Background Antibiotic prophylaxis (AP) administered prior to invasive procedures in patients at risk of developing infective endocarditis (IE) has historically been the focus of IE prevention. Recent changes in AP guidelines in the US and Europe have substantially reduced the numbers for whom AP is recommended. In the UK, the National Institute for Health and Care Excellence (NICE) guidelines recommended complete cessation of AP in March 2008. We report the impact of these guidelines on AP prescribing; in addition, IE incidence was examined following the introduction of the guidelines. Methods We analyzed English AP prescribing data from January 2004 to March 2013 and hospital discharge episode statistics for patients with a primary diagnosis of IE from January 2000 to March 2013. Findings AP prescribing rates fell dramatically after introduction of the NICE guidance (10,935 prescriptions/month vs. 2,236 prescriptions/month, p<0·0001). Commencing in March 2008, there was also a significant increase in the number of IE cases/month (0·11 cases/10million/month, CI 0·05–0·16, p<0·0001) above the projected historical trend. By March 2013, there were an additional 35 cases/month than would have been expected if the previous trend had continued. This increase in IE incidence was significant for both ‘high-risk’ and ‘lower-risk’ individuals. Interpretation Although our data do not establish a causal relationship, there has been a substantial reduction in AP prescribing and a significant increase in IE incidence in England since introduction of the NICE guidelines in 2008. Funding Different aspects of this study were supported by Heart Research UK and Simplyhealth [Grant Ref: RG2632/13/14] and NIDCR R03 grant [Ref: 1R03DE023092-01] from the National Institutes for Health.

Decline in fat free mass in COPD is associated with worse lung function, continued cigarette consumption and frequent exacerbations. Factors predicting progression of quadriceps weakness could not be identified from the present cohort.

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AP adverse drug reaction reporting rates in England were low, particularly for amoxicillin, and lower than previous estimates. This suggests that amoxicillin AP is comparatively safe for patients without a history of amoxicillin allergy. The use of clindamycin AP was, however, associated with significant rates of fatal and non-fatal adverse drug reactions associated with C. difficile infections. These were higher than expected and similar to those for other doses, durations and routes of clindamycin administration.

Background: Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown. Aim: The aim of this study was to determine the prevalence and characteristics of SDB in male patients with NYHA class II symptoms of CHF. Methods and results: 55 male patients with mild symptomatic CHF underwent assessment of quality of life, echocardiography, cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive sleep apnoea. SDB patients had steeper VE/VCO 2 slope [median (inter-quartile range) 31.1 (28-37) vs. 28.1 (27-30) respectively; p = 0.04], enhanced chemoreflexes to carbon dioxide during wakefulness [mean ± sd: 2.4 ± 1.6 vs. 1.5 ± 0.7 %VE Max/ mmHg CO 2 respectively; p = 0.03], and significantly higher levels of brain natriuretic peptide and endothelin-1 compared to patients without SDB. No differences in left ventricular ejection fraction, percent predicted peak oxygen uptake, or symptoms of SDB were observed. Conclusions: A high prevalence of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be differentiated by symptoms or by routine cardiac assessment making clinical diagnosis of SDB in CHF difficult.

National Institute for Health Research.

In this third update of the Cochrane review, there were no differences in effects of homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo on myocardial infarction, death from any cause or adverse events. In terms of stroke, this review found a small difference in effect favouring to homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo.There were uncertain effects of enalapril plus folic acid compared with enalapril on stroke; approximately 143 (95% CI 85 to 428) people would need to be treated for 5.4 years to prevent 1 stroke, this evidence emerged from one mega-trial.Trial sequential analyses showed that additional trials are unlikely to increase the certainty about the findings of this issue regarding homocysteine-lowering interventions versus placebo. There is a need for additional trials comparing homocysteine-lowering interventions combined with antihypertensive medication versus antihypertensive medication, and homocysteine-lowering interventions at high doses versus homocysteine-lowering interventions at low doses. Potential trials should be large and co-operative.

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