Risks for comorbidity in children with atopic disorders: an observational study in Dutch general practices

OBJECTIVE: This study aimed to investigate both atopic and non-atopic comorbid symptoms and diseases in children with physician-diagnosed atopic disorders (atopic eczema, asthma and allergic rhinitis).METHODS: All children aged 0-18 years listed in a nationwide primary care database (the Netherlands Institute for Health Services Research-Primary Care Database) with routinely collected healthcare data in 2014 were selected. Children with atopic disorders were matched on age and gender with non-atopic controls within the same general practice. A total of 404 International Classification of Primary Care codes were examined. Logistic regression analyses were performed to examine the associations between the presence of atopic disorders and (non-)atopic symptoms and diseases by calculating ORs.RESULTS: Having one of the atopic disorders significantly increased the risk of having other atopic-related symptoms, even if the child was not registered as having the related atopic disorder. Regarding non-atopic comorbidity, children with atopic eczema (n=15 530) were at significantly increased risk for (infectious) skin diseases (OR: 1.2-3.4). Airway symptoms or (infectious) diseases (OR: 2.1-10.3) were observed significantly more frequently in children with asthma (n=7887). Children with allergic rhinitis (n=6835) had a significantly distinctive risk of ear-nose-throat-related symptoms and diseases (OR: 1.5-3.9). Neither age nor gender explained these increased risks.CONCLUSION: General practitioners are not always fully aware of relevant atopic and non-atopic comorbidity. In children known to have at least one atopic disorder, specific attention is required to avoid possible insufficient treatment and unnecessary loss of quality of life

A young child with a history of wheeze

The parents of a 3-year old boy are anxious about their son who has recurring episodes of wheezing. They are frustrated that no one seems to be able to give them answers to their questions and would like a referral to a specialist. Does their son have asthma and what is the prognosis; how can the recurrent wheezing be managed and can the risk of asthma be reduced; are there lifestyle changes that could improve the environment and avoid triggers? Communication and support from the family practice team were essential. Listening to the parents' concerns, explaining the diagnostic uncertainty, being realistic about what drug treatments could achieve, and providing practical advice on inhaler use and trigger avoidance reassured the parents that there was a strategy for managing their son's wheeze. The specialist referral was postponed

The effect of two lottery-style incentives on response rates to postal questionnaires in a prospective cohort study in preschool children at high risk of asthma: A randomized trial

Background: In research with long-term follow-up and repeated measurements, quick and complete response to questionnaires helps ensure a study's validity, precision and efficiency. Evidence on the effect of non-monetary incentives on response rates in observational longitudinal research is scarce. Objectives. To study the impact of two strategies to enhance completeness and efficiency in observational cohort studies with follow-up durations of around 2 years. Method and intervention. In a factorial design, 771 children between 2 and 5 years old and their parents participating in a prospective cohort study were randomized to three intervention groups and a control group. Three types of lotteries were run: (i) daytrip tickets for the whole family to a popular amusement park if they returned all postal questionnaires, (ii) 12.50-worth gift vouchers for sending back the questionnaire on time after each questionnaire round and (iii) a combination of (i) and (ii). Main outcome measures. Primary outcome was the proportion of participants who returned all questionnaires without any reminder. Secondary outcomes were '100% returned with or without reminder', 'probability of 100% non-response', 'probability of withdrawal', 'proportion of returned questionnaires' and 'overall number of reminders sent'. Statistical analysis. After testing for interaction between the two lottery interventions, the two trials were analysed separately. We calculated risk differences (RD) and numbers needed to "treat" and their 95% confidence intervals. Results: Daytrip nor voucher intervention had an effect on the proportion of participants who returned all questionnaires (RD -0.01; 95% CI-0.07 - 0.06) and (RD 0.02; 95% CI-0.50 - 0.08), respectively. No effects were found on the secondary outcomes. Conclusion: Our findings do not support the idea that lottery-style incentives lead to more complete response to postal questionnaires in observational cohort studies with repeated data collection and follow-up durations of around 2 years

Interrelationships between atopic disorders in children

Purpose To study the prevalence and interrelationship between asthma, allergic rhinitis and eczema using data obtained from ISAAC questionnaires. Method The Medline, Pubmed Publisher, EMBASE, Google Scholar and the Cochrane Controlled Clinical Trials Register databases were systematically reviewed to evaluate epidemiological data of children with atopic disorders. To study these interrelationships, a new approach was used. Risk ratios were calculated, describing the risk of having two different atopic disorders when the child is known with one disorder. Results Included were 31 studies, covering a large number of surveyed children (n=1,430,329) in 102 countries. The calculated worldwide prevalence for asthma, eczema and allergic rhinitis is 12.00% (95% CI: 11.99-12.00), 7.88% (95% CI: 7.88-7.89) and 12.66% (95% CI: 12.65-12.67), respectively. The observed prevalence [1.17% (95% CI: 1.17-1.17)] of having all three diseases is 9.8 times higher than could be expected by chance. For children with asthma the calculated risk ratio of having the other two disorders is 5.41 (95% CI: 4.76-6.16), for children with eczema 4.24 (95% CI: 3.75-4.79), and for children with allergic rhinitis 6.20 (95% CI: 5.30-7.27). No studied confounders had a significant influence on these risk ratios. Conclusions Only a minority of children suffers from all three atopic disorders, however this co-occurrence is significantly higher than could be expected by chance and supports a close relationship of these disorders in children. The data of this meta-analysis supports the hypothesis that there could be a fourth distinct group of children with all three disorders. Researchers and clinicians might need to consider these children as a separate group with distinct characteristics regarding severity, causes, treatment or prognosis

Predicting asthma in preschool children at high risk presenting in primary care: Development of a clinical asthma prediction score

Background: A setting-specific asthma prediction score for preschool children with wheezing and/or dyspnoea presenting in primary healthcare is needed since existing indices are mainly based on general populations. Aims: To find an optimally informative yet practical set of predictors for the prediction of asthma in preschool children at high risk who present in primary healthcare. Methods: A total of 771 Dutch preschool children at high risk of asthma were followed prospectively until the age of six years. Data on asthma symptoms and environmental conditions were obtained using validated questionnaires and specific IgE was measured. At the age of six years the presence of asthma was assessed based on asthma symptoms, medication, and bronchial hyper-responsiveness. A clinical asthma prediction score (CAPS) was developed using bootstrapped multivariable regression methods. Results: In all, 438 children (56.8%) completed the study; the asthma prevalence at six years was 42.7%. Five parameters optimally predicted asthma: age, family history of asthma or allergy, wheezing-induced sleep disturbances, wheezing in the absence of common colds, and specific IgE. CAPS scores range from 0 to 11 points; scores <3 signified a negative predictive value of 78.4% while scores of ≥7 signified a positive predictive value of 74.3%. Conclusions: We have developed an easy-to-use CAPS for preschool children with symptoms suggesting asthma who present in primary healthcare. After suitable validation, the CAPS may assist in guiding shared decision-making to tailor the need for medical or non-medical interventions. External validation of the CAPS is needed

Defining hip pain trajectories in early symptomatic hip osteoarthritis - 5 year results from a nationwide prospective cohort study (CHECK)

Objective: To define distinct hip pain trajectories in individuals with early symptomatic hip osteoarthritis (OA) and to determine risk factors for these pain trajectories. Method: Data were obtained from the nationwide prospective Cohort Hip and Cohort Knee (CHECK) study. Participants with hip pain or stiffness and a completed 5-year follow-up were included. Baseline demographic, anamnestic, physical examination characteristics were assessed. Outcome was annually assessed by the Numeric Rating Scale (NRS) for pain. Pain trajectories were retrieved by latent class growth analysis (LCGA). Multinomial logistic regression was used to calculate risk ratios. Results: 545 participants were included. Four distinct pain trajectories were uncovered by LCGA. We found significant differences in baseline characteristics, including body mass index (BMI); symptom severity; pain coping strategies and in criteria for clinical hip OA (American College of Rheumatology (ACR)). Lower education, higher activity limitation scores, frequent use of pain transformation as coping strategy and painful internal hip rotation were more often associated with trajectories characterized by more severe pain. No association was found for baseline radiographic features. Conclusion: We defined four distinct pain trajectories over 5 years follow-up in individuals with early symptomatic hip OA, suggesting there are differences in symptomatic progression of hip OA. Baseline radiographic severity was not associated with the pain trajectories. Future research should be aimed at measuring symptomatic progression of hip OA with even more frequent symptom assessment

Reliably estimating prevalences of atopic children: An epidemiological study in an extensive and representative primary care database

Electronic health records stored in primary care databases might be a valuable source to study the epidemiology of atopic disorders and their impact on health-care systems and costs. However, the prevalence of atopic disorders in such databases varies considerably and needs to be addressed. For this study, all children aged 0-18 years listed in a representative primary care database in the period 2002-2014, with sufficient data quality, were selected. The effects of four different strategies on the prevalences of atopic disorders were examined: (1) the first strategy examined the diagnosis as recorded in the electronic health records, whereas the (2) second used additional requirements (i.e., the patient had at least two relevant consultations and at least two relevant prescriptions). Strategies (3) and (4) assumed the atopic disorders to be chronic based on strategy 1 and 2, respectively. When interested in cases with a higher probability of a clinically relevant disorder, strategy 2 yields a realistic estimation of the prevalence of atopic disorders derived from primary care data. Using this strategy, of the 478,076 included children, 28,946 (6.1%) had eczema, 29,182 (6.1%) had asthma, and 28,064 (5.9%) had allergic rhinitis; only 1251 (0.3%) children had all three atopic disorders. Prevalence rates are highly dependent on the clinical atopic definitions used. The strategy using cases with a higher probability of clinically relevant cases, yields realistic prevalences to establish the impact of atopic disorders on health-care systems. However, studies are needed to solve the problem of identifying atopic disorders that are missed or misclassified

A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four

Background: The recommendations for the treatment of moderate persistent asthma in the Global Initiative for Asthma (GINA) guidelines for paediatric asthma are mainly based on scientific evidence extrapolated from studies in adults or on consensus. Furthermore, clinical decision-making would benefit from formal ranking of treatments in terms of effectiveness.Our objective is to assess all randomized trial-based evidence specifically pertaining to 5-18 year olds with moderate persistent asthma. Rank the different drug treatments of GINA guideline steps 3&4 in terms of effectiveness.Methods: Systematic review with network meta-analysis. After a comprehensive search in Central, Medline, Embase, CINAHL and the WHO search portal two reviewers selected RCTs performed in 4,129 children from 5-18 year old, with moderate persistent asthma comparing any GINA step 3&4 medication options. Further quality was assessed according the Cochrane Collaboration's tool and data-extracted included papers and built a network of the trials. Attempt at ranking treatments with formal statistical methods employing direct and indirect (e.g. through placebo) connections between all treatments.Results: 8,175 references were screened; 23 randomized trials (RCT), comparing head-to-head (n=17) or against placebo (n=10), met the inclusion criteria. Except for theophylline as add-on therapy in step 4, a closed network allowed all comparisons to be made, either directly or indirectly. Huge variation in, and incomplete reporting of, outcome measurements across RCTs precluded assessment of relative efficacies.Conclusion: Evidence-based ranking of effectiveness of drug treatments in GINA steps 3&4 is not possible yet. Existing initiatives for harmonization of outcome measurements in asthma trials need urgent implementation

Adverse drug reactions in a primary care population prescribed non-steroidal anti-inflammatory drugs

Objective. To determine how often patients with musculoskeletal (MSK) complaints prescribed a non-steroidal anti-inflammatory drug (NSAID) subsequently consult their general practitioner (GP) with a non-serious adverse drug reaction (ADR). Design. Cohort study. Setting. A healthcare database containing the electronic GP medical records of over 1.5 million patients throughout the Netherlands. Patients. A total of 16 626 adult patients with MSK complaints prescribed an NSAID. Main outcome measures. The patients' medical records were manually assessed for the duration of NSAID use for a maximum of two months, and consultations for complaints predefined as potential ADRs were identified. Subsequently, the likelihood of an association with the NSAID use was assessed and these potential ADRs were categorized as likely, possible, or unlikely ADRs. Results. In total, 961 patients (6%) consulted their GP with 1227 non-serious potential ADRs. In 174 patients (1%) at least one of these was categorized as a likely ADR, and in a further 408 patients (2.5%) at least one was categorized as a possible ADR. Dyspepsia was the most frequent likely ADR, followed by diarrhoea and dyspnoea (respectively 34%, 8%, and 8% of all likely ADRs). Conclusion. Of the patients with MSK complaints prescribed an NSAID, almost one in 30 patients re-consulted their GP with a complaint likely or possibly associated with the use of this drug. The burden of such consultations for non-serious ADRs should be taken into account by GPs when deciding whether treatment with an NSAID is appropriate