Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series

OBJECTIVE: To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Design: Randomised, double blind, placebo controlled, parallel group, multicentre study. SETTING: Four general practices and a hospital ear, nose, and throat outpatient department. PARTICIPANTS: 51 patients with perennial allergic rhinitis. Intervention: Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. MAIN OUTCOME MEASURES: Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. RESULTS: Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). CONCLUSION: The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo

A Comparative Study of the Magnitude, Frequency and Distribution of Intense Rainfall in the United Kingdom

During the 1960s, a study was made of the magnitude, frequency and distribution of intense rainfall over the UK, employing data from more than 120 daily-read rain gauges covering the period 1911 to 1960. Using the same methodology, that study was recently updated utilizing data for the period 1961 to 2006 for the same gauges, or from those nearby. This paper describes the techniques applied to ensure consistency of data and statistical modelling. It presents a comparison of patterns of extreme rainfalls for the two periods and discusses the changes that have taken place. Most noticeably, increases up to 20% have occurred in the north west of the country and in parts of East Anglia. There have also been changes in other areas, including decreases of the same magnitude over central England. The implications of these changes are considered

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An investigation into the synthesis, structural characterisation, thermal and polymorphic behaviour of organic crystalline materials

The organic solid state appears in a complex number of forms. The design, synthesis and application of solid state organic materials have a big impact upon society, e.g. pharmaceuticals. Traditionally, the process of selecting active pharmaceutical ingredients (APIs) was limited to free drug or accepted salt formulations. The cocrystallisation of APIs with a former molecule significantly increases the developmental options for APIs. Many pharmaceutical solids are prepared as polycrystalline materials in order to deliver favourable physical properties, i.e. solubility, bioavailability and stability. In such cases, the development and application of structure solution techniques via powder X-ray diffraction (pxrd) has played an ever increasing pivotal role. In this thesis a number of new multi-component materials; oxamic acid:nicotinamide, oxamic acid:isonicotinamide, fumaric acid:nicotinamide, maleic acid:nicotinamide and maleic acid:isonicotinamide, will be synthesised, via a number of synthetic methods, and fully structurally characterised. A direct comparison of structures solved by powder and single crystal diffraction, have been made in order to evaluate the reliability of structure solution from pxrd in these types of materials. The thermal behaviour of molecular materials will be presented as significant structural information can be extracted from the anisotropic expansion of molecular materials. In conjunction with the research into new multi-component materials, the structure solution of oxamic acid via pxrd, single X-ray diffraction and neutron diffraction will be investigated. Small organic molecular materials like oxamic acid provide a challenge to the crystallographer due to the similarities in the electron density surrounding each functional group in the molecule

Mucosal immune responses following intestinal nematode infection.

In most natural environments, the large majority of mammals harbour parasitic helminths that often live as adults within the intestine for prolonged periods (1-2 years). Although these organisms have been eradicated to a large extent within westernized human populations, those living within rural areas of developing countries continue to suffer from high infection rates. Indeed, recent estimates indicate that approximately 2.5 billion people worldwide, mainly children, currently suffer from infection with intestinal helminths (also known as geohelminths and soil-transmitted helminths) . Paradoxically, the eradication of helminths is thought to contribute to the increased incidence of autoimmune diseases and allergy observed in developed countries. In this review, we will summarize our current understanding of host-helminth interactions at the mucosal surface that result in parasite expulsion or permit the establishment of chronic infections with luminal dwelling adult worms. We will also provide insight into the adaptive immune mechanisms that provide immune protection against re-infection with helminth larvae, a process that is likely to be key to the future development of successful vaccination strategies. Lastly, the contribution of helminths to immune modulation and particularly to the treatment of allergy and inflammatory bowel disease will be discussed

Why do some asthma patients respond poorly to glucocorticoid therapy?

Glucocorticosteroids are the first-line therapy for controlling airway inflammation in asthma. They bind intracellular glucocorticoid receptors to trigger increased expression of anti-inflammatory genes and suppression of pro-inflammatory gene activation in asthmatic airways. In the majority of asthma patients, inhaled glucocorticoids are clinically efficacious, improving lung function and preventing exacerbations. However, 5–10 % of the asthmatic population respond poorly to high dose inhaled and then systemic glucocorticoids. These patients form a category of severe asthma associated with poor quality of life, increased morbidity and mortality, and constitutes a major societal and health care burden. Inadequate therapeutic responses to glucocorticoid treatment is also reported in other inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease; however, asthma represents the most studied steroid-refractory disease. Several cellular and molecular events underlying glucocorticoid resistance in asthma have been identified involving abnormalities of glucocorticoid receptor signaling pathways. These events have been strongly related to immunological dysregulation, genetic, and environmental factors such as cigarette smoking or respiratory infections. A better understanding of the multiple mechanisms associated with glucocorticoid insensitivity in asthma phenotypes could improve quality of life for people with asthma but would also provide transferrable knowledge for other inflammatory diseases. In this review, we provide an update on the molecular mechanisms behind steroid-refractory asthma. Additionally, we discuss some therapeutic options for treating those asthmatic patients who respond poorly to glucocorticoid therapy

Cytokines at the Interplay Between Asthma and Atherosclerosis?

Cardiovascular disease (CVD) is an important comorbidity in a number of chronic inflammatory diseases. However, evidence in highly prevalent respiratory disease such as asthma are still limited. Epidemiological and clinical data are not univocal in supporting the hypothesis that asthma and CVD are linked and the mechanisms of this relationship remain poorly defined. In this review, we explore the relationship between asthma and cardiovascular disease, with a specific focus on cytokine contribution to vascular dysfunction and atherosclerosis. This is important in the context of recent evidence linking broad inflammatory signaling to cardiovascular events. However inflammatory regulation in asthma is different to the one typically observed in atherosclerosis. We focus on the contribution of cytokine networks encompassing IL-4, IL-6, IL-9, IL-17A, IL-33 but also IFN-γ and TNF-α to vascular dysfunction in atherosclerosis. In doing so we highlight areas of unmet need and possible therapeutic implications

Translating a walking intervention for health professional delivery within primary care: A mixed‐methods treatment fidelity assessment

Objectives: Existing fidelity studies of physical activity interventions are limited in methodological quality and rigour, particularly those delivered by health care providers in clinical settings. The present study aimed to enhance and assess the fidelity of a walking intervention delivered by health care providers within general practice in line with the NIH Behavior Change Consortium treatment fidelity framework. / Design: Two practice nurses and six health care assistants delivered a theory‐based walking intervention to 63 patients in their own practices. A cross‐sectional mixed‐methods study assessed fidelity related to treatment delivery and treatment receipt, from the perspectives of health care providers and patients. / Methods: All providers received training and demonstrated delivery competence prior to the trial. Delivery of intervention content was coded from audio‐recordings using a standardized checklist. Qualitative interviews with 12 patients were conducted to assess patient perspectives of treatment receipt and analysed using framework analysis. / Results: Overall, 78% of intervention components were delivered as per the protocol (range 36–91%), with greater fidelity for components requiring active engagement from patients (e.g., completion of worksheets). The qualitative data highlighted differences in patients’ comprehension of specific intervention components. Understanding of, and engagement with, motivational components aimed at improving self‐efficacy was poorer than for volitional planning components. / Conclusions: High levels of fidelity of delivery were demonstrated. However, patient‐, provider‐, and component‐level factors impacted on treatment delivery and receipt. We recommend that methods for the enhancement and assessment of treatment fidelity are consistently implemented to enhance the rigour of physical activity intervention research