Impact of an antimicrobial stewardship intervention on appropriateness of prescribing for community-acquired pneumonia in an Australian regional hospital.

Community-acquired pneumonia (CAP) is the second commonest indication for antibiotic use in Australian hospitals and is therefore a frequent target for antimicrobial stewardship. A single-centre prospective study was conducted in a regional referral hospital comparing management of adult patients with CAP before and after an educational intervention. We demonstrated a reduction in duration of therapy and reduced inappropriate use of ceftriaxone-based regimens for non-severe CAP.

Outcomes of multisite antimicrobial stewardship programme implementation with a shared clinical decision support system.

Background: Studies evaluating antimicrobial stewardship programmes (ASPs) supported by computerized clinical decision support systems (CDSSs) have predominantly been conducted in single site metropolitan hospitals. Objectives: To examine outcomes of multisite ASP implementation supported by a centrally deployed CDSS. Methods: An interrupted time series study was conducted across five hospitals in New South Wales, Australia, from 2010 to 2014. Outcomes analysed were: effect of the intervention on targeted antimicrobial use, antimicrobial costs and healthcare-associated Clostridium difficile infection (HCA-CDI) rates. Infection-related length of stay (LOS) and standardized mortality ratios (SMRs) were also assessed. Results: Post-intervention, antimicrobials targeted for increased use rose from 223 to 293 defined daily doses (DDDs)/1000 occupied bed days (OBDs)/month (+32%, P < 0.01). Conversely, antimicrobials targeted for decreased use fell from 254 to 196 DDDs/1000 OBDs/month (-23%; P < 0.01). These effects diminished over time. Antimicrobial costs decreased initially (-AUD$64551/month; P < 0.01), then increased (+AUD$7273/month; P < 0.01). HCA-CDI rates decreased post-intervention (-0.2 cases/10 000 OBDs/month; P < 0.01). Proportional LOS reductions for key infections (respiratory from 4.8 to 4.3 days, P < 0.01; septicaemia 6.8 to 6.1 days, P < 0.01) were similar to background LOS reductions (2.1 to 1.9 days). Similarly, infection-related SMRs (observed/expected deaths) decreased (respiratory from 1.1 to 0.75; septicaemia 1.25 to 0.8; background rate 1.19 to 0.90. Conclusions: Implementation of a collaborative multisite ASP supported by a centrally deployed CDSS was associated with changes in targeted antimicrobial use, decreased antimicrobial costs, decreased HCA-CDI rates, and no observable increase in LOS or mortality. Ongoing targeted interventions are suggested to promote sustainability.

The effect of chronic tobacco smoking on arterial stiffness.

AIMS: Cardiovascular disease caused by smoking is related to the pathophysiological burden placed on the vascular endothelium. We studied the effect of chronic cigarette smoking on arterial wave reflection (study 1) and smoking cessation on pulse wave analysis (study 2). METHODS: Fifty smokers and 50 age- and sex-matched nonsmokers participated in study 1. Study 2 recruited 20 volunteers from the stop smoking clinic at the Royal Hallamshire Hospital, Sheffield, UK. Systemic augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV) were measured using the SphygmoCor system. Brachial blood pressure (BP) (Omron 705-CP-E), AIx and PWV were recorded at a single visit in study 1. Study 2 measured these variables on 'quit day' and 4 weeks later. RESULTS: In study 1, AIx was significantly higher in smokers than in nonsmokers (median 17.25 vs. 11.75%, P = 0.004). Multiple regression analysis showed a significant correlation between AIx and age, diastolic BP, smoking status (P < 0.001), blood glucose (P = 0.045) and weight (P = 0.049). In study 2, AIx significantly reduced after 4 weeks of abstinence in successful quitters (n = 10) compared with relapsed smokers (n = 4) (median 5.0 vs.- 9.5; P = 0.013). PWV did not reach significance in either study. CONCLUSIONS: Chronic tobacco smoking is associated with endothelial dysfunction and increased AIx in subjects of a wide age range free from additional cardiovascular risk factors, which is partially reversible after 4 weeks of smoking cessation.

Prostaglandin E2 activates EP2 receptors to inhibit human lung mast cell degranulation.

The prostanoid, PGE2, is known to inhibit human lung mast cell activity. The aim of the present study was to characterize the EP receptor that mediates this effect. PGE2 (pEC(50), 5.8+/-0.1) inhibited the IgE-mediated release of histamine from mast cells in a concentration-dependent manner. Alternative EP receptor agonists were studied. The EP2-selective agonist, butaprost (pEC50, 5.2+/-0.2), was an effective inhibitor of mediator release whereas the EP1/EP3 receptor agonist, sulprostone, and the EP1-selective agonist, 17-phenyl-trinor-PGE2, were ineffective. The DP agonist PGD2, the FP agonist PGF(2alpha), the IP agonist iloprost and the TP agonist U-46619 were ineffective inhibitors of IgE-mediated histamine release from mast cells. PGE2 induced a concentration-dependent increase in intracellular cAMP levels in mast cells. The effects of the EP1/EP2 receptor antagonist, AH6809, and the EP4 receptor antagonist, AH23848, on the PGE2-mediated inhibition of histamine release were determined. AH6809 (pK(B), 5.6+/-0.1) caused a modest rightward shift in the PGE2 concentration-response curve, whereas AH23848 was ineffective. Long-term (24 h) incubation of mast cells with either PGE2 or butaprost (EP2 agonist), but not sulprostone (EP1/EP3 agonist), caused a significant reduction in the subsequent ability of PGE2 to inhibit histamine release. Collectively, these data suggest that PGE2 mediates effects on human lung mast cells by interacting with EP2 receptors.

Should we treat high-normal blood pressure?

OBJECTIVES: To examine the risk of cardiovascular disease associated with high-normal blood pressure in English adults and estimate the proportion of these individuals who are at high cardiovascular risk. DESIGN AND SETTING: Cross-sectional survey of England in 1998. PARTICIPANTS: Nationally representative sample of 12,341 individuals aged 18-80 years living in private households in England. MAIN OUTCOME MEASURE: Percentage of individuals with high-normal blood pressure who have cardiovascular disease, diabetes mellitus or a 10-year cardiovascular event risk of at least 20%. RESULTS: Of the 12,341 participants, 2413 (19.6%) had high-normal blood pressure. About 5.3% of those aged 18-80 years with high-normal blood pressure had cardiovascular disease or diabetes, and a further 7.6% were at a predicted cardiovascular event risk of at least 20% over 10 years. The mean predicted risk was 8.7% for men and 6.3% for women in the high-normal blood pressure category. The majority of men aged 61-80 years were at high cardiovascular risk. On average, men and women with high-normal blood pressure had a greater incidence of cardiovascular disease and diabetes mellitus, and a greater predicted mean cardiovascular risk than those with normal blood pressure. Extending antihypertensive treatment to individuals with high-normal blood pressure who are at high cardiovascular risk would involve treating an additional 2.5% of the English population aged 18-80 years. CONCLUSION: These findings support the view that individuals with high-normal blood pressure at high risk for cardiovascular disease should be targeted for blood pressure-lowering treatment.

Coronary risk versus cardiovascular risk for treatment decisions in mild hypertension.

BACKGROUND: British guidelines recommend treatment for mild hypertension at a cardiovascular (CVD) risk threshold of 20% over 10 years. However, treatment is targeted at the equivalent coronary (CHD) risk of 15% over 10 years. We examined the relationship between CHD and CVD risk in men and women with mild hypertension and assessed the accuracy of using a 10-year CHD risk threshold of 15% to identify patients at a 10-year CVD risk > or = 20%. DESIGN: Cross-sectional survey of England in 1998. METHODS: We identified 5588 subjects aged 35-74 years free of cardiovascular disease with complete data for risk assessment. Of these, 1364 (24.4%) had mild hypertension (systolic pressure 140-159 mmHg or diastolic pressure 90-99 mmHg). The Framingham functions were used to estimate CHD and CVD event risk for each individual. RESULTS: At a 10-year CHD risk of 15%, the corresponding 10-year CVD risk for men and women, respectively was 20% and 21% in those aged < 55 years, and 24% and 25% in those aged > or = 55 years. Using a 10-year CHD risk threshold of 15% to identify patients at a 10-year CVD risk > or = 20% had high specificity (>96%) in all four groups. For men and women respectively, the sensitivity was 73% (62-84%) and 62% (35-88%) in younger subjects, and 89% (85-93%) and 47% (38-56%) in older subjects. CONCLUSION: Using a 10-year CHD risk of 15% to target patients at a 10-year CVD risk > or = 20% was reasonably accurate for men but missed about 50% of women eligible for antihypertensive treatment.