A randomized clinical trial of hydroxymethylglutaryl-Coenzyme A reductase inhibition for Acute Lung Injury (The HARP study)

Rationale: There is no effective pharmacological treatment for acute lung injury (ALI). Statins are a potential new therapy because they modify many of the underlying processes important in ALI.

Objectives: To test whether simvastatin improves physiological and biological outcomes in ALI.

Methods: We conducted a randomized, double-blinded, placebo-controlled trial in patients with ALI. Patients received 80 mg simvastatin or placebo until cessation of mechanical ventilation or up to 14 days. Extravascular lung water was measured using thermodilution. Measures of pulmonary and nonpulmonary organ function were assessed daily. Pulmonary and systemic inflammation was assessed by bronchoalveolar lavage fluid and plasma cytokines. Systemic inflammation was also measured by plasma C-reactive protein.

Measurements and Main Results: Sixty patients were recruited. Baseline characteristics, including demographics and severity of illness scores, were similar in both groups. At Day 7, there was no difference in extravascular lung water. By Day 14, the simvastatin-treated group had improvements in nonpulmonary organ dysfunction. Oxygenation and respiratory mechanics improved, although these parameters failed to reach statistical significance. Intensive care unit mortality was 30% in both groups. Simvastatin was well tolerated, with no increase in adverse events. Simvastatin decreased bronchoalveolar lavage IL-8 by 2.5-fold (P = 0.04). Plasma C-reactive protein decreased in both groups but failed to achieve significance in the placebo-treated group.

Conclusions: Treatment with simvastatin appears to be safe and may be associated with an improvement in organ dysfunction in ALI. These clinical effects may be mediated by a reduction in pulmonary and systemic inflammation.

The Crowned Harp: Policing Northern Ireland (reprint 2006, 2010)

The Crowned Harp provides a detailed analysis of policing in Northern Ireland. Tracing its history from 1922, Ellison and Smyth portray the Royal Ulster Constabulary (RUC) as an organisation burdened by its past as a colonial police force. They analyse its perceived close relationship with unionism and why, for many nationalists, the RUC embodied the problem of the legitimacy of Northern Ireland, arguing that decisions made on the organisation, composition and ideology of policing in the early years of the state had consequences which went beyond the everyday practice of policing.

The authors provide an extended discussion of policing after the outbreak of civil unrest in 1969, ask why policing was cast in a paramilitary mould, and look at the use of special constabularies and the way in which the police dealt with social unrest which threatened to break down sectarian divisions. Examining the reorganisations of the RUC in the 1970s and 1980s, Ellison and Smyth focus on the various structural, legal and ideological components, the professionalisation of the force and the development of a coherent, if contradictory, ideology. The analysis of the RUC during this period sheds light on the problematic nature of using the police as a counter insurgency force in a divided society. Perceptions of the police, and the opinions of rank and file members are examined and an assessment is made of the various alternative models of policing, such as community policing and local control. This book offers important lessons about the nature of policing in divided societies.