The Beta Agonist Lung Injury Trial Prevention:A Randomized Controlled Trial

Rationale: Experimental studies suggest that pretreatment with b-agonists might prevent acute lung injury (ALI).

Objectives: To determine if in adult patients undergoing elective esophagectomy, perioperative treatment with inhaled b-agonists effects the development of early ALI.

Methods:We conducted a randomized placebo-controlled trial in 12 UK centers (2008-2011). Adult patients undergoing elective esophagectomy were allocated to prerandomized, sequentially numbered treatment packs containing inhaled salmeterol (100 mg twice daily) or a matching placebo. Patients, clinicians, and researchers were masked to treatment allocation. The primary outcome was development of ALI within 72 hours of surgery. Secondary outcomes were ALI within 28 days, organ failure, adverse events, survival, and health-related quality of life. An exploratory substudy measured biomarkers of alveolar-capillary inflammation and injury.

Measurements and Main Results: A total of 179 patients were randomized to salmeterol and 183 to placebo. Baseline characteristics were similar. Treatment with salmeterol did not prevent early lung injury (32 [19.2%] of 168 vs. 27 [16.0%] of 170; odds ratio [OR], 1.25; 95% confidence interval [CI], 0.71-2.22). There was no difference in organ failure, survival, or health-related quality of life.Adverse events were less frequent in the salmeterol group (55 vs. 70; OR, 0.63; 95% CI, 0.39-0.99), predominantly because of a lower number of pneumonia (7 vs. 17; OR, 0.39; 95% CI, 0.16-0.96). Salmeterol reduced some biomarkers of alveolar inflammation and epithelial injury.

Conclusion: Perioperative treatment with inhaled salmeterol was well tolerated but did not prevent ALI.

Clinical trial registered with International Standard Randomized Controlled Trial Register (ISRCTN47481946) and European Union database of randomized Controlled Trials (EudraCT 2007-004096-19).Copyright © 2014 by the American Thoracic Society.

Beyond HIV microbicides: multipurpose prevention technology (MPT) products

Multi-purpose prevention technologies (MPTs) that aim to simultaneously prevent unintended pregnancy, human immunodeficiency virus type 1 (HIV-1) infection and other sexually transmitted infections (STIs) are among the most innovative and complex products currently in development within women’s sexual and reproductive healthcare. In this review article, MPTs are placed within the wider context of combination products, combination drug products and multi-indication products. The current MPT product landscape is mapped and assessed with reference to existing products for the corresponding single indications, before identifying the gaps in the current MPT product pipeline and highlighting priority products and challenges moving forward.

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial

Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.

Banking compliance and dependence corruption: towards an attachment perspective

Why did banking compliance fail so badly in the recent financial crisis and why, according to many, does it continue to do so? Rather than point to the lack of oversight of individuals in bank compliance roles, as many commentators do, in this paper I examine in depth the organizational context that surrounded people in such roles. I focus on those compliance personnel who did speak out about risky practices in their banks, who were forced to escalate the problem and 'whistle-blow' to external parties, and who were punished for doing so. Drawing on recent empirical data from a wider study, I argue that the concept of dependence corruption is useful in this setting, and that it can be extended to encompass interpersonal attachments. This, in turn, problematises the concept of dependence corruption because interpersonal attachments in organisational settings are inevitable. The paper engages with recent debates on whether institutional corruption is an appropriate lens for studying private-sector organisations by arguing for a focus on roles, rather than remaining at the level of institutional fields or individual organisations. Finally, the paper contributes to studies on banking compliance in the context of the recent crisis; without a deeper understanding of those who were forced to extremes to simply do their jobs, reform of the banking sector will prove difficult.

Pre-intravitrael injection preparation: endophthalmitis prevention and the importance of povidone-iodine

Despite adherence to strict standards of care in preparation for intravitreal injections, endophthalmitis can still occur. This article focuses on endophthalmitis and the importance of povidone-iodine in pre-procedure antisepsis. An overview of endophthalmitis and an examination of the benefits of povidone-iodine in ocular aseptic technique for the prevention of post-procedure endophthalmitis are provided. The misconceptions that patients and health practitioners may have in relation to povidone-iodine hypersensitivity are also explored.

An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): Protocol for a randomized controlled trial

Background

Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients.

This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μg.kg^-1.min^-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom.

This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action.

Getting Away With It:Corruption, Moral Indignation and the Limits of Legal Accountability

In this paper we address the idea of ‘legal but corrupt’ through a discussion of two cases: abuse scandals in the Irish Catholic Church and the financial services industry in the wake of the Global Financial Crisis. We identify two important dynamics that generated the scandals: that they were driven by strong and stable groups existing within a peculiar kind of ‘accountability space’ that we describe as ‘monastic’ and that those groups persisted with tacit or explicit support from the state. ‘Legal but corrupt’ is, we argue, a matter of insider incomprehension sustained by the ceding of sovereignty over some aspect of social or economic life.