Recommendations for clinical research in children presenting to primary care out-of-hours services

BACKGROUND: Research in primary care is essential, but recruiting children in this setting can be complex and may cause selection bias. Challenges surrounding informed consent, particularly in an acute clinical setting, can undermine feasibility. The off-protocol use of an intervention nearing implementation has become common in pragmatic randomized controlled trials (RCTs) set in primary care. AIM: To describe how the informed consent procedure affects study inclusion and to assess how off-protocol medication prescribing affects participant selection in a paediatric RCT. DESIGN: A pragmatic RCT evaluating the cost-effectiveness of oral ondansetron in children diagnosed with acute gastroenteritis in primary care out-of-hours services and a parallel cohort study. METHOD: Consecutive children aged 6 months to 6 years attending primary care out-of-hours services with acute gastroenteritis were evaluated to assess the feasibility of obtaining informed consent, the off-protocol use of ondansetron, and other inclusion/exclusion criteria. RESULTS: The RCTs feasibility was reduced by the informed consent procedure because 39.0% (325/834) of children were accompanied by only one parent. General practitioners prescribed ondansetron off-protocol to 34 children (4.1%), whereof 19 children were eligible for the RCT. RCT-eligible children included in the parallel cohort had fewer risk factors for dehydration than children in the RCT despite similar dehydration assessments by general practitioners. CONCLUSION: The informed consent procedure and off-protocol use of study medication affect the inclusion rate but had little effect on selection. A parallel cohort study alongside the RCT can help evaluate selection bias, and a pilot study can reveal potential barriers to inclusion

Oral ondansetron for paediatric gastroenteritis in primary care:a randomised controlled trial

BACKGROUND: Acute gastroenteritis (AGE) affects almost all children aged ≤5 years. In secondary care, ondansetron was found to be effective at reducing vomiting. AIM: To determine the effectiveness of adding oral ondansetron to care as usual (CAU) to treat vomiting in children with AGE attending out-ofhours primary care (OOH-PC). DESIGN AND SETTING: A pragmatic randomised controlled trial at three OOH-PC centres in the north of the Netherlands (Groningen, Zwolle, and Assen), with a follow-up of 7 days. METHOD: Children were included if they were: aged 6 months–6 years; AGE diagnosed by a GP; ≥4 reported episodes of vomiting in the 24 hours before presentation; ≥1 reported episode of vomiting in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated to either the control group or the intervention group. The control group received CAU, namely oral rehydration therapy. The intervention group received CAU plus one dose of oral ondansetron (0.1 mg/kg). RESULTS: In total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within 4 hours from 42.9% to 19.5%, with an odds ratio of 0.37 (95% confidence interval [CI] = 0.20 to 0.72, number needed to treat: four). Ondansetron also decreased the number of vomiting episodes within 4 hours (incidence rate ratio 0.51 [95% CI = 0.29 to 0.88]) and improved overall parental satisfaction with treatment (P = 0.027). CONCLUSION: Children with AGE and increased risk of dehydration due to vomiting could be treated with ondansetron in primary care to stop vomiting more quickly and increase parental satisfaction with treatment. These results could be used to improve the quality and efficacy of general practice medicine

Role of Systemic Factors in Improving the Prognosis of Diabetic Retinal Disease and Predicting Response to Diabetic Retinopathy Treatment

TOPIC: To review clinical evidence on systemic factors that might be relevant to update diabetic retinal disease (DRD) staging systems, including prediction of DRD onset, progression, and response to treatment.CLINICAL RELEVANCE: Systemic factors may improve new staging systems for DRD to better assess risk of disease worsening and predict response to therapy.METHODS: The Systemic Health Working Group of the Mary Tyler Moore Vision Initiative reviewed systemic factors individually and in multivariate models for prediction of DRD onset or progression (i.e., prognosis) or response to treatments (prediction).RESULTS: There was consistent evidence for associations of longer diabetes duration, higher glycosylated hemoglobin (HbA1c), and male sex with DRD onset and progression. There is strong trial evidence for the effect of reducing HbA1c and reducing DRD progression. There is strong evidence that higher blood pressure (BP) is a risk factor for DRD incidence and for progression. Pregnancy has been consistently reported to be associated with worsening of DRD but recent studies reflecting modern care standards are lacking. In studies examining multivariate prognostic models of DRD onset, HbA1c and diabetes duration were consistently retained as significant predictors of DRD onset. There was evidence of associations of BP and sex with DRD onset. In multivariate prognostic models examining DRD progression, retinal measures were consistently found to be a significant predictor of DRD with little evidence of any useful marginal increment in prognostic information with the inclusion of systemic risk factor data apart from retinal image data in multivariate models. For predicting the impact of treatment, although there are small studies that quantify prognostic information based on imaging data alone or systemic factors alone, there are currently no large studies that quantify marginal prognostic information within a multivariate model, including both imaging and systemic factors.CONCLUSION: With standard imaging techniques and ways of processing images rapidly evolving, an international network of centers is needed to routinely capture systemic health factors simultaneously to retinal images so that gains in prediction increment may be precisely quantified to determine the usefulness of various health factors in the prognosis of DRD and prediction of response to treatment.FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p

Invasive Haemophilus influenzae Disease, Europe, 1996–2006

Incidence and case-fatality ratios are higher for non–type b than for type b infection

Lipid-coated polymeric nanoparticles for cancer drug delivery

Polymeric nanoparticles and liposomes have been the platform of choice for nanoparticle-based cancer drug delivery applications over the past decade, but extensive research has revealed their limitations as drug delivery carriers. A hybrid class of nanoparticles, aimed at combining the advantages of both polymeric nanoparticles and liposomes, has received attention in recent years. These core/shell type nanoparticles, frequently referred to as lipid–polymer hybrid nanoparticles (LPNs), possess several characteristics that make them highly suitable for drug delivery. This review introduces the formulation methods used to synthesize LPNs and discusses the strategies used to treat cancer, such as by targeting the tumor microenvironment or vasculature. Finally, it discusses the challenges that must be overcome to realize the full potential of LPNs in the clinic

Spielt Pseudomonas aeruginosa eine therapierelevante Rolle bei der akuten Mastoiditis?

Einleitung: Die akute Mastoiditis, die eitrige Entzündung des Warzenfortsatzes mit knöcherner Einschmelzung meist als Komplikation einer akuten Otitis media, ist eine zwar insgesamt seltene, aber gefährliche Erkrankung. Oft wird in der Literatur Pseudomonas aeruginosa als ein wichtiger Erreger genannt.Material und Methoden: Von 1999 bis 2004 wurden in der HNO-Klinik unseres Universitätsklinikums 43 intraoperative Abstiche von 41 Patienten mit einer akuten Mastoiditis gewonnen.Ergebnisse: Aus den 43 Abstrichen konnten insgesamt 35 Erreger isoliert werden. Bei 27 Patienten wurde ein Erreger und bei 4 Patienten wurden 2 Erreger angezüchtet. 12 Materialien waren steril.Streptococcus pneumoniae war mit 57% der absolute Haupterreger, es folgten mit 20% die A-Streptokokken. Staphylococcus aureus 8% und andere grampositive Erreger (11%) folgten mit deutlichem Abstand. Pseudomonas aeruginosa wurde nur bei einem Patienten nach Parazentese aus dem Gehörgang nachgewiesen, jedoch wurde bei dem gleichen Patienten Streptococcus pneumoniae aus dem Mastoid angezüchtet.Schlussfolgerung: Haupterreger der akuten Mastoiditis sind die grampositiven Kokken, vor allem Pneumokokken und A-Streptokokken. Pseudomonaden spielen keine therapierelevante Rolle. Die Ergebnisse von Gehörgangsabstrichen sind nicht verwertbar

Identification of biomarkers for diabetic retinopathy

In this thesis Ward Fickweiler identified certain protective factors that help prevent diabetic eye disease from developing in some individuals with type 1 diabetes. One protein, known as retinol binding protein 3, was shown to protect both the neuroretina and vascular retina from diabetes-induced disease. Also we found that common protective factors between diabetic eye disease and cardiovascular disease may exist. We also examined a potential new pathway in the development of diabetic eye disease, the kallikrein kinin system. Lastly, we evaluated the usefulness of non-invasive imaging techniques and peripheral blood compounds to predict treatment response in diabetic eye disease. We found several characteristics on retinal imaging and peripheral blood compounds that may be helpful in predicting treatment response in diabetic eye disease

The Acceptance of Wrinkles: Ageing in Kazuo Ishiguro's Novels

In this dissertation I discuss the role of ageing in Kazuo Ishiguro's An Artist of the Floating World (1986), The Remains of the Day (1989) and Never Let Me Go (2005). Although the three novels appear rather different in their themes and setting, they are comparable in their portrayal of the development of the attitude towards ageing, or impending death, which is greatly influenced by Japanese culture.