David Shanson

Pilot studies of azithromycin, letrazuril and paromomycin in the treatment of cryptosporidiosis:

Summary: Pilot studies of the safety and efficacy of 3 drugs thought to have anticryptosporidial activity were carried out to determine whether any of them are suitable for large-scale clinical trials. Open studies of the use of azithromycin, letrazuril and paromomycin in patients with acquired immunodeficiency syndrome (AIDS) and confirmed cryptosporidial diarrhoea for at least a month. Azithromycin 500 mg daily was ineffective. Letrazuril 150-200 mg daily was associated with an improvement in symptoms in 40% of patients treated and cessation of excretion of cryptosporidial oocysts in the stool in 70%; however biopsies remained positive. Paromomycin therapy was associated with a complete resolution of diarrhoea in 60% of patients treated and some improvement in symptoms in a further 5% but it did not eliminate the infection. None of the drugs had any major toxicities. Dose escalation studies of azithromycin should be performed. Letrazuril should be further investigated for efficacy in double-blind placebo-controlled trials. Paromomycin appears to result in prolonged symptomatic remission of cryptosporidial diarrhoea, but has no effect on cryptosporidial cholangitis.

Guidelines on prophylaxis to prevent infective endocarditis

Infective endocarditis is a devastating disease with high morbidity and mortality. The link to oral bacteria has been known for many decades and has caused ongoing concern for dentists, patients and cardiologists. Since 2008, the UK has been out of step with the rest of the world where antibiotic prophylaxis is recommended for high-risk patients undergoing invasive dental procedures. Recent evidence that identified an increase in endocarditis incidence prompted a guideline review by NICE and the European Society for Cardiology – which produces guidance for the whole of Europe. Despite reviewing the same evidence they reached completely opposing conclusions. The resulting conflict of opinions and guidance is confusing and poses difficulties for dentists, cardiologists and their patients. Recent changes in the law on consent, however, may provide a patient-centred and pragmatic solution to these problems. This Opinion piece examines the evidence and opposing guidance on antibiotic prophylaxis in the context of the recent changes in the law on consent and provides a framework for how patients at risk of endocarditis might be managed in practice.

NICE and antibiotic prophylaxis to prevent endocarditis

Infective endocarditis is a devastating disease with high morbidity and mortality. The link to oral bacteria has been known for many decades and has caused on going concern for dentists, patients and cardiologists. Good oral hygiene has long been advocated to prevent endocarditis. Before 2008, antibiotic prophylaxis before invasive dental procedures was also an important strategy for preventing infective endocarditis for patients at risk of the disease in the UK, and still is in most other countries of the world. In 2008, however, NICE published new guidance recommending that antibiotic prophylaxis in the UK should cease. At the time this was a highly controversial decision. New data suggests that there has been a significant increase in the incidence of infective endocarditis since the 2008 guidelines. The 2008 guidance is being reviewed and draft new guidance is being put out for public consultation. This article discusses the issues raised by the new data and the questions that should be addressed in the review and public consultation.

Antibiotic prophylaxis for infective endocarditis: a systematic review and meta-analysis.

Objective The use of antibiotic prophylaxis (AP) for prevention of infective endocarditis (IE) is controversial. In recent years, guidelines to cardiologists and dentists have advised restriction of AP to high-risk groups (in Europe and the USA) or against its use at all (in the UK). The objective of this systematic review was to appraise the evidence for use of AP for prevention of bacteraemia or IE in patients undergoing dental procedures. Methods We conducted electronic searches in Medline, Embase, Cochrane Library and ISI Web of Science. We assessed the methodological characteristics of included studies using the Strengthening the Reporting of Observational Studies in Epidemiology criteria for observational studies and the Cochrane Risk of Bias Tool for trials. Two reviewers independently determined the eligibility of studies, assessed the methodology of included studies and extracted the data. Results We identified 178 eligible studies, of which 36 were included in the review. This included 10 time-trend studies, 5 observational studies and 21 trials. All trials identified used bacteraemia as an endpoint rather than IE. One time-trend study suggests that total AP restriction may be associated with a rising incidence of IE, while data on the consequences of relative AP restriction are conflicting. Meta-analysis of trials indicates that AP is effective in reducing the incidence of bacteraemia (risk ratio 0.53, 95% CI 0.49 to 0.57, p<0.01), but case–control studies suggest this may not translate to a statistically significant protective effect against IE in patients at low risk of disease. Conclusions The evidence base for the use of AP is limited, heterogeneous and the methodological quality of many studies is poor. Postprocedural bacteraemia is not a good surrogate endpoint for IE. Given the logistical challenges of a randomised trial, high-quality case–control studies would help to evaluate the role of dental procedures in causing IE and the efficacy of AP in its prevention.

Valvular heart disease: a call for global collaborative research initiatives

The burden of valvular heart disease (VHD) is rising rapidly as life expectancy increases. The prevalence in the USA alone is 13% in those aged over 75 years,1 while the global prevalence of rheumatic heart disease is estimated at 15.6–19.6 million.2 Despite this, the treatment of VHD still lacks an adequate research base. None of the 64 recommendations in the 2012 European Society of Cardiology (ESC) VHD guidelines3 had Level A evidence and only 14% had Level B evidence. This compares with 28% at Level A and 42% at Level B among the 270 recommendations in the 2010 ESC myocardial revascularisation guidelines.4 Therefore, there is an urgent need to stimulate the investigation. In this article, we identify deficits in our knowledge which may be amenable to research and make a call for national and international collaborative efforts to address this evidence gap. The prevalence of VHD in industrialised countries has been extrapolated from studies predominantly conducted in the USA,1 while the prevalence of rheumatic disease in sub-Saharan Africa is extrapolated from studies in North Africa. True figures need to be established nationally, while for rare causes of VHD (eg, carcinoid or antiphospholipid syndrome), this might be better done using international registries with standardised protocols. Serial echocardiography within these projects will improve our understanding of the contemporary natural history of VHD, which was previously determined in small cohorts of patients and generally with fewer comorbidities compared with the present. The genetics and developmental biology of VHD are poorly understood. Collation of genetic analyses from established bio-banks and twin studies may identify new determinants of disease or its progression. Such techniques may also provide clues towards the development of treatments for challenging conditions such as endomyocardial fibrosis. Lipid-lowering therapy has not been successful in modifying the progression …

New guidelines and the development of an international consensus on recommendations for the antibiotic prophylaxis of infective endocarditis.

During the last five years there has been a considerable change in attitude towards antibiotic prophylaxis of endocarditis in many countries so that far fewer cardiac patients are advised to receive prophylaxis in comparison with previous years. Much greater emphasis is now given to the maintenance of good oral hygiene as the main method of preventing endocarditis and prophylaxis is only recommended for patients with the highest risk cardiac conditions undergoing dental procedures. Most countries have now abandoned prophylaxis for urological and gastrointestinal procedures. The UK National Institute for Health and Clinical Excellence guidance, which does not recommend prophylaxis for any group of patients undergoing dental procedures, is regarded as too extreme by many experts in other countries. The assertion that more patients would die from fatal anaphylaxis after oral amoxicillin, the main prophylactic agent, than would die from endocarditis because prophylaxis is withheld, may not be correct since the risks of dying after oral amoxicillin have probably been overestimated. There is a lack of clinical evidence either for or against the efficacy of antibiotic prophylaxis. Unless convincing data is obtained from future research any new international consensus guidelines will continue to be based mainly on expert opinion rather than on good evidence.

NICE v world on endocarditis prophylaxis

Articles defending the National Institute for Health and Clinical Excellence’s (NICE) advocacy of no antibiotic prophylaxis tend to suggest that the contrary position is universal antibiotic prophylaxis.1 But the essential difference between American, European, and Australian guidelines and those from NICE is in advising antibiotics for high risk cardiac patients (those with …

Antibiotic prophylaxis of endocarditis: a NICE mess

NICE guidance written in 2008, and revised in 2015, no longer recommends antibiotic prophylaxis in patients at high-risk of infective endocarditis who are undergoing high-risk dental procedures. This guidance is different from every international guideline, including a 2015 European Society of Cardiology revision. The European guideline committee considered, but rejected, the NICE view. How has this important difference in advice arisen and what are its implications?

A change in the NICE guidelines on antibiotic prophylaxis for dental procedures

We would like to add an important footnote to the article on dental problems by Renton and Wilson in the August BJGP .1 You’d be forgiven for missing it, because it was announced without fanfare, but the National Institute for Health and Care Excellence (NICE) has added the word ‘routinely’2 to Recommendation 1.1.3: ‘Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures’ [authors’ emphasis]. This change occurred after a patient with a replacement aortic valve died from infective endocarditis (IE) developing after unprotected descaling, and followed approaches …

Barnett (?Barney?) Shanson.

Barnett Shanson (“Barney”) started work with junior hospital doctor posts in anaesthetics, surgery, and rheumatology. He was a founder member of the Heberden Society, the forerunner of the British Society for Rheumatology. Subsequently he worked as a general practitioner for 45 …