Priming the brain to learn: The future of therapy?

Neuromodulatory techniques with the ability to alter cortical excitability are gaining interest for their potential to enhance the brain's sensitivity to traditional therapies. Neuromodulatory techniques that prime the brain prior to manual or exercise therapy hold therapeutic promise for enhancing clinical outcomes in musculoskeletal and neurological conditions. The integration of these techniques into physiotherapy practice represents an exciting opportunity for the therapists of the future. Here, an overview is provided of three neuromodulatory techniques (peripheral electrical stimulation, transcranial direct current stimulation and repetitive transcranial magnetic stimulation) and the potential implications of these techniques for therapists discussed. Understanding these techniques and their therapeutic implications will ensure that therapists are well positioned to contribute to their clinical translation and adoption into clinical practice in an appropriate time frame. A therapeutic landscape defined by neuromodulatory techniques and improved clinical outcomes across a range of conditions is no longer far-fetched.     

Personalized antiplatelet therapy for coronary artery disease patients: is this the future?

Clopidogrel has decreased the rate of thrombotic events in patients undergoing percutaneous coronary intervention. However, two major limitations of the drug have been involved in the persistence of a relatively high rate of adverse events. The recent literature suggested that improved platelet reactivity inhibition using a higher or tailored dose of clopidogrel, or a more potent agent, could reduce the rate of events. The development of new antiplatelet agents and the increasing availability of platelet assays are likely to profoundly modify current practice and favor personalized antiplatelet therapy.     

Genetic testing: the future of smoking cessation therapy?

In the UK, approximately one-third of the population currently smoke. It is estimated that up to 70% of these smokers want to stop smoking but smoking cessation rates currently only stand at 20-30%. In order to reduce the health burden associated with smoking in the short-term we need to increase cessation rates. This will stem from deeper understanding of the processes involved in nicotine addiction, targeted therapy and the development of new pharmacological cessation agents. This article is not intended to be an exhaustive examination of nicotine addiction but rather an overview of some of the genetic aspects and how we can go on to use this knowledge in order to develop a genetic test to aid smoking cessation.     

Alemtuzumab: what is the secret to safe therapy?

Over the past decade, the use of the monoclonal antibody alemtuzumab in chronic lymphocytic leukemia has expanded from administration as a single-agent therapy, into use in combination with fludarabine or rituximab, and further to use as a consolidation agent with the goal of eradicating minimal residual disease. Numerous clinical studies have shown that alemtuzumab is effective as first-line treatment and in patients who have relapsed disease or who are refractory to fludarabine. Despite improvements in response rates and survival compared with combination chemotherapy, there remains some hesitation to incorporate alemtuzumab into management because of known toxicities. Adverse events in patients treated with standard-dose, single-agent alemtuzumab occur at generally predictable time points during treatment and can be managed effectively; this outcome is less established when alemtuzumab is incorporated into combination regimens. Variability in alemtuzumab dosing, route of administration, and duration of therapy has led to inconsistent and sometimes adverse safety consequences. This article presents an overview of clinical studies with alemtuzumab as a single agent, in combination, or in consolidation, with discussion of toxicity and suggestions for ensuring that the efficacious outcomes following alemtuzumab therapy are not outweighed by safety concerns.     

Microcurrent therapy; wave of the future?

In our six years of experience with muscular electrical nerve stimulation (MENS), we have not had any negative results. MENS has produced consistent, predictable results on a variety of patients. The results were initially excellent and have improved with our familiarization with the instrumentation. We would encourage clinicians who have not utilized MENS to do so. Optimal results with MENS will require a combination of direct, indirect, and regional techniques.     

Plasma for burn shock resuscitation: is it time to go back to the future?

Patients with burn shock can be challenging to resuscitate. Burn shock produces a variety of physiologic derangements: Patients are hypovolemic from volume loss, have a increased systemic vascular resistance, and may have a depressed cardiac output depending on the extent of the thermal injury. Additionally, the burn wound produces a significant inflammatory cascade of events that contributes to the shock state. Fluid resuscitation is foundational for the initial treatment of burn shock. Typical resuscitation is with intravenous lactated Ringer's in accordance with well‐established formulas based on burn wound size. In the past century, as therapies to treat thermal injuries were being developed, plasma was the fluid used for burn resuscitation; in fact, plasma was used in World War II and throughout the 1950s and 1960s. Plasma was abandoned because of infectious risks and complications. Despite huge strides in transfusion medicine and the increased safety of blood products, plasma has never been readopted for burn resuscitation. Over the past 15 years, there has been a paradigm shift in trauma resuscitation: Less crystalloid and more blood products are used; this strategy has demonstrated improved outcomes. Plasma is a physiologic fluid that stabilizes the endothelium. The endotheliopathy of trauma has been described and is mitigated by transfusion strategies with a 1:1 ratio of RBCs to plasma. Thermal injury also results in endothelial dysfunction: the endotheliopathy of burns. Plasma is likely a better resuscitation fluid for patients with significant burn wounds because of its capability to restore intravascular volume status and treat the endotheliopathy of burns.     

What is the appropriate outcome for studies of treatments for out-of-hospital cardiac arrest?

BACKGROUND: A good outcome following out-of-hospital medical care for cardiac arrest is survival to hospital discharge. Because a large number of patients are required to detect a minimum clinically important difference in survival, an intermediate outcome such as hospital admittance is commonly used. For an intermediate outcome to be a useful surrogate, the survival rate conditional on achieving the intermediate outcome should not depend upon the field treatment. If so, an advantage of the intermediate outcome may be a smaller sample size. However, recent trials demonstrate that survival conditional on admittance may depend upon the field treatment. Even if the resources are available to power a study for survival, is survival the right outcome? For example, no increase in survival and a large increase in admittance could be considered a bad result, as it represents a substantial waste of resources. Similarly no increase in mortality and a decrease in admittance should be considered a good result, as it represents a substantial cost savings without any sacrifice of life. Both admittance and survival are important outcomes and need to be considered jointly, that is, as a bivariate outcome. METHODS: Cost-effectiveness concepts are used to distinguish between a good and bad (bivariate) outcome. Simulations are conducted to compare the impact of the univariate and the bivariate outcomes in a variety of trial scenarios. A table of sample sizes is computed for the bivariate outcome across a range of trial scenarios. RESULTS: The bivariate outcome outperforms both univariate outcomes for most alternatives. The required sample size for the joint outcome of admittance and survival may be substantially, over 50%, less than that for the survival outcome alone. CONCLUSION: Use of the bivariate outcome could provide more informed decision making about resuscitation strategies and at less cost then the current gold standard of hospital survival.     

Are Th17 cells an appropriate new target in the treatment of rheumatoid arthritis?

Th17 cells play crucial roles not only in host defense but also in many human autoimmune diseases and corresponding animal models. Although many of the fundamental principles regarding Th17 biology have been rapidly elucidated in mice, there remain numerous controversies regarding the differentiation, plasticity, and pathogenicity of human Th17 cells. In this review, we consider these open questions in comparison to what has already been clarified in mice, and discuss the potential impact of discoveries related to the Th17 pathway on the development of new therapeutic strategies in Th17 driven autoimmune diseases, specifically rheumatoid arthritis.