Wednesday, September 13, 2017

More Than a Buzz…


Adonica I. Kauwe
PhD Student
College of Nursing
University of Utah


In recent literature, terms such as transdisciplinarity and translational research have become popular – “buzz words”. Because healthcare is rapidly changing, the increasing demands for specialization of healthcare professionals and challenges for collaboration between specialists causes an emerging dilemma (Hall & Weaver, 2001). Perhaps these terms are more than just “buzz words” and may, in fact, provide critical strategies for new nursing theories and models addressing complex and often chronic conditions, such as noncommunicable diseases and associated complications.

Because nursing is a human science with holistic assessments and interventions, the nurse’s role is in itself complex and dynamic. Role confusion for nurses may be an unintended outcome of utilizing transdisciplinary and translational research models. However, because of the holistic and comprehensive knowledge and skills of nurses, the possibilities associated with utilizing such models are limitless. The following is meant to serve as one example of utilizing transdisciplinary and translational methods:
  • Health Issue – chronic wounds
  • Various disciplines working together – transdisciplinary teamwork/transdisciplinarity
  • Transforming scientific findings into application – translational nursing

Lens: Wounds and Chronic Wounds
Wounds and infections are an underappreciated but serious complication for a diverse spectrum of diseases, especially for high-risk groups, such as persons with diabetes (Kalan et al., 2016). In the U.S. in 2000, approximately 40 million inpatient surgical procedures and 31.5 million outpatient surgeries were performed.  Increasing health care costs, an aging population, and sharp rise in the incidence of diabetes and obesity worldwide is a major and snowballing threat to public health and the economy (Sen, et al., 2009). Chronic wounds are unable to heal due to cellular and molecular abnormalities within the wound bed, prohibiting the timely and orderly repairing process (Broderick, 2009).

Lens: Economic Impact
             In the U.S. alone, it is estimated that chronic wounds affect approximately 6.5 million patients and more than $25 billion is spent annually on treatments (Sen, et al., 2009). Because of multiple variables, monetary global economic impact is difficult to quantify. However, of the 57 million global deaths in 2008, 36 million were due to noncommunicable diseases (NCDs) and nearly 80 percent of these deaths – 29 million – occurred in low- and middle-income countries (WHO, 2008). The challenges of NCDs (cardiovascular disease, cancer, diabetes, etc.) and associated complications such as wounds are particularly acute in the Pacific Islands, which have some of the highest rates of diabetes and obesity in the world. In 2011, at the 42nd Pacific Islands Forum Communique, Pacific leaders expressed their deep concern “that an estimated 75 percent of all adult deaths in the Pacific were due to NCDs, with the majority of the deaths occurring in adults in the economically active age bracket.” Pacific leaders also declared NCDs have become a “human, social, and economic crisis” (Anderson, 2014).

Lens: Government
             The World Health Organization’s Non-communicable Diseases Country Profile for Samoa (2011) indicates that 70 percent of the total mortality rate is directly associated with non-communicable diseases (NCDs). According to Dr. Tuitama Leao Talalelei Tuitama, the Samoan Minister of Health, the number one cause of mortality in Samoa is directly related to NCDs, specifically chronic wounds, infection, and sepsis, usually subsequent to type 2 diabetes. As antimicrobial resistance increases, infections and chronic wounds are steadily becoming of paramount concern, especially for Samoa because of limited access to preventative and effective treatments. Furthermore, chronic wounds, infection, and sepsis involve longer lengths of stays in clinics and hospitals for patients as well as advanced treatments amplifying the associated burdens in an already resource-limited country.

Lens: Bio-organic Chemistry and Microbiology
          Recent scientific studies have identified the presence of surface-associated bacterial communities called biofilms (complex microbial communities) in chronic wounds (Bozkurt-Guzel, Savage, and Gerceker, 2011).  Bacteria living in these biofilm communities are protected from natural immunity and are up to 5,000 times more resistant to antibiotics than planktonic (free-floating) bacteria (Ding et al., 2004). Expanded microbiome research in chronic wounds indicates fungal communities (the mycobiome) form mixed fungal-bacterial biofilms further delaying wound healing, causing further complications such as amputations, and impeding clinical outcomes (Kalan et al., 2016; Hurlow, 2015).

Ceragenins were developed as mimics of endogenous antimicrobial peptides (AMPs). To fully understand the potential applications of ceragenins requires an understanding of the roles that endogenous AMPs play in higher organisms. AMPs play a key role in innate immunity, have antimicrobial activity, sequester fungal-bacterial biofilms, and inhibit local inflammatory responses. Additionally, AMPs trigger processes essential for wound healing, and multiple AMPs have been characterized as accelerators of wound healing. However, AMPs are subject to proteolytic degradation and are cost prohibitive to manufacture in large scales (Savage, 2015-17).  
Chemical structure of CSA-8. Retrieved from https://commons.wikimedia.org/wiki/File:CSA-8.png

Ceragenins effectively mimic the antibacterial, anti-inflammatory and wound healing properties of AMPs (Lai et al., 2009; Mangoni, Mcdermott, & Zasloff, 2016; Bucki, Sostarecz, Byfield, Savage, & Janmey, 2007).  Ceragenins are broad-spectrum antimicrobial agents; they are highly active against Gram-positive and -negative bacteria, generally at concentrations far below those required for comparable activity with AMPs (Lai et al., 2009; Durnaś et al., 2016; Vila-Farréset al., 2015; Wnorowska et al., 2015; Leszczynska et al., 2014; Bozkurt-Guzel, Savage, & Gerceker, 2011). Ceragenins are actively bactericidal and kill bacteria within established biofilms (Nagant et al., 2013; Pollard et al., 2009). Ceragenins retain activity against drug-resistant bacteria, including colistin-resistant Gram-negative organisms Vila-Farréset al., 2015; Saha, Savage, & Bal, 2008; Chin, Jones, Sader, Savage, & Rybak, 2007; Chin, Rybak, Cheung, & Savage, 2007). Ceragenins are potent antifungal agents and display activity against lipid-enveloped viruses (Durnaś et al., 2016; Howell et al., 2009). Ceragenins sequester bacterial endotoxins, inhibiting release of inflammatory cytokines (Bucki et al., 2007). Ceragenins promote wound healing by mimicking the effects of human AMP LL-37 triggering neovascularization and bone regrowth (Schindeler et al., 2015). Because ceragenins effectively reproduce the antibacterial, anti-fungal, antiviral, anti-inflammatory, and wound healing properties of AMPs, without the constraints of proteolytic degradation, engenderment of resistance, or high manufacturing costs, they provide an attractive alternative for use of AMPs in wound care, infection, etc. 

Lens: Nursing

Optimal management of chronic wounds and wound infections is essential not only to promote a good healing response, but also because of the significant morbidity and mortality associated with wound infections (Edwards & Harding, 2004 Often the first-point of patient contact, nurses play a vital role in efforts to support wound healing. The presence of biofilms is now well accepted in wound science as an important risk factor for wound chronicity, including infections and prolonged inflammation. Though barriers exist, such as deficient understanding of exactly how biofilms impair healing, lack of technologies needed for clinical diagnosing of biofilms, and cost-effective treatments, the nursing profession, collectively, offers unique and dynamic perspectives (Hurlow, 2016). 

Transdisciplinarity and Translational Science

            Transdisciplinarity has been defined as “holistic schemes that subordinate disciplines, looking at the dynamics of whole systems” and is more than drawing on independent disciplines. Rather transdisciplinarity requires a common perspective that “transcends” those standards in independent disciplines (Choi & Pak, 2006). Because wounds, chronic wounds and infections are often associated with co-morbid conditions such as obesity and diabetes, the complexities to effectively address these challenges in the clinical setting are multifaceted. Wounds and infections continue to be a major and snowballing threat to public health and economies (WHO, 2011 & NIH, 2010).

Effective treatments and defining characteristics for biofilm infections within chronic wounds have yet to be resolved. A comprehensive approach that is effective, efficient, equitable, affordable, and sustainable in addressing NCDs and subsequent chronic wounds, infection, and sepsis is critical. Transdisciplinarity and translational science are more than a buzz; they are inevitable strategies necessary in creating effective methods and models for improving wound healing and overall health!   

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