -4.5 SDS) and minimal data on GH levels or treatment which did not allow any conclusion. We studied eight EvC patients, seven of whom were treated with GH. Four were GH deficient (GHD) and four were GH sufficient. In all patients treated with GH, first year growth velocity increased. In three of the four GHD and in one GH-sufficient patient a gain in height SDS was noted. In the present small EvC series GHD occurred more often than expected. Patient acquisition through the Growth Hormone Database will have caused a significant bias, but the present results indicate that GH treatment may improve growth in at least some patients with EvC. Therefore we conclude that EvC patients may benefit from being tested for GHD and, if indicated, treated. In addition a prospective study to evaluate GH status and linear growth in patients with EvC as well as the potential effectiveness of GH treatment is warrante

The first case of Hb Groene Hart [α119(H2)Pro→Ser, CCT→TCT (α1)] homozygosity confirms that a thalassemia phenotype is associated with this abnormal hemoglobin variant

Hb Groene Hart [a119(H2)Pro -> Ser, CCT -> TCT (alpha 1)] has been reported in heterozygotes of Moroccan origin and also in association with the common -alpha(3.7) deletion. In all cases, the mutated protein was not detectable but was apparently associated with a mild a-thalassemia (thal) phenotype, presumably due to a modification of the a-globin chain domain that is recognized by the a hemoglobin stabilizing protein (AHSP). The present case of Hb Groene Hart homozygosity, confirms that the alpha-thal phenotype is associated with this a-globin chain. Hb Groene Hart must be quite frequent not only in Morocco but probably also among the northern African coastal population

Simultaneous Detection of Haemophilus influenzae Type b Polysaccharide-Specific Antibodies and Neisseria meningitidis Serogroup A, C, Y, and W-135 Polysaccharide-Specific Antibodies in a Fluorescent-Bead-Based Multiplex Immunoassay ▿

We expanded the meningococcal serogroup A, C, Y, and W-135 multiplex immunoassay (MIA) to simultaneously detect immunoglobulin type G antibodies directed toward Haemophilus influenzae type b polysaccharide (HibPS). The monoplex HibPS assay was compared to a HibPS-specific competitive enzyme-linked immunosorbent assay and showed a good correlation (R = 0.96). Furthermore, no cross-reactivity between HibPS and the four meningococcal serogroups was detected. This pentaplex meningococcal Hib MIA is a useful tool to investigate serological responses toward different childhood PS vaccines

Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: an open-label, parallel, randomised controlled trial.

Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination offers protection for neonates against clinical pertussis until primary vaccinations, but maternal antibodies also interfere with infants' immune responses to primary vaccinations. We investigated the effect of maternal Tdap vaccination on the pertussis antibody responses of infants starting primary vaccinations at age 3 months. In an open-label, parallel, randomised, controlled trial, pregnant women aged 18-40 years with a low risk of pregnancy complications were recruited through independent midwives at 36 midwife clinics in the Netherlands and received Tdap vaccination either at 30-32 weeks of pregnancy (maternal Tdap group) or within 48 h after delivery (control group). All term-born infants were vaccinated with the diphtheria, tetanus, and pertussis-inactivated poliomyelitis-Haemophilus influenzae type B-hepatitis B six-in-one vaccine and a ten-valent pneumococcal vaccine at 3 months, 5 months, and 11 months. Randomisation was done using a number generator in a 1:1 ratio and with sealed envelopes. Participants and clinical trial staff were not masked, but laboratory technicians were unaware of study group assignments. The primary endpoint was serum IgG pertussis toxin antibody concentrations at age 3 months. Cord blood and infant blood samples were collected at age 2 months, 3 months, 6 months, 11 months, and 12 months. Analysis was done by modified intention to treat with all randomly assigned participants in case a laboratory result was available. This trial is registered with ClinicaltTrialsRegister.eu (EudraCT 2012-004006-9) and trialregister.nl (NTR number NTR4314). The trial is now closed to new participants. Between Jan 16, 2014, and March 4, 2016, 118 pregnant women were enrolled into our study, with 58 in the maternal Tdap group and 60 in the control group. The geometric mean concentration (GMC) of pertussis toxin antibodies were higher in infants in the maternal Tdap group than in the control group infants at age 3 months (GMC ratio 16·6, 95% CI 10·9-25·2) and also significantly higher compared with control infants at age 2 months. After primary vaccinations, antibody concentrations for pertussis toxin, filamentous haemagglutinin, and pertactin were significantly lower at all timepoints in infants of the maternal Tdap group than in infants in the control group. No safety issues after maternal Tdap vaccination were encountered. In view of the high pertussis toxin antibody concentrations at age 3 months, maternal vaccination supports a delay of the first pertussis vaccination in infants until at least age 3 months. Maternal antibody interference affects antibody concentrations after primary and booster vaccinations. The clinical consequences of this interference remain to be established