The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no ‘gold standard’ reference test. Hence, a task force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in the light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on: clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of PCD; also to provide advice when the diagnosis is not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for PCD.

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Objective To provide an overview of drug use in children in three European countries.Design Retrospective cohort study, 2000-5.Setting Primary care research databases in the Netherlands (IPCI), United Kingdom (IMS-DA), and Italy (Pedianet).Participants 675 868 children aged up to 14 (Italy) or 18 (UK and Netherlands).Main outcome measure Prevalence of use per year calculated by drug class (anatomical and therapeutic). Prevalence of “recurrent/chronic” use (three or more prescriptions a year) and “non-recurrent” or “acute” use (less than three prescriptions a year) within each therapeutic class. Descriptions of the top five most commonly used drugs evaluated for off label status within each anatomical class.Results Three levels of drug use could be distinguished in the study population: high (>10/100 children per year), moderate (1-10/100 children per year), and low (<1/100 children per year). For all age categories, anti-infective, dermatological, and respiratory drugs were in the high use group, whereas cardiovascular and antineoplastic drugs were always in the low use group. Emollients, topical steroids, and asthma drugs had the highest prevalence of recurrent use, but relative use of low prevalence drugs was more often recurrent than acute. In the top five highest prevalence drugs topical inhaled and systemic steroids, oral contraceptives, and topical or systemic antifungal drugs were most commonly used off label.Conclusion This overview of outpatient paediatric prescription patterns in a large European population could provide information to prioritise paediatric therapeutic research needs.

BackgroundSmall clinical trials are necessary when there are difficulties in recruiting enough patients for conventional frequentist statistical analyses to provide an appropriate answer. These trials are often necessary for the study of rare diseases as well as specific study populations e.g. children. It has been estimated that there are between 6,000 and 8,000 rare diseases that cover a broad range of diseases and patients. In the European Union these diseases affect up to 30 million people, with about 50% of those affected being children. Therapies for treating these rare diseases need their efficacy and safety evaluated but due to the small number of potential trial participants, a standard randomised controlled trial is often not feasible. There are a number of alternative trial designs to the usual parallel group design, each of which offers specific advantages, but they also have specific limitations. Thus the choice of the most appropriate design is not simple.MethodsPubMed was searched to identify publications about the characteristics of different trial designs that can be used in randomised, comparative small clinical trials. In addition, the contents tables from 11 journals were hand-searched. An algorithm was developed using decision nodes based on the characteristics of the identified trial designs.ResultsWe identified 75 publications that reported the characteristics of 12 randomised, comparative trial designs that can be used in for the evaluation of therapies in orphan diseases. The main characteristics and the advantages and limitations of these designs were summarised and used to develop an algorithm that may be used to help select an appropriate design for a given clinical situation. We used examples from publications of given disease-treatment-outcome situations, in which the investigators had used a particular trial design, to illustrate the use of the algorithm for the identification of possible alternative designs.ConclusionsThe algorithm that we propose could be a useful tool for the choice of an appropriate trial design in the development of orphan drugs for a given disease-treatment-outcome situation.

We identified different risk factors for specific childhood wheezing phenotypes. Some of these are modifiable, such as maternal age and body mass index, smoking, day-care attendance and breastfeeding, and may be important targets for prevention programmes.

Rationale For clinicians it remains very difficult to predict whether preschool children with symptoms suggestive of asthma will develop asthma in later childhood. Objective To investigate whether measurement of fraction of exhaled nitric oxide (FE NO ), interrupter resistance (Rint) or specific immunoglobulin E (IgE) in 4-year-old children with suggestive symptoms can predict asthma symptoms up to age 8 years. Methods Children were recruited from the PIAMA birth cohort. All children with symptoms suggestive of asthma at age 3 or 4 years, who were invited for medical examination at age 4 (n¼848), were eligible. Associations of FE NO (n¼308), Rint (n¼482) and specific IgE (n¼380) at 4 years with wheezing and asthma at the ages of 5e8 years were assessed using repeated measurement analyses. The added predictive value of these objective tests was then investigated by including parameters for clinical history in the model.