Anne G. M. Schilder

Effect of conjugate pneumococcal vaccine followed by polysaccharide pneumococcal vaccine on recurrent acute otitis media: a randomised study.

BACKGROUND Pneumococcal conjugate vaccine prevents recurrent acute otitis media (AOM) in infants immunised at 2, 4, 6, and 12-15 months of age. We aimed to find out whether this vaccine also prevents AOM in older children who have had previous episodes of AOM. METHODS In this double-blind, randomised study, we enrolled 383 patients aged 1-7 years who had had two or more episodes of AOM in the year before entry. Randomisation was stratified in four groups according to age (12-24 months vs 25-84 months) and the number of previous AOM episodes (two or three episodes vs four or more episodes). Children received either 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine, or hepatitis A or B vaccines. They were followed up for 18 months for recurrence of AOM. We also cultured samples of middle-ear fluid and nasopharyngeal swabs to assess association of pneumococcal serotypes with AOM after vaccination. FINDINGS We noted no reduction of AOM episodes in the pneumococcal vaccine group compared with controls (intention-to-treat analysis: rate ratio 1.25, 95% CI 0.99-1.57). Although nasopharyngeal carriage of pneumococci of serotypes included in the conjugate-vaccine was greatly reduced after pneumococcal vaccinations, immediate and complete replacement by non-vaccine pneumococcal serotypes took place. INTERPRETATION These data do not lend support to the use of pneumococcal conjugate vaccine to prevent otitis media in previously unvaccinated toddlers and children with a history of recurrent AOM.

National differences in incidence of acute mastoiditis: relationship to prescribing patterns of antibiotics for acute otitis media?

BACKGROUND Operating on the principle that most acute otitis media (AOM) episodes resolve without antibiotics, doctors in the Netherlands usually manage AOM in children with initial observation. Prescription of antibiotics is limited to children with a complicated course of AOM and those categorized as high risk. Consequently only 31% of patients with AOM receives antibiotics, compared with >90% in most other countries. OBJECTIVE To substantiate the suggestion that this restrictive use of antibiotics leads to a higher incidence of acute mastoiditis. METHODS A comparative study across several European countries, Canada, Australia and the United States was performed in the period 1991 to 1998. The incidence rate of acute mastoiditis was defined as the total number of patients age 14 years and younger discharged from all hospitals with the primary diagnosis of acute mastoiditis, during a specified period (usually 5 years), divided by the number of person years (py) in that same age range and period. The latter was calculated by totaling the midyear population estimate of children age 14 years and younger of each year. The 95% confidence intervals and incidence rate ratios were calculated to compare the observed rates. RESULTS The incidence rate of acute mastoiditis in the Netherlands, with a low antibiotic prescription rate for AOM, was 3.8/100,000 py; in Norway and Denmark, with high prescription rates, the incidence rate was comparable at 3.5/100,000 py and 4.2/100,000 py, respectively. In all other countries with very high prescription rates, incidence rates were considerably lower, ranging from 1.2 to 2.0/100,000 py. The incidence rate in the Netherlands was about twice that in the United States (rate ratio, 0.5). CONCLUSION The incidence rate of acute mastoiditis in the Netherlands is higher than in many countries with higher antibiotic prescription rates. Although the potential benefits of restricted use of antibiotics (i.e. cost reduction, fewer side effects from antibiotics and less antimicrobial resistance) are beyond dispute, such strategy may be associated with a somewhat higher incidence of acute mastoiditis.

Effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy: open, randomised controlled trial

Abstract Objective To assess the effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy. Design Open, randomised controlled trial. Setting 21 general hospitals and three academic centres in the Netherlands. Participants 300 children aged 2-8 years requiring adenotonsillectomy. Intervention Adenotonsillectomy compared with watchful waiting. Main outcome measures Episodes of fever, throat infections, upper respiratory tract infections, and health related quality of life. Results During the median follow up period of 22 months, children in the adenotonsillectomy group had 2.97 episodes of fever per person year compared with 3.18 in the watchful waiting group (difference −0.21, 95% confidence interval −0.54 to 0.12), 0.56 throat infections per person year compared with 0.77 (−0.21, −0.36 to −0.06), and 5.47 upper respiratory tract infections per person year compared with 6.00 (−0.53, −0.97 to −0.08). No clinically relevant differences were found for health related quality of life. Adenotonsillectomy was more effective in children with a history of three to six throat infections than in those with none to two. 12 children had complications related to surgery. Conclusion Adenotonsillectomy has no major clinical benefits over watchful waiting in children with mild symptoms of throat infections or adenotonsillar hypertrophy.

Trends in Doctor Consultations, Antibiotic Prescription, and Specialist Referrals for Otitis Media in Children: 1995–2003

BACKGROUND. Reported trends regarding the incidence of otitis media and antibiotic prescription rates are inconsistent. OBJECTIVE. Our goal was to assess changes in incidence of consultation rates, antibiotic prescription, and referral rates for otitis media in children over the years 1995–2003. METHODS. A cohort study including all children aged 0 to 13 years within the research database of the Netherlands University Medical Center Utrecht Primary Care Network covering the period 1995–2003. Otitis media diagnoses were recorded according to the International Classification of Primary Care codes and antibiotic prescription according to the Anatomic Therapeutic Chemical Classification System codes. Otitis media incidence rates were calculated as episodes per 1000 person-years. Antibiotic prescription and referral rates were calculated per 100 otitis media episodes. RESULTS. From 1995 to 2003, the overall general practitioner consultation rates for acute otitis media and otitis media with effusion declined by 9% and 34%, respectively. In children aged 2 to 6 years and those aged 6 to 13 years, the incidence rates of acute otitis media and otitis media with effusion declined by 15% and 41% and 40% and 48%, respectively. In children <2 years of age, the incidence rates of acute otitis media and otitis media with effusion increased by 46% and 66%, respectively. Antibiotic prescription rates for acute otitis media and otitis media with effusion increased by 45% and 25%, respectively. The referral rate for acute otitis media did not change, whereas the referral rate for otitis media with effusion increased by 45%. CONCLUSIONS. Consultation rates for otitis media have changed considerably over the last decade, and so have antibiotic prescriptions and specialist referrals. The rising antibiotic prescription rate for otitis media causes concern, because this may induce increasing medical costs and antibiotic resistance.

Nasopharyngeal pneumococcal carriage after combined pneumococcal conjugate and polysaccharide vaccination in children with a history of recurrent acute otitis media

BACKGROUND We recently showed that vaccination with a 7-valent pneumococcal conjugate vaccine (PCV7) followed by a 23-valent pneumococcal polysaccharide vaccine (PPSV23) failed to prevent new episodes of acute otitis media (AOM) in previously unvaccinated toddlers and children with a history of recurrent AOM. We describe in detail the impact of pneumococcal vaccinations on nasopharyngeal carriage of S. pneumoniae in this study population. METHODS The impact of vaccination with PCV7 followed by PPSV23 on pneumococcal nasopharyngeal carriage was studied in a prospective, randomized trial involving 383 children (age range, 1-7 years) with previous AOM. Nasopharyngeal swab specimens were collected at the time of first vaccination and at 6-7-month intervals during the 26-month follow-up period. RESULTS Overall, pneumococcal carriage rates did not diminish, remaining at approximately 50% in both PCV7/PPSV23 and control vaccinees. A significant shift from conjugate vaccine- to nonconjugate vaccine-type pneumococci was observed in children aged 1-2 years, who received the conjugate vaccine twice before the polysaccharide vaccine was administered. Conjugate vaccine serotype carriage was not influenced in older children, who received the conjugate vaccine once before receiving the polysaccharide booster. CONCLUSIONS The administration of conjugate vaccines at least twice also after 2 years of age may be mandatory for reducing the carriage of conjugate vaccine serotypes in children with recurrent AOM. Polysaccharide booster vaccination did not affect nasopharyngeal colonization with serotypes not included in the conjugate vaccine.

The effect of otitis media with effusion at preschool age on some aspects of auditory perception at school age

The relationship between otitis media with effusion (OME) at preschool age and performance on five tests of auditory perception was studied in 89 school-age children who had OME histories well documented from participation in serial screening for OME at 2-4 yr of age. The tests used at 7.5-8 yr of age were: speech-in-noise, filtered speech, binaural fusion, dichotic speech, and auditory memory. A significant effect of OME was found on the speech-in-noise test. No additional effects were demonstrated by this particular group of children.

Adenotonsillectomy for upper respiratory infections: Evidence based?

Background: Despite high rates of (adeno)tonsillectomy for upper respiratory infections in western countries, the medical literature offers the physician little support in deciding which child might benefit from the operation. Methods: A literature search was performed to identify randomised trials and non-randomised controlled studies into the efficacy of tonsillectomy with or without adenoidectomy in children under 18 years. For the outcomes sore throat episodes, sore throat associated school absence, and upper respiratory infections, pooled estimates of the incidence rate ratios and rate differences with 95% confidence intervals were calculated, assuming a Poisson distribution. Results: Six randomised trials and seven non-randomised controlled studies on the efficacy of adenotonsillectomy in children were evaluated. For sore throat episodes data for 2483 person-years were available. The pooled risk difference was −1.2 episodes per person-year (95% CI −1.3 to −1.1). For sore throat associated school absence 1669 person-years were analysed. The pooled risk difference was −2.8 days per person-year (95% CI −3.9 to −1.6). For upper respiratory infections 1596 person-years were available. The pooled risk difference was −0.5 episodes per person-year (95% CI −0.7 to −0.3). Conclusions: All available randomised trials and non-randomised controlled studies into the efficacy of (adeno)tonsillectomy had important limitations. The frequency of sore throat episodes and upper respiratory infections reduces with time whether (adeno)tonsillectomy has been performed or not. (Adeno)tonsillectomy gives an additional, but small, reduction of sore throat episodes, days of sore throat associated school absence, and upper respiratory infections compared to watchful waiting

Eustachian tube dysfunction: consensus statement on definition, types, clinical presentation and diagnosis.

A recent systematic review of treatments of Eustachian tube dysfunction commissioned by the UK NIHR Health Technology Assessment (HTA) Programme revealed that an important limitation with the available evidence is a lack of consensus on the definition and diagnosis of this disorder.1 The HTA report recommended that key to advancing research in this field is achieving consensus on diagnostic criteria for Eustachian tube dysfunction (to identify eligible patients for future trials) and on important clinical outcomes. To address this need, an international forum of scientists and physicians with expertise in the field of Eustachian tube disorders met at a workshop in Amsterdam on 21 June 2014 and was tasked to come to an agreement on the definition, clinical presentation and diagnosis of Eustachian tube dysfunction, and areas for future research. This study summarises the outcomes of that meeting.

The impact of recurrent acute otitis media on the quality of life of children and their caregivers

Objective:  To assess the quality of life of 384 Dutch children aged 1–7 years with recurrent acute otitis media (AOM), and compare it with that of children from four reference populations: (i) children from a general population; (ii) children with mild‐to‐moderate asthma, (iii) children with mild‐to‐moderately severe chronic illness, and (iv) US children with persistent or recurrent otitis media.

Immunoglobulins in Otitis-Prone Children

Defective or immature antibody responses to pathogens in children may explain the increased susceptibility to acute otitis media (AOM) in otitis-prone children. In literature, data on immunology have been based on studies of small groups of severely otitis-prone children and have not been consistent. Humoral immune status was assessed in 365 children, 1–7 years old, with two or more documented episodes of AOM in the previous year. Children with 4 or more episodes in the preceding year were defined as otitis-prone. Serum immunoglobulin levels were determined by radial immunodiffusion. Immunoglobulin levels of otitis-prone children were compared with those of children who had experienced 2-3 AOM episodes per year. Children with recurrent episodes of AOM were found to have normal or increased serum IgA, IgM, IgG, and IgG1 levels compared with normal values for age, whereas the serum IgG2 levels were mostly in the lower normal range. Twenty-two percent of all children showed IgG2 levels lower than 2 SD below the age-specific mean. Interestingly, the otitis-prone group of children showed significantly lower median and mean levels for all immunoglobulins compared with those children with only 2-3 previous AOM episodes. Lower immunoglobulin levels in otitis-prone children suggest a generalized decreased antibody response in otitis-prone children.