The electrocardiogram for sepsis: how close are we?

In daily clinical practice the diagnosis of sepsis is imprecise and often delayed. In part, this is because the diagnosis is based on a clinical picture of signs and symptoms. This basis has significant implications, as there is evidence that early events in sepsis may determine outcome. A more objective set of measurements for confirming the diagnosis of sepsis has long been sought. Several sepsis biomarkers have been evaluated and shown to have a moderate degree of sensitivity and specificity for diagnosing the presence of bacterial infection. Efforts are now being directed toward evaluating the utility of biomarker profiles, containing multiple markers, for risk assessment and diagnosis in patients with suspected sepsis

Management of severe sepsis : advances, challenges, and current status

The complexity of treating severe sepsis and septic shock has been elucidated in myriad studies, particularly in the past 10 years. The development of clinical guidelines, insight into the effect of bundle elements, and results of clinical trials have brought to light further opportunities and questions in the approach to pharmaceutical interventions for the global challenge to save lives and reduce healthcare costs. Therapeutic interventions including fluid resuscitation, hemodynamic monitoring, glycemic control, corticosteroids, and antimicrobial therapy and stewardship inform outcomes. Research on biomarkers, use of mesenchymal stem cells, blood purification, immunoglobulins, and antioxidative treatments apropos the immune response may soon yield viable therapies

The SOFA score-development, utility and challenges of accurate assessment in clinical trials.

The Sequential Organ Failure Assessment or SOFA score was developed to assess the acute morbidity of critical illness at a population level and has been widely validated as a tool for this purpose across a range of healthcare settings and environments.In recent years, the SOFA score has become extensively used in a range of other applications. A change in the SOFA score of 2 or more is now a defining characteristic of the sepsis syndrome, and the European Medicines Agency has accepted that a change in the SOFA score is an acceptable surrogate marker of efficacy in exploratory trials of novel therapeutic agents in sepsis. The requirement to detect modest serial changes in a patients' SOFA score therefore means that increased clarity on how the score should be assessed in different circumstances is required.This review explores the development of the SOFA score, its applications and the challenges associated with measurement. In addition, it proposes guidance designed to facilitate the consistent and valid assessment of the score in multicentre sepsis trials involving novel therapeutic agents or interventions.ConclusionThe SOFA score is an increasingly important tool in defining both the clinical condition of the individual patient and the response to therapies in the context of clinical trials. Standardisation between different assessors in widespread centres is key to detecting response to treatment if the SOFA score is to be used as an outcome in sepsis clinical trials

Drugs and Criminal Responsibility

This Special Project has carried out three broad purposes.First, it has synthesized and organized materials concerning drugs and criminal responsibility into a useful guide for legal practitioners and others interested in the problems of the drug dependent defendant. Second, it has identified serious analytical flaws in many of the defenses available to the criminal defendant. Finally,it has responded to these deficiencies with proposals intended to protect not only the legal rights of the drug dependent defendant but also the rights of society pertaining to criminal justice. While these societal interests include the swift imposition of criminal penalties when warranted, they should not be allowed to diminish the concomitant rights of the criminal defendant. In fact, societal rights would be better served by a reexamination and reinterpretation of several traditional legal theories concerning drugs and criminal defendants. A recognition by courts and legislatures of the existing analytical flaws should lead to the development of more equitable theories and a search for alternative forms of treatment and rehabilitation for the drug dependent defendant. Rather than hiding behind the guise of legal history and moral judgment, courts and legislatures should respond to illogical and insufficient theories that fail to deal with the drug dependent defendant in an equitable and just manner