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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