Biobanking for epidemiology.

Biobanks are a key resource in unravelling the association between genetic background, lifestyle and environmental determinants of the incidence, natural course and treatment response for various complex diseases and health traits. Biobanks are goldmines for epidemiological research, provided that they are set up properly, enable multicentre collaboration, and are available for use by all serious epidemiology groups.

A multi-faceted strategy to improve the use of national fertility guidelines; a cluster-randomized controlled trial.

BACKGROUND Proper use of clinical practice guidelines can decrease variation in care between settings. However, actual use of fertility guidelines is suboptimal and in need of improvement. Hence, a cluster-randomized controlled trial was designed to study the effects of two strategies to implement national Dutch guidelines on comprehensive fertility care. METHODS Sixteen fertility clinics participated in the trial. A minimal, professional-oriented implementation strategy of audit and feedback was tested versus a maximal multi-faceted strategy that was both professional and patient oriented. The extent of adherence to guideline recommendations, reflected in quality indicator scores, was the primary outcome measure. To gain an insight into unwanted side effects, patient anxiety and depression scores were gathered as secondary outcomes. Data collection encompassed medical record search, patient and professional questionnaires. RESULTS A total of 1499 couples were included at baseline and 1396 at the after-measurement. No overall significant improvement in indicator scores was found for either strategy [odds ratios ranging from 0.23 (95% confidence interval (CI): 0.06-0.95) to 6.66 (95% CI: 0.33-132.8]. Secondary outcomes did not differ significantly for both groups, although selected anxiety scores appeared lower in the maximal intervention group. Process evaluation of the trial revealed positive patient experiences with the intervention material [e.g. an increased understanding of their doctor's treatment policy (61%), an increased ability to ask questions about the treatment (61%)]. Professionals' appreciation of intervention elements varied, and execution of the multi-faceted strategy appeared incomplete. DISCUSSION Absence of an intervention effect may be due to the nature of the strategies, incomplete execution or flaws in study design. Process evaluation data raise the question of whether professionals should be the only stakeholder responsible for guideline implementation. This study therefore contributes to an increased understanding of fertility guideline implementation in general, and the role of patients in particular.

Antihypertensive treatment during pregnancy and functional development at primary school age in a historical cohort study.

OBJECTIVE: To determine the functional development of children born after treatment of mild-to-moderate gestational hypertension with labetalol versus methyldopa, and no antihypertensive treatment. DESIGN: Historical cohort study. SETTING: Twelve Dutch hospital departments of obstetrics. POPULATION: Live-born children born in these hospitals and prenatally exposed to labetalol, methyldopa, or bed rest because of mild-to-moderate gestational hypertension. METHODS: Central nervous system development was measured with standard tests at 4-10 years of age. Linear regression techniques and Pearson's chi-square tests were used to compare the groups with regard to the outcome measures. MAIN OUTCOME MEASURES: Intelligence quotient (IQ), concentration, motor development, and behaviour at primary school age. RESULTS: A total of 202 children were included in the analyses. More children exposed to labetalol had attention deficit hyperactivity disorder (ADHD) than those exposed to methyldopa (OR 2.3; 95% CI 0.7-7.3), or those born to women who had been admitted for bed rest (OR 4.1; 95% CI 1.2-13.9). Sleeping problems seemed to be reported more frequently after prenatal methyldopa exposure than after exposure to labetalol (OR 3.2; 95% CI 0.6-16.7) or bed rest (OR 4.5; 95% CI 0.9-23.2), although the differences were not statistically significant. Test scores on other aspects of functional development did not differ between the three groups. CONCLUSIONS: In this hypothesis-generating study, labetalol exposure in utero seemed to increase the risk of ADHD among children of primary school age, whereas prenatal methyldopa exposure might influence sleep. Further studies with appropriate sample sizes are warranted to determine the long-term effects of antihypertensive medications.

Variation in subfertility care measured by guideline-based performance indicators.

BACKGROUND: About 30-40% of patients do not receive care based on available scientific evidence. For subfertility, this may imply unnecessary and expensive diagnostic tests and treatments. It is therefore important to identify gaps in performance by monitoring current subfertility care. A set of 39 guideline-based performance indicators was previously developed for this purpose. This study aimed to assess several quality criteria of the indicator-set and to use the set to assess current subfertility care. METHODS: A historic cohort study was performed in 16 Dutch subfertility clinics; 2698 couples were invited to participate. Indicator data were gathered by medical record extraction, and patient and professional questionnaires. Quality criteria for each indicator (measurability, reliability, applicability, improvement potential, discriminatory capacity, complexity and case-mix stability) were assessed. Current practice was measured as adherence to the separate indicators. RESULTS: One thousand four-hundred and ninety-nine (56%) couples participated. All indicators were measurable, but the results for the other quality criteria varied. In total, 14 of the 39 indicators scored <50% adherence. Variation in performance between the clinics was up to 100%. The highest median adherence (86%) is found within the guideline 'indications for IVF-treatment'. The lowest median adherence is found within the guideline 'initial assessment of fertility' (43%), followed closely by the guideline 'anovulation' (44%). CONCLUSIONS: This study shows the quality of the developed indicator-set for monitoring clinical subfertility care. A first assessment in the Netherlands reveals large variation between clinics and ample room for improvement of care.

Estimating morbidity rates from electronic medical records in general practice. Evaluation of a grouping system.

OBJECTIVES: In this study, we evaluated the internal validity of EPICON, an application for grouping ICPC-coded diagnoses from electronic medical records into episodes of care. These episodes are used to estimate morbidity rates in general practice. METHODS: Morbidity rates based on EPICON were compared to a gold standard; i.e. the rates from the second Dutch National Survey of General Practice. We calculated the deviation from the gold standard for 677 prevalence and 681 incidence rates, based on the full dataset. Additionally, we examined the effect of case-based reasoning within EPICON using a comparison to a simple, not case-based method (EPI-0). Finally, we used a split sample procedure to evaluate the performance of EPICON. RESULTS: Morbidity rates that are based on EPICON deviate only slightly from the gold standard and show no systematic bias. The effect of case-based reasoning within EPICON is evident. The addition of case-based reasoning to the grouping system reduced both systematic and random error. Although the morbidity rates that are based on the split sample procedure show no systematic bias, they do deviate more from the gold standard than morbidity rates for the full dataset. CONCLUSIONS: Results from this study indicate that the internal validity of EPICON is adequate. Assuming that the standard is gold, EPICON provides valid outcomes for this study population. EPICON seems useful for registries in general practice for the purpose of estimating morbidity rates.

Prognosis and vascular co-morbidity in dementia a historical cohort study in general practice.

BACKGROUND: Disease management of dementia in general practice (GP) is hampered by a lack of data on the prognosis of dementia. AIM: To gain more insight into the life expectancy of and the effects of cardiovascular and cerebrovascular co-morbidity in dementia patients in GP. DESIGN OF STUDY: Historical cohort. SETTING: 4 general practices in Nijmegen, The Netherlands. POPULATION: All patients in these practices participating in the Continuous Morbidity Registration (CMR). METHODS: The patient cohort was diagnosed with dementia between January 1st 1985 and December 31st 2002. The control cohort consisted of patients matched one-to-one with demented patients on age, sex, and socio-economic status. Cardiovascular and cerebrovascular co-morbidity was studied from 5 years before the diagnosis of dementia till the endpoints of data collection. RESULTS: 251 couples of patients and controls were formed (79 men, 172 women, mean age 81.4+/-7.0 years). The median life expectancy after diagnosis was 2.3 years for the dementia patients, and 3.7 years for the controls. Median time from diagnosis till nursing home placement was 1.4 years. Cerebrovascular and cardiovascular morbidity preceding dementia diagnosis decreased survival of cases with dementia with a relative risk of 1.54 (95%CI: 1.13-2.09) and in controls with a relative risk of 1.91 (95%CI: 1.48-2.46). Obesity was associated with a lower risk of dementia (RR=0.77 (95%-CI 0.63-0.94)). Hypertension and obesity diagnosed after the dementia diagnosis were significantly associated with an increase in survival. CONCLUSION: In general practice, the diagnosis of dementia is made at a late stage, when patients will continue to live at home only for a short time. Moreover, life expectancy at diagnosis is very limited and prognosis is furthermore negatively influenced by preceding cardio- and cerebrovascular co-morbidity.

Self-management education for patients with chronic obstructive pulmonary disease.

BACKGROUND: There is great interest in chronic obstructive pulmonary disease (COPD) and the associated large burden of disease. COPD is characterised by frequent day by day fluctuations, and repetitive clinical exacerbations are typical. Self-management is a term applied to educational programmes aimed at teaching skills needed to carry out medical regimens specific to the disease, guide health behaviour change, and provide emotional support for patients to control their disease and live functional lives. In COPD, the value of self-management education is not yet clear. The first Cochrane review about self-management was published in 2003. It was intended to shed light on the effectiveness of self-management programmes in COPD and the relative efficacy of their constitutive elements. No conclusions about the effectiveness of self-management could be drawn because of the large variation in outcome measures used in the limited number of included studies. This article describes the first update of this review. OBJECTIVES: The objective of this review was to assess the settings, methods and efficacy of COPD self-management education programmes on health outcomes and use of health care services. SEARCH STRATEGY: We searched the Cochrane Airways Group trial register, MEDLINE (January 1985 to January 2006), reference lists, and abstracts of medical conferences. SELECTION CRITERIA: Controlled trials (randomised and non-randomised) of self-management education in patients with COPD. Studies focusing mainly on pulmonary rehabilitation and studies without usual care as a control group were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. Investigators were contacted for additional information. MAIN RESULTS: The reviewers included 15 group comparisons drawn from 14 trials. They assessed a broad-spectrum of interventions and health outcomes with different follow-up times. Meta-analyses could often not appropriately be performed because of heterogeneity among studies. The studies showed a significant reduction in the probability of at least one hospital admission among patients receiving self-management education compared to those receiving usual care (OR 0.64; 95% CI (0.47 to 0.89)). This translates into a one year NNT ranging from 10 (6 to 35) for patients with a 51% risk of exacerbation, to an NNT of 24 (16 to 80) for patients with a 13% risk of exacerbation. On the disease specific SGRQ, differences reached statistical significance at the 5% level on the total score (WMD -2.58; 95% CI (-5.14 to -0.02)) and impact domain (WMD -2.83; 95% CI (-5.65 to -0.02)), but these difference did not reach the clinically relevant improvement of 4 points. A small but significant reduction was detected in dyspnoea measured with the BORG-scale (WMD -0.53; 95% CI (-0.96 to -0.10)). No significant effects were found either in number of exacerbations, emergency department visits, lung function, exercise capacity, and days lost from work. Inconclusive results were observed in doctor and nurse visits, on symptoms other than dyspnoea, the use of courses of oral corticosteroids and antibiotics, and the use of rescue medication. AUTHORS' CONCLUSIONS: It is likely that self-management education is associated with a reduction in hospital admissions with no indications for detrimental effects in other outcome parameters. This would in itself already be enough reason for recommending self-management education in COPD. However, because of heterogeneity in interventions, study populations, follow-up time, and outcome measures, data are still insufficient to formulate clear recommendations regarding the form and contents of self-management education programmes in COPD. There is an evident need for more large RCTs with a long-term follow-up, before more conclusions can be drawn.

Validation of sonotubometry in healthy adults.

BACKGROUND: Frequent active opening of the eustachian tube (ET) allows ventilation of the middle ear and equilibration of pressure changes. Active opening is accomplished by the contraction of the paratubal muscles during swallowing. Because a disturbance of the ventilatory function of the ET may contribute to the development of otitis media with effusion, it is important to investigate ET function. Sonotubometry can be used to detect whether the ET can open or not during swallowing acts. METHODS: We developed a sonotubometer to test ET ventilatory function in 36 healthy adults. The width of the test signal frequency was between 5500 and 8500 Hz (centre frequency of 7000 Hz) and the loudness was 95 dB. To test reproducibility, testing took place in two sessions of 10 swallowing acts each. RESULTS: Opening of the ET could be registered in 91.6 per cent of the subjects in at least one of the two measurements. The first and the second measurements were highly correlated, with a Spearman's coefficient of 0.907. CONCLUSION: We confirmed that there is generally a good ventilatory ET function in otologically healthy adults, although, in a few cases, ET opening was not registered. Furthermore, we confirmed that our sonometric test equipment had acceptable reproducibility. Sonotubometry is a promising method for assessing ventilatory ET function. Research is ongoing to test the discriminative power of sonotubometry in children with various otological conditions.

Association of CD14 promoter polymorphism with otitis media and pneumococcal vaccine responses.

Innate immunity is of particular importance for protection against infection during early life, when adaptive immune responses are immature. CD14 plays key roles in innate immunity, including in defense against pathogens associated with otitis media, a major pediatric health care issue. The T allele of the CD14 C-159T polymorphism has been associated with increased serum CD14 levels. Our objective was to investigate the hypothesis that the CD14 C-159T allele is protective against recurrent acute otitis media in children. The association between the CD14 promoter genotype and the number of acute otitis media episodes was evaluated both retrospectively and prospectively in a cohort of 300 children. Serotype-specific immunoglobulin G (IgG) antibody responses after pneumococcal vaccinations were examined according to CD14 genotype to compare immune responsiveness across genotypes. An age-dependent association was found: compared with that for CC homozygotes aged between 12 to 24 months, TT homozygotes had fewer episodes of acute otitis media (79 versus 41%, respectively; P = 0.004); this relationship was absent in older children. Additionally, TT homozygotes showed higher serotype-specific anti-pneumococcal IgG antibody levels. Our data suggest that genetic variation in CD14, a molecule at the interface of innate and adaptive immune responses, plays a key role in the defense against middle ear disease in childhood and in pneumococcal vaccine responsiveness. These findings are likely to be important to these and other immune-mediated outcomes in early life.

Adenoidectomy and/or tonsillectomy in childhood is not associated with atopic disease later in life.

OBJECTIVE: To investigate the association between adenoidectomy and/or tonsillectomy in childhood and asthma, allergic rhinitis (AR), and eczema in adolescence. METHODS: Longitudinal birth cohort study of 1328 members born in the city of Nijmegen. Information on ear-nose-throat surgery was documented at 2, 4, and 8 years of age. In 1055 cohort members the incidence of asthma, AR, and eczema at 21 years of age was determined using the International Study of Asthma and Allergic disease in Childhood Core Questionnaire. To analyse the association between adenoidectomy and/or tonsillectomy in childhood and asthma, AR, and eczema at age 21 years, relative risks (RR) were calculated. RESULTS: Six hundred and ninety-three (66%) members completed the questionnaire at age 21 years, of whom 104 (15%) had undergone adenoidectomy and/or tonsillectomy and 262 (38%) reported atopic disease. Children who underwent adenoidectomy and/or tonsillectomy before the age of 8 years were not more likely to develop asthma, AR, or eczema at the age of 21 years than children who did not; RR 0.93 (95% confidence limits (CL) 0.52-1.64), RR 0.94 (CL 0.68-1.30), and RR 1.00 (CL 0.59-1.68), respectively. CONCLUSIONS: Our data show no association between adenoidectomy and/or tonsillectomy in childhood and the incidence of atopic disease in young adults.

Recurrent childhood upper respiratory tract infections do not reduce the risk of adult atopic disease.

BACKGROUND: Children of large families and those attending day care are at increased risk of respiratory tract infections, which in turn may protect against the development of allergic disease. Longitudinal studies investigating these associations beyond childhood are, however, scarce. OBJECTIVE: To investigate the association between childhood recurrent upper respiratory tract infections (URTI) and asthma, allergic rhinitis (AR) and eczema in adulthood. METHODS: A birth cohort of 1055 members followed prospectively from the ages of 2 to 21 years. Detailed information on URTI between the ages of 2 and 4 years was collected at 3 monthly intervals in a standardized interview. At the age of 8 years, a parental questionnaire regarding URTI between the ages of 4 and 8 years was used. The incidence of asthma and atopic disease at the age of 21 years was determined using a standardized questionnaire. RESULTS: Of the original cohort, 693 (66%) members completed the questionnaire. Children who experienced recurrent URTI before the age of 2 years, between the ages of 2-4 years and between ages of 4 and 8 years were not less likely to have asthma at 21 years of age than children who did not experience recurrent URTI, relative risk (RR) 0.97 (95% confidence interval (CI) 0.65-1.46), RR 1.45 (CI 0.95-2.21) and RR 1.51 (CI 0.97-2.36), respectively. Neither were recurrent URTI associated with a decreased risk of AR, nor eczema at the age of 21 years. CONCLUSIONS: Recurrent URTI in childhood did not reduce the risk of atopic disease in young adulthood.

Natural course of tympanic membrane pathology related to otitis media and ventilation tubes between ages 8 and 18 years.

OBJECTIVE: To present the course of tympanic membrane pathology in childhood and young adulthood after otitis media (OM) in early life. STUDY DESIGN: Prospective follow-up study. SETTING: Community study of a birth cohort. PATIENTS: Three hundred fifty-eight subjects with a positive and negative history of OM (OM+ or OM-) or ventilation tube insertion (VT+ or VT-) derived from a birth cohort that had been followed-up from preschool to adult age. METHODS: Standardized otomicroscopic examination performed at ages 8 and 18 years. MAIN OUTCOME MEASURES: Tympanic membrane abnormalities (i.e., tympanosclerosis, atrophy, atelectasis and retraction pockets of the pars tensa, and retraction of the pars flaccida). RESULTS: At the age of 8 years, tympanic membrane pathology was highly prevalent in the both OM+ subcohorts (OM+VT+, 92% and OM+VT-, 46%), whereas in the OM- ears (11%), tympanic membrane abnormalities were rare. In the subsequent 10-year period, many tympanic membrane abnormalities disappeared spontaneously, although the prevalence of tympanosclerosis remained substantial in the OM+VT+ cohort. CONCLUSION: The natural course of most tympanic membrane pathology associated with OM in early life is favorable over time, suggesting an intrinsic repair capacity of the tympanic membrane. Tympanosclerosis, the most prevalent sequelae of OM and treatment with VT, however, shows little tendency of resolution.

Grommets in otitis media with effusion: an individual patient data meta-analysis.

AIMS: To identify subgroups of children with otitis media with effusion (OME) that might benefit more than others from treatment with ventilation tubes. METHODS: An individual patient data (IPD) meta-analysis on seven randomised controlled trials (n = 1234 children in all), focusing on interactions between treatment and baseline characteristics--hearing level (HL), history of acute otitis media, common colds, attending day-care, gender, age, socioeconomic status, siblings, season, passive smoking, and history of breast feeding. Outcome measures that could be studied were mean time spent with effusion (n = 557), mean hearing levels (n = 557 in studies that randomised children, and n = 180 in studies that randomised ears), and language development (n = 381). RESULTS: In the trials that treated both ears the only significant interaction was between day-care and surgery, occurring where mean hearing level was the outcome measure. None of the other baseline variables showed an interaction effect with treatment that would justify subgrouping. In the trials that treated only one ear, the baseline hearing level showed a significant but not pervasive interaction with treatment-that is, only with a cut-off of 25 dB HL. CONCLUSIONS: The effects of conventional ventilation tubes in children studied so far are small and limited in duration. Observation (watchful waiting) therefore seems to be an adequate management strategy for most children with OME. Ventilation tubes might be used in young children that grow up in an environment with a high infection load (for example, children attending day-care), or in older children with a hearing level of 25 dB HL or greater in both ears persisting for at least 12 weeks.

Ventilation tubes in infants increase the risk of otorrhoea and antibiotic usage.

1) PROBLEM/OBJECTIVE: The effect of ventilation tubes on acute otitis related symptoms (otorrhoea, earache, and fever) and on antibiotic usage was investigated in children with persistent otitis media with effusion, as part of a multicenter, randomised, controlled clinical trial. 2) METHODOLOGY: One hundred-eighty-seven children were randomly placed into either a watchful waiting group (WW group) (n = 94) or a group treated with ventilation tubes (VT group) (n = 93). Both groups were followed for 12 months. Data were collected from parental reports and from medical files kept by the attending ENT-surgeons. 3) RESULTS: There were significant differences in the reported frequency of otorrhoea (but not of earache or fever) between both groups during follow-up, i.e. children in the VT group had more episodes of otorrhoea than the children in the WW group (p < 0.003). As a consequence, children in the VT group had been prescribed antibiotics more often. 4) CONCLUSIONS: Young children treated with ventilation tubes due to persistent otitis media with effusion have a higher risk of developing otorrhoea because of the tubes, and they have a higher risk of needing treatment with antibiotics.

Effectiveness of ultrasound screening for developmental dysplasia of the hip.

OBJECTIVE: To determine the effectiveness of ultrasound screening for developmental dysplasia of the hip (DDH) after the neonatal period. DESIGN: Prospective cohort study. SETTING: Child health care centres. PARTICIPANTS: Infants attending the child health care centres. INTERVENTIONS: The intervention group (n = 5170) was screened by ultrasound at 1, 2, and 3 months of age. The control group (n = 2066) was screened by routine physical examination as part of the programme for child health surveillance at the child health care centres (CHC screening). For evaluation of the screening, the children in both the intervention and control group received an ultrasound examination after 6 months of age to detect any abnormality that might have been missed by the screening. RESULTS: The sensitivity of the ultrasound screening was 88.5%, and the referral rate 7.6%. As a result of the ultrasound screening, 4.6% of the children were treated. The sensitivity of the CHC screening was 76.4%, with a referral rate of 19.2%. The treatment rate was 2.7%. Of the treated children in the ultrasound screening group, 67% were referred before the age of 13 weeks, whereas in the CHC screening group only 29% were referred before this age. CONCLUSIONS: This study shows that ultrasound screening detects more children with DDH than CHC screening and that more of them are detected at an earlier age. To accomplish this, even fewer children have to be referred. However, even general ultrasound screening seems not to eradicate late cases of DDH. The higher treatment rate in the population screened by ultrasound may be a result of overtreatment.

Pneumococcal vaccines for preventing otitis media.

BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Long term effects of recurrent episodes of otitis media, rapid emergence of drug resistant bacteria associated with AOM worldwide and huge estimated direct and indirect annual costs associated with otitis media have emphasized the need for an effective vaccination program to prevent episodes of AOM. OBJECTIVES: The object of this review was to assess the effect of pneumococcal vaccination in preventing AOM in children up to 12 years of age. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 2, 2003) which contains the Cochrane Acute Respiratory Infection Group's specialised register (30th June 2003), MEDLINE (January 1966 to June 2003), EMBASE (January 1990 to June 2003) and reference lists of all studies and review articles retrieved. We also contacted two vaccine manufacturers and first or corresponding authors of some of the included studies. SELECTION CRITERIA: Randomised controlled clinical trials of pneumococcal vaccination with prevention of AOM as outcome in children aged 12 years or younger and a follow-up of at least six months after vaccination. DATA COLLECTION AND ANALYSIS: Five reviewers independently assessed trial quality and two reviewers extracted data. Two study authors were contacted. MAIN RESULTS: Eight trials on 8-to 14-valent pneumococcal polysaccharide vaccine (PPV) and four trials on 7-to 9-valent pneumococcal conjugate vaccine (PCV) were included. The highest efficacy of PPV was found in children aged 24 months and older: the rate ratio was 0.779 [95% CI: 0.625-0.970]. PPV has little effect on the prevention of AOM in children without documented prior episodes of AOM and only a moderate effect in the group of children with documented AOM episodes prior to vaccination. Pooled results of the four PCV trials in infants vaccinated as early as two months of age and toddlers attending daycare and toddlers with recurrent AOM showed only a small effect on prevention of AOM (rate ratio 0.921; 95% CI: 0.894-0.950). REVIEWER'S CONCLUSIONS: Based on the currently available results of the effectiveness of pneumococcal vaccination for the prevention of AOM, a large scale use of pneumococcal polysaccharide and conjugate vaccination for this specific indication is not yet recommended. So far, pneumococcal conjugate vaccinations are not indicated in the management of recurrent AOM in toddlers and older children. The results of currently ongoing trials of 9- and 11-valent conjugate vaccines should provide more information as to whether pneumococcal vaccines are more effective in specific high-risk populations like infants and older children with recurrent AOM or immunodeficiency.

The effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion at 7 and 24 months of age.

OBJECTIVE: To explore the effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion and to search for subgroups in which the vaccine had a higher or lower effect. METHODS: Analyses were performed on data from the Finnish Otitis Media Vaccine Trial, a randomised controlled double-blind trial to evaluate the efficacy of pneumococcal conjugate vaccination against acute otitis media. Data on the vaccination effect against otitis media with effusion were obtained by means of symptom interview and pneumatic otoscopy during pre-scheduled follow-up visits at the age of 7 and 24 months. Two endpoint definitions were considered: otitis media/tube (otitis media or tympanostomy tube in situ (OM/T)) as the primary endpoint and otitis media with effusion as the secondary endpoint. No evidence was found of an age-dependent association with vaccination effect. Therefore, the final marginal logistic regression analyses were performed on the combined data from the two follow-up visits. RESULTS: The risk of otitis media tended to be lower in the pneumococcal vaccine group. The odds ratio for otitis media/tube was 0.94 (95% confidence interval 0.77-1.14) and the odds ratio for otitis media with effusion was 0.90 (95% confidence interval 0.69-1.19). Presence of older siblings increased the risk of otitis media/tube and otitis media with effusion at 7 months of age. In addition, it appeared that children without older siblings and attending day-care at 24 months of age tended to benefit more from the pneumococcal conjugate vaccine. In this subgroup, the odds ratio for otitis media/tube was 0.81 (95% confidence interval 0.55-1.20) and for otitis media with effusion the odds ratio was 0.43 (95% confidence interval 0.22-0.86). CONCLUSION: The effect of pneumococcal conjugate vaccination on the risk of otitis media with effusion was concordant with the efficacy seen against acute otitis media, although not distinguishable from no effect in the overall analysis. In children without older siblings, vaccination appeared to reduce the point prevalence of otitis media with effusion; this effect was not apparent in children with older siblings.

Ultrasonographic screening for developmental dysplasia of the hip in infants. Reproducibility of assessments made by radiographers.

We studied the reproducibility of ultrasonographic screening examination of the hip when read by diagnostic radiographers. In order to determine interobserver variability, 200 ultrasonograms were classified according to Graf's method by five observers (four radiographers and one radiologist). The kappa values for interobserver variability indicated moderate agreement (kappa 0.47) for the exact Graf classification and substantial agreement (kappa 0.65) for the classification of normal (type I) versus abnormal (type IIa-IV). Agreement was significantly different for normal, immature and abnormal hips. Comparison of the findings in our interobserver study with existing information based on other examinations and treatment revealed that only a small number of infants with mildly dysplastic hips would have been typed as normal by some observers as a result of observer variability. In conclusion, the interobserver agreement on the ultrasound assessment of the hip was good enough for screening purposes. Observer variability did not result in any severe cases being missed.

Does a trial on the effects of ventilation tubes influence clinical practice?

A survey was performed to study the implementation of the results of a clinical trial on the effect of ventilation tubes on daily clinical practice. Two random samples of 75 Dutch otorhinolaryngologists each were drawn: one before the conduction of the trial and another after the results were disseminated. In both surveys participants were asked to give their personal estimate of the probability of complete recovery without treatment and after the insertion of ventilation tubes in an infant with bilateral otitis media with effusion. The trial showed no long lasting effects of ventilation tubes on hearing, language development and quality of life, yet, the overall expectation with respect to the effect of ventilation tubes remained high. The study suggests that the adoption of research results require more than simple dissemination of the results. (Inter)national debate is recommended to value the results of clinical trials for daily practice.

Self-management education for chronic obstructive pulmonary disease.

BACKGROUND: In asthma, self-management programmes have been proven to be effective. In COPD, their value is not clear. OBJECTIVES: To assess the efficacy of COPD self-management/ education programmes on health outcomes and use of health services SEARCH STRATEGY: We searched the Cochrane Airways Group trial registers, MEDLINE (January 1985 to October 2001), reference lists, and abstracts of medical conferences. We also contacted research groups in the field for ongoing trials and unpublished material. SELECTION CRITERIA: Controlled trials (randomised and non-randomised) of self-management education in patients with COPD. Studies focusing mainly on physical pulmonary rehabilitation were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Investigators were contacted for additional information. MAIN RESULTS: The reviewers included 12 articles describing 8 randomised-controlled trials and 1 controlled clinical trial. Self-management education was compared with usual care in 8 studies. The studies in this review assessed a broad-spectrum of outcome measures with different follow-up times. Synthesis of the results using meta-analysis was always not possible. The studies showed no effect of self-management education on hospital admissions, emergency room visits, days lost from work and lung function. Inconclusive results were observed on health-related quality of life (HRQoL): studies using the disease specific SGRQ showed a better quality of life in the patients in the intervention group, but only in the activity component where there was heterogeneity between the results of the two included studies. A potential reason for the absence of convincing effects on HRQoL is the limited use of COPD-specific instruments. Inconclusive results were observed on COPD-symptoms and use of other health care resources such as doctor and nurse visits. Self-management education reduced the need for rescue medication, and led to an increased use of courses of oral steroids and antibiotics for respiratory symptoms. REVIEWER'S CONCLUSIONS: The data available for this review are insufficient for forming recommendations. Further research on the effectiveness of self-management programmes should be focussed on behavioural change evaluated in well designed randomised controlled trials with standardised outcomes designed for use in COPD patients, and with long follow-up time so that definite conclusions can be made.