CME Accredited Presentation to Edmonton West Primary Care Network - May 2015
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Bugs, Drugs & “Silver Bullets” Lindsay Kalan, PhD PCN West May 28, 2015
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Presentation made to family physicians about antibiotic resistance, the cost of wounds to the health system, biofilms and silver technology.
Transcript of CME Accredited Presentation to Edmonton West Primary Care Network - May 2015
PowerPoint Presentation
Bugs, Drugs & Silver Bullets
Lindsay Kalan, PhD
PCN West
May 28, 2015
This is a picture of a multi-drug resistant psuedomonasa isolated from a wound and growing as a biofilm.
1
Faculty/Presenter Disclosure
Faculty: Dr. Lindsay Kalan
Relationships with commercial interests:
Other: Employee of Exciton Technologies Inc. (Manufacturer of Exsalt Wound Dressings)
This program has received in-kind support from Exciton Technologies in the form of clinical information tools and literature.
Potential for conflict(s) of interest:
Dr. Lindsay Kalan has received salary from Exciton whose product(s) will being discussed in this program.
Exciton Technologies Inc develops and benefits from the sale of a product that will be discussed in this program: Exsalt SD7 and T7 Wound Dressings with Ag Oxysalts.
There is a potential for bias in slides 40-44. This has been mitigated by providing full references, referring to scientific names and providing materials/methods and raw data for experimental results.
This slide must be visually presented to the audience AND verbalized by the speaker.
2
Disclosure of Commercial Support
This program has received in-kind support from Exciton Technologies in the form of clinical information tools and literature.
Potential for conflict(s) of interest:
Dr. Lindsay Kalan has received salary from Exciton whose product(s) will being discussed in this program.
Exciton Technologies Inc develops and benefits from the sale of a product that will be discussed in this program: Exsalt SD7 and T7 Wound Dressings with Ag Oxysalts.
This slide must be visually presented to the audience AND verbalized by the speaker.
3
Mitigating Potential Bias
There is a potential for bias in slides 40-44. This has been mitigated by providing full references, referring to scientific names and providing materials/methods and raw data for experimental results.
This slide must be visually presented to the audience AND verbalized by the speaker.
4
Learning Objectives
Antibiotic Resistance and Wound Infection
Biofilms 101
Biofilms in chronic wounds
The use of silver as a topical antimicrobial
Applying antibiotic stewardship and new research knowledge to clinical methodology and practice
5
For the education, list world leaders in silver dressings and the type of silver they utilize.
5
6
The Cost of a Wound
$ 3.9 Billion CND/year more than care for stroke
30-50% of all health care involves wounds
In the US >$25 Billion USD/year1
30% of DPN cost go towards wounds ($10B/yr)
Additional $35-45B/yr spent on SSI2
Dont include indirect and intangible costs associated with quality of life and society as a whole
1Sen et al. 2009. Human Skin Wounds: A Major Snowballing Threat to Public Health and the Economy
2Scott, R.D. 2009. The Direct Medical Cost of Hospital Acquired Infection in US Hospitals and the Benefits of Prevention
87% of DFU are infected.
6
Antibiotic Resistance
In 2013 - 23 million antibiotic Rx were written in Canada
45% respiratory, 16% upper respiratory, 14% UTI, 10% ear, 20% other
Many of these infections may not have required antibiotic therapy (eg. virus)
The CDC estimates >$20B in excess health care costs
>$35B in other societal costs and >8 million additional hospital days
7
No ESKAPE
http//www.sciencephoto.commedia11428enlarge
http://phil.cdc.gov/phil/home.asp
Staphylococcus aureus
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas aeruginosa
Enterobacter spp.
Enterococcus faecium
Plus: Totally drug resistant TB, C. difficile, N. gonorrhoeae and more
VRE
MRSA/VRSA
CRE
CRE
MDRPA
MDRAB
The Infectious Disease Society of America has recognized these pathogens as the most dangerous in the treatment of ongoing bacterial infections.
ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species; clockwise from top centre) are considered the greatest threat in the hospital setting due to their significant presence (responsible for more than 40% of infections in intensive care units) and their exceptional ability to evade the lethal effects of antibiotics.
Generally these pathogens infect opportunistically via open wounds, catheters, breathing tubes. As such they are the causes of respiratory tract infections and urinary tract infections
8
Why is this happening?
9
Q. Where do antibiotics come from?
A. Bacteria
http://microbewiki.kenyon.edu/index.php/Streptomyces
Environmental microbes make antibiotics and have self resistance which can be transferred to pathogens
Alexander Flemings Nobel Laureate Speech
He defined the term antibiotic as a chemical agent produced by one microorganism to destroy another microorganism
10
The Antibiotic Resistome
Introduce concept of resistome. Antibiotic resistance genes are ubiquitous. They are found in the organisms that produce the antibiotic as protection mechanisms, they are found in clinical pathogens, they are found in the environment in organisms that neither produce the antibiotic or cause infection. Finally, we see this idea of precursor genes that could be future indicators of resistance, as there is reason to believe resistance genes have evolved from genes involved in basic cellular processes.
11
Clinical Pathogens
Precursor Genes
Resistance Genes
Producers
Environmental Organisms
Antibiotic Resistance is Natural
Bacteria in these caves have been isolated for an estimated 4 million years
They are on average resistant to 3-4 clinically used antibiotics
Sealed from the surface for 4 million years. Some resistant to 14 different antibiotics.
12
Glycopeptide Antibiotics
Front-line treatment for serious Gram-positive infection (MRSA)
Two used clinically vancomycin and teicoplanin
Three second-generation televancin (2009), oritovancin, dalbavancin (2014)
All have the same primary mechanism of action
Resistance exists for all
Use glycopeptides as an example of this.
13
How Old is it?
Probe DNA extracted from permafrost cores for resistance genes
6 permafrost soil cores from eastern Beringia (Yukon)
25.3ky (stadial)
80-90ky (interstadial)
740ky (interglacial)
DCosta et al. 2011. Nature
Resistance mechanism consistent with contemporary (VRE) clinical pathogens discovered
Explain that we probed DNA, found a full length ORF for vanA. Had is synthesized and looked at structure and enzyme activity compared to contemporary vanAs
Spiked outside with GFP expressing E. coli to ensure no outside contamination. Able to get a full length open reading frame of the vanA which resulted in 4 unique sequences with high identity to modern VanAs (
14
Resistance is Widespread and Diverse
VRE vanA
VRE vanB
S. coelicolor
A. balhimycina
S. toyocaensis
P. apiarius PA-B2B
S
R
H
A
X
Y
Z
S
R
H
B
X
W
Y
K
S
R
H
ASc
X
J
K
H
ASt
X
S
R
murF
S
R
H
APa
X
Y
Z
W
S
R
H
ABh
X
ABh
Clinical Pathogens
Producers
Environ-mental
VVE
H
A
X
Y
Z
VVE strains have recently been isolated from patients across Canada. They have high level resistance that evolves after vancomycin administration and include wound isolates
VVE Normally a deletion in vanRS results in sensitivity because the cluster is turned off. In these strains a reversion was occurring under selective pressure (ie. treatment). Additional rearrangements in the region upstream HAX allows for expression of the cluster and restoration of constitutive resistance.
15
Why is this important?
Number of Antimicrobial NDA = 1
Stewardship and alternate infection control strategies are of equal importance to new drug discovery
No new antibiotics, resistance rising
16
We have a lot left to learn
On June 26, 2000 the first draft of the human genome was sequenced the project started in 1990
2001
Canadian microbiologist Dr. Julien Davies quickly pointed out: Our existence is dependent on bacterial speciesliving in and on us!
Microbiologist Dr. Joshua Lederberg coins the term microbiome
17
We have 10x more bacterial cells than human cells in our bodies that contribute to our health and homeostasis
Today we can sequence a genome in days.
17
Considerations
Antibiotics and subsequent resistance are natural phenomena
Microbes can adapt quickly
Antibiotics impact the healthy microbiome and select for resistance in human pathogens
Alternate strategies are desperately needed
So Why am I here?
What does this have to do with wound care?
19
The Microbial Influence on Healing
20
Colonization
Contamination
Critical Colonization
Infection
Wounds become chronic and stuck in an inflamed state
Haemostasis
Inflammation
Proliferation
Remodeling
Increasing clinical problems
Vigilance required
Intervention required
Note: Localized infection may or may not be accompanied by the classical signs and symptoms of inflammation
-clinical signs both visual and olfactory (smell)
Culturing yields 60% of human infections involve biofilms
In these cases the biofilm provides for a constant inoculation of the infectious organism. The result is cycles of infection.
VLU Polymicrobial Biofilm?
29
T=0
D1
W1
W2
W3
W4
T=0
W2
W3
D1
43 yr old male with a recurring chronic leg wound (5-8 yrs).
Liver disease, PVD
Prior to study was dressed with nanocrystalline Ag
Bacterial Genera: >35
At onset: >80% S. aureus
W4: Reduced to 23% relative abundance in tissue swabs
Within one week there were improvements to wound measurements. As the wound started to close there is an overall increase in diversity which is consistent with literature and shift towards healthy microbiota/skin. S 24 hrs was 14% streptococcus and primarily betaproteobacteria (comamonadaceae). By week 4 he had 23% saureus, 20% caulobacter (alphaproteobacteria), 40% betaproteobacteria, + low abundance other stuff in swabs. Debridement at week 4 was 93% saureus.
Venous arterial disease? Venous pulmonary disease
29
Microbial composition in wound swabs
Corynebacterium sp.S8-1S8-2S8-3S8-4S8-5S8-60.04364447276202610.00.0003016591251885370.00.00.00211608222490931Paenibacillus sp.S8-1S8-2S8-3S8-4S8-5S8-60.02994584262503980.00.0007541478129713420.0003859141341051610.0009099181073703360.0123941958887545S. aureusS8-1S8-2S8-3S8-4S8-5S8-60.8388021662949980.02135374697824330.8096530920060330.3908345393150020.6712920837124660.234280532043531Streptococcus sp.S8-1S8-2S8-3S8-4S8-5S8-60.03775087607518320.1424254633360190.1298642533936650.6057887120115770.05197907188353050.00574365175332527Finegoldia sp.S8-1S8-2S8-3S8-4S8-5S8-60.002070723160242110.0006043513295729250.004524886877828059.64785335262904E-50.000568698817106460.0Peptoniphilus sp.S8-1S8-2S8-3S8-4S8-5S8-60.01497292131251990.00.003469079939668170.0002894356005788710.00.0Family CaulobacteraceaeS8-1S8-2S8-3S8-4S8-5S8-60.001752150366358710.1259065269943590.01085972850678730.001350699469368070.06380800727934480.204050785973398Family BradyrhizobiaceaeS8-1S8-2S8-3S8-4S8-5S8-60.0003185727938834020.004230459307010470.0007541478129713420.00.002161055505004550.00755743651753325Family RhodospirillaceaeS8-1S8-2S8-3S8-4S8-5S8-60.00.003424657534246570.00.00.00.0Sphingomonas sp.S8-1S8-2S8-3S8-4S8-5S8-60.0003185727938834020.01933924254633360.0003016591251885370.00.01057779799818020.0256952841596131Family BurkholderialesS8-1S8-2S8-3S8-4S8-5S8-60.001433577572475310.0646655922643030.002714932126696830.00.007961783439490440.0377871825876663Family ComamonadaceaeS8-1S8-2S8-3S8-4S8-5S8-60.006690028671551450.1712328767123290.00814479638009059.64785335262904E-50.05721110100090990.178657799274486Curvibacter sp.S8-1S8-2S8-3S8-4S8-5S8-60.006690028671551450.1706285253827560.01357466063348429.64785335262904E-50.06289808917197450.17503022974607 Family ComamonadaceaeS8-1S8-2S8-3S8-4S8-5S8-60.006690028671551450.2512087026591460.007843137254901960.00.05527752502274790.107920193470375
Relative abundance (%) per sample
Biofilms in Wounds
30
Wound biofilms are often not detected.
They are intrinsically antibiotic resistant but can be caused by multi-drug resistant organisms
They may be caused by previously unknown pathogens or skin commensals (more research is needed)
Depending on the wound systemic antibiotics may not even reach the site of infection and have collateral damage to beneficial microbes
The biofilm acts as a continual source of re-inoculation
Duplantier and van Hoek. 2013. Front. Immunol. Doi:10.3389/fimmu.2013.00143
Where do we go from here? focus on wound care
Start testing antimicrobials against biofilm populations
Try other antimicrobials: metals are showing promise at eradicating biofilms and persister cells:
Antibiotics are directed toward a handful of targets, cells may not grow, but they dont die
Persister cells are not as susceptible
Multidrug resistance easily developed
Metals have multiple targets in the cell (non-specific biocides)
Biofilm tolerance is time dependent
VS
Metals
Antibiotics
Antimicrobial Silver
32
Phoenicians Water purification
Hippocrates healing and anti-disease
Silver sutures and foil used in surgery
Golden Era of Antibiotic Discovery
Emergence of antibiotic resistance
1000 BCE
400 BCE
1500-1895
1940-70
1980-now
1900-20
Widespread use of silver in medicine
Resurgence of silver usage
Silver used in surgery from the 1500s Ambrose Pare and later William Halsted used silver sutures and silver foil for surgical wounds. Go through timeline. Lead into use of silver in wounds.. This is important because.. Next slide.
32
Silver has many targets
33
OUT
IN
Gram (-)
Gram (+)
SH
Ag+
Ag+
Ag+
Ag+
Morones-Ramirez et al. 2013. Sci. Trans. Med
As a reminder, the mechanism of action of silver ions is by scavenging electrons from the bacterial cell. I like to think of electrons as the currency of a cell, driving biochemical reactions and metabolism to generate energy and go about daily business. In this way, silver ions act as an oxidizing agent.
James Collins lab at MIT published a really nice paper in 2013 detailing specific pathways that are most susceptible. This study, and most in the literature use silver nitrate as a source of silver 1+ ions.
Binding thiol groups causing protein misfolding
Misfolded proteins are translocated to the outer-membrane
Disrupt iron homeostasis including Fe-S clusters
Causes an increase in intracellular Fe2+
Stimulate superoxide production driving Fenton chemistry
Interrupt the TCA cycle driving ROS production
33
Basic Redox Chemistry
e-
e-
e-
e-
Reducing Agent
Oxidizing Agent
Red gains electrons, becoming reduced
Blue loses electrons, becoming oxidized
Oxidized
Oxidized
Reduced
Reduced
Propensity to reduce, i.e. opposite of oxidation. The addition of electrons to a compound, while oxidation is the removal of them.
Use prior slides as an example of serial oxidation
34
Silver Science: Redox Potential
35
Reduction potential
(+) potential (V)
= need for electrons
oxidation
All silver species are different
Potential to take electrons
ReactionReduction Potential (V)Ag3+ + e Ag2++ 1.80Ag2+ + e Ag++ 1.98Ag2O + 2H+ + 2e 2Ag0 + 2H2O+ 1.17Ag+ + e Ag0+ 0.80Ag2SO4 + 2 e- 2Ag + SO42-+ 0.64Ag2O + H2O + 2e 2Ag0 + 2OH-+ 0.34AgCl + e Ag0 + Cl+ 0.22Reactivity
Because silver ions are an oxidizing agent that means they participate in redox reactions. A review of reduction potentials, the higher the potential the stronger the affinity for electrons. If we look at this chart of reduction potentials silver 1+ sits here at 0.8 whereas silver in the 2+ and 3+ oxidation states have reduction potentials close to 2. For reference, hydrogen peroxide has a similar reduction potential. This means that different chemistry is accessible to Ag2+ or 3+ ions compared with Ag1+. Higher oxidation states of silver are therefore more reactive and unstable because of the need to fill their electron shells. However, we are able to stabilize these ions with oxygen as silver oxysalts.
Highlight Ag20 and the OH increase
35
AgCl
Very insoluble (1.9mg/L) and stable ie. does not react with water
Ag+(aq) + Cl-(aq) AgCl(s)
Light exposure causes degradation to metallic silver (no activity) and chlorine.
Mostly used in photography
Ag2O formed by surface oxidation of Ag metal
Releases Ag+
Ag2O(s) + H2O(aq) Ag(OH)2-(aq)
OH- causes pH spike = pain
High [Ag] needed for efficacy
O2
O2
O2
Ag
Ag
Ag2O
Ag2O
Ag Found Commonly in Dressings
Ag7NO11
37
Ag+, Ag2+, Ag3+
Here you are seeing silver oxysalt crystals. They are stable until they come into contact with an aqueous environment like a wound where they begin to degrade and release silver in the 1+, 2+ and 3+ state. The inset is a picture of the crystals after exposure to water, you can see that it looks fuzzy as it begins to degrade and release silver into the fluid. So now that the chemistry lesson is over, Im sure everyone is wondering do they actually kill bacteria?
37
Adapted from the respective product documentation/marketing materials
Spina, Carla J., Lischuk, David, Motta, Glenda, Silver Dressings 101: Silver Science
38
Silver TypeOxidation StateSilver in Dressing (mg Ag/100 cm2)Silver Release (4h in SWF)Silver Oxysalts Ag3+, Ag2+, Ag1+40107Metallic Silver, Silver (I) Oxide Ag1+, Ag016028Metallic SilverAg1+, Ag04405Silver Na H Zr Phosphate Ag1+2104Silver Sulfate Ag1+12018Silver Chloride Ag1+1228Silver Wound Dressings how to choose?
And taking a closer look at silver dressings available on the market, it is clear to see that there are not only many options for silver wound dressings, but indeed, many types of silver within those dressings. Each type of silver offering different oxidation states, different concentrations of silver and therefore different release profiles in a simulated wound fluid.
Refer to the CIT
Silver Availability
Explain how silver release (solubility) influence bioactivity. Notice difference between silver sulfate and oxysalts. Same release but different activity because of oxidation state. Wanted to examine this more closely. Surprisingly there werent any comprehensive studies looking at the differences in antimicrobial efficacy of difference silver compounds and formulations. Most of the work is done on wound dressings, in different physical formats, concentrations and quite frankly poorly designed studies. I wanted to go right to the basics and look at pure compounds for things as simple as MIC.
39
Efficacy of Silver Dressings
40
Adapted from Seth et al. 2015. Wound Repair and Regeneration DOI: 10.1111/wrr.12232
106 cfu/mL
72 hrs., 250 rpm, 37C
Rinse gauze 3X with sterile saline
Simulated Wound Fluid
+/- Nutrient Agar
Treatment (4 hrs)
SEM - S. aureus biofilm on gauze fibers
10 M
1 M
10 M
10 M
SEM P. aeruginosa biofilm on gauze fibers
20 M
10 M
200 M
200 M
Need a more clniically relevant model. We adpated a model by which biofilms are grown on standard cotton gauze fibers. Essentiall explain assay and results.
After 24 hrs the counts were below the limit of detection for both dressings.
We repeated this assay but incubated the treatments on a nutrient agar plate instead of saline and next slide
BC= Benzalkonium Chloride
40
Not all Silver Bullets are the Same
AgCl
4 hr exposure on complex media
4 hr exposure in saline
41
In Vitro In Vivo Efficacy
Burn Wound Inoculated with P. aeruginosa
Ask Questions!
What was the test method?
What was being measured?
What kind of environment was the dressing tested in?
What is the type and quantity of silver?
Are there other components that reduce bioburden or keep the wound bed healthy?
What is the construction of the dressing?
Explain data and how relevant it is.
42
Clinical Case Study #1
43
T= D4
W1
W2
W3
72 yr old male with a recurring DFU
Type II diabetic, renal failure, overweight, immunocomprimised
Insulin, steroids, anticoagulants, oral hypoglycemics
Prior to study was dressed with nanocrystalline Ag
Dressing was changed 2x weekly at home
Bacterial Genera : >50
At onset: High abundance of Staphyloccocus sp. and Paenibacillus sp. W3: Staphylococcus sp. reduced to 50% by day 4 (picture not shown)
Data is still preliminary and still in process of analyzing.
43
Microbial composition in wound swabs
Actinomyces sp.S7-2S7-3S7-4S7-50.00.00.01899659035557720.0231788079470199Corynebacterium sp.S7-2S7-3S7-4S7-50.00.001200480192076830.004870920603994150.0231788079470199Paenibacillus sp.S7-2S7-3S7-4S7-50.7283802333562110.0007202881152460980.02362396492937160.086644591611479Macrococcus sp.S7-2S7-3S7-4S7-50.06850549073438570.00.001461276181198250.0Staphylococcus sp.S7-2S7-3S7-4S7-50.1885295126973230.00144057623049220.001461276181198250.0S. aureusS7-2S7-3S7-4S7-50.00.0002400960384153660.02532878714076960.0132450331125828Anaerococcus sp.S7-2S7-3S7-4S7-50.00.00.2118850462737460.241721854304636Finegoldia sp.S7-2S7-3S7-4S7-50.00.00.2211397954213350.189293598233996Helcococcus sp.S7-2S7-3S7-4S7-50.00.00.3957622990745250.322295805739514Peptoniphilus sp.S7-2S7-3S7-4S7-50.00.00.07038480272771550.0607064017660044Caulobacteraceae familyS7-2S7-3S7-4S7-50.0005576527110501030.1906362545018010.004383828543594740.00386313465783664Sphingobium sp.S7-2S7-3S7-4S7-58.57927247769389E-50.01320528211284510.00.0Burkholderiales orderS7-2S7-3S7-4S7-50.0003860672614962250.06698679471788710.0002435460301997080.00551876379690949Comamonadaceae familyS7-2S7-3S7-4S7-50.004461221688400820.2513805522208880.003653190452995610.0022075055187638Curvibacter sp.S7-2S7-3S7-4S7-50.003345916266300620.2391356542617050.0007306380905991230.00275938189845475Roseateles sp.S7-2S7-3S7-4S7-50.004675703500343170.1800720288115250.005358012664393570.00386313465783664
Relative abundance (%) per sample
Clinical Case Study #2
44
66 yr old male with a recurring DFU (several yrs)
Type II diabetic , diabetic neuropathy, metabolic disorder, poor perfusion, overweight
Osteomyelitis and awaiting tendon surgery
T=0
W2
W4
W1
W3
T=0
W1
W2
W4
D1
W3
44
Microbial composition in wound swabs
Staphylococcus sp.S5-1S5-2S5-3S5-4S5-5S5-60.002655035084392190.00.0003344481605351179.38350380031905E-50.0008425487098472880.00225443753210433S. aureusS5-1S5-2S5-3S5-4S5-5S5-60.04911814906125540.4112874779541450.5722408026755850.05386131181383130.04560294892048450.0480851549569088Streptococcus spS5-1S5-2S5-3S5-4S5-5S5-60.8511283899108670.4566137566137570.3784280936454850.5487473022426570.9046866771985260.940614120198619Anaerococcus spS5-1S5-2S5-3S5-4S5-5S5-60.01232694860610660.0005291005291005290.001672240802675580.03650182978324110.006003159557661930.00025683465555619Finegoldia spS5-1S5-2S5-3S5-4S5-5S5-60.004361843352930020.000176366843033510.001170568561872910.006756122736229710.004212743549236440.00025683465555619Helococcus sp.S5-1S5-2S5-3S5-4S5-5S5-60.002655035084392190.00370370370370370.003344481605351170.01604579149854560.002948920484465510.000114148735802751Peptoniphilus sp.S5-1S5-2S5-3S5-4S5-5S5-60.001327517542196090.001058201058201060.001003344481605350.008820493572299890.003159557661927330.000114148735802751Allobaculums sp.S5-1S5-2S5-3S5-4S5-5S5-60.000189645363170870.00.00.00.02.85371839506877E-5Caulobacteraceae sp.S5-1S5-2S5-3S5-4S5-5S5-60.00.00.00.00.0004212743549236440.000228297471605502H. parainfluenzaeS5-1S5-2S5-3S5-4S5-5S5-60.0732031101839560.1261022927689590.0401337792642140.324106221263020.0307530279094260.0032532389703784
Relative abundance (%) per sample
Wound size over time
T=0W1W2W3W40.480.80.50.880.91
Wound Size (cm2)
45
Silver Wound Dressings
Silver dressing on the market today have different types of silver.
Most products offer Ag0 or Ag1+
New products offer Ag2+ & Ag3+
Silver Dressings are Used To:
Prevent - where there is a high risk of infection in:
Contaminated wounds
Partial- or full-thickness burns
Large and/or deep wounds
Reduced healing because of patient-related factors
Restore Wound Balance - where there is increased bioburden:
local infection
local infection that is associated with a widespread (systemic) infection
And amid all the options of silver dressings available on the market today, it is important to know that those dressing contain different types of silver and those types of silver have very different chemical properties, each playing a significant role in how the dressing as a whole, manages bioburden.
45
Additional Considerations
Infected wounds may require additional interventions such as systemic antibiotics (oral or intravenous), dressing selection to support moisture balance and debridement of necrotic tissue.
The wound management team, including the patient, must have clearly identified endpoints (goals or outcomes) with rationale for all decisions related to wound care.
46
Keeping in mind that it is also important for clinicians to recognize that topical therapies may be only one part of a complete treatment plan and all members of the team must be on the same page to ensure a collaborative treatment plan is in place and appropriate for a particular patient.
46
Summary
Systemic antibiotics might not be effective even in the absence of a resistant microbe Antibiotic stewardship is critical
Many if not all chronic wounds have a multi-species biofilm established with intrinsic antibiotic resistant
The patient may have co-morbidities significantly impacting healing
We still have a lot to learn about the influence of microbes on healing pathways
The wound team is multi-disciplinary
Innovative treatment strategies start with you
47
You might not see the biofilm
47
Instrumental Policy & Clinical Practice Documentation
Wound Infection in Clinical Practice An International Consensus (2008) http://www.woundsinternational.com/clinical-guidelines/wound-infection-in-clinical-practice-an-international-consensus
International Consensus - Appropriate Use of Silver Dressings in Wounds (2012) http://www.woundsinternational.com/clinical-guidelines/international-consensus-appropriate-use-of-silver-dressings-in-wounds
A Closer Look at Silver A Clinical Information Tool (CIT) to help you to help you choose the right silver wound dressing for your patient (2013) https://www.scribd.com/doc/261794917/Clinical-Information-Tool-a-Closer-Look-at-Silver
48
Based upon published consensus materials and personal interactions with the wound care community we have built an understanding of what and when silver wound care dressings are needed. Instrumental consensus documents and clinical information tools are challenging clinicians to re-examine clinical practice of wound care and the use of antimicrobial silvers in treatment
Thank-You
49
The Canadian Wound Care Community
Michele Suitor
Jane Ratay
Marlene Varga
Dr. David Keast
Heather Orsted (and eQuadra Solutions team)
Collaborators
Dr. Andrew Myles
Dr. Raymond Turner
Dr. Joe Lemire
Dr. Ben Willing
Dr. Mi Zhou
Westview Health Center Wound Clinic
Alberta Provincial Microbiology Lab
Exciton Technologies Inc.
Steven Miller
Deanna Pepin
Dr. Imran Ul-Haq
Karen Cuvelier
Melanie Ussyk
Rod Precht
49
Questions and Discussion
50
Supplementary
51
What about Biofilms?
52
Ag can exist with different oxidation states and aqueous availability
Ag2+/3+ has antimicrobial and antibiofilm activity at lower concentrations than Ag1+ in vitro
Planktonic populations of I) E.coli (JM109), II) P. aeruginosa (PAO1), and III) S.aureus (ATCC 25923)
24h established biofilms grown for 24h in SWF and then treated with varying concentrations of Ag compounds for 24h. n 4 SD. v
What we found explain
Focus on equivalent silver concentrations and the signifcant difference between oxysalts and
10 uM = 1 ppm
40uM = 4.3 ppm
246 uM = 28 ppm
52
50 patients, mixed etiology wounds
25 men and 25 women
Median/Avg. Age = 67 years
range 33-95 years
Median wound duration 3.5 months
Range, 2 days to 24 months
Wound treatment with exsalt SD7 weekly, minimum 4 weeks, with BWAT wound scores, analogue pain scale, and cost analysis.
Spina, C.J., Lischuk, D.L, CE Mark Technical File: Scientific and Clinical Report. Exciton Technologies Inc., December 2011, In Support of European Regulatory Submission
Wound statistics for the 49 patients enrolled in the multi-site study evaluating novel silver oxysalts wound dressing. Statistics Chronic(n=44)Non-Chronic (n=5)Mean age (years SD) 64 2074 16Median age (years [range]) 65 [95]79 [38]Mean wound duration (months SD) 3.7 4.90.5 0.3Median wound duration (weeks [range]) 2.0 [24.0]0.5 [0.7]Mean BWAT at Start ( SD) 35 826 5Median BWAT at Start [range] 33. [31]25 [14]Mean BWAT at End ( SD) 19 1219 40Median BWAT at End [range] 9.2. [0.4]9 [1]53
Clinical Performance
To further support our scientific knowledge, in-vivo research was initiated by way of clinical case studies. In one of our studies, a series of 50 patients with mixed chronic and acute wounds was evaluated with exsalt dressings weekly over a minimum of 4 weeks or at the instruction of the physician.
Although the therapeutic goal of antimicrobial dressings is to provide a protective barrier and to control the bacterial burden levels in the wound environment. It is important to properly assess the progression of wound healing and key signs of infection and bacterial balance to accurately evaluate the performance of these dressings. Therefore in this study, periodic wound assessment in addition to pain assessment and cost analysis was completed to determine the impact of silver oxysalt wound dressings on these diverse wounds.
54
Day 0
Day 6
Day 16
patients entered (4 week) study with
chronic (non-healing) wounds
93% of patients perceived a reduction in pain (with no pain reported upon dressing application)
98% of wounds had a decrease in wound exudate
25% of wounds healed within the 4 week evaluation
48% cost savings observed over standard of care
Conclusion:
Higher oxidation state silver (in Exsalt wound dressing) is effective for chronic and critically colonized wounds.
Data on file - GMA Multi-Site Study
Multi-Center Clinical Evaluation
Mixed Etiology Case Series
20 Patient case series*
10 Chronic Leg Ulcers
10 Chronic Foot Ulcers
Positive outcomes
Size in 16 out of 20 stalled chronic wounds
Decrease in cumulative pain scores
Patricia Coutts, Grace Modelski, Laurie Goodman, Judy Ryan, R. Gary Sibbald M.D.
* 20 out of 30 total patients analyzed to date
Chronic Wound Case Series
6 Patient case series*
Mixed etiology
Localized infection or at risk of infection
Exsalt SD7 applied twice weekly for four weeks
Positive outcomes
Reducing wound size: 52.3 cm2 to 34.1 cm2
Visual improvement in bacterial burden
Decrease in exudate
Symptom# ImprovedPain6Oedema6Stalled Healing5Malodor5Bakeer M, Vair A, Keast D, Evaluation of Silver-impregnated Dressings in a Clinical Setting: Observations on Efficacy and Practicality, CAWC 2012
Microbial Ecology of Wounds
57
V1
Swab
Debridement
V2
Week1
Week2
Week3
Week4
Dressing Change
V3
V4
V5
V6
Day 1
T=0
INCLUSION AND EXCLUSION CRITERIAInclusionExclusionAge >17 yrsSystemic antibiotics in previous 2 weeksChronic non-healing wound > 6 wkKnown skin sensitivity Requires at least weekly careParticipation in another studyV1
Westview Health Center, Stony Plain, AB
Debride wound collect
Swab surface of wound
Extract total DNA
Amplify 16S rDNA gene
NGS 454 platform
Briefly the study is.
57
Diabetic Foot Ulcer
58
November, 2013: Started on Acticoat Flex
December, 2013: Switched to promogram
January, 2014: Restarted on Acticoat Flex because wound got worse
Mid Jan, 2014: Promogram added to Flex
February 12, 2014 - Started on Exsalt
March 13, 2014 Beginning to Epithelialize
Feb. 20, 2014
exsalt cut to size, foam secondary dressing
Bacterial Genera : >10
High proportion of streptococcus on all visits. From tissue swabs 92% relevant abundance from T=0 (before exsalt application) to 41% relative abundance on week 4 of exsalt treatment.
Note: Debridement samples have an inverse correlation to streptococcus (assuming dead slough). DNA analysis does not indicate live/dead cells.
Patient suffers from: Type I diabetes; morbidly obese; CAD; PVD, Diab neuropathy,
Both SD7 and T7 were used on this wound.
Patient 3
58
Infected Surgical Wound
59
Exsalt SD7 fan-folded and packed into wound.
Week One: the wound decreased 70% in size.
Week Three: switched to T7 for packing
Secondary dressing changed according to level of exudate
Patient 2: Morbidly Obese, Hypertension, Depression, Anemia
Non-adherence to treatment plan, immunocompromised and poor lifestyle choices
Treatment in clinic began November 5, 2013, on exsalt February, 2014 had a hole in bowel and required surgery.
59
Right Flank
60
Prior to study treated with Hydrofera Blue
Treated with exsalt T7 and secured with film (eg. Tegaderm)
Healed before week 2 visit.
Day 10: Wound healed
Fragile skin, wound caused by cell phone rubbing against leg
Patient 4: Burn at 3 years of age-caused kidney crystalization and thus kidney stones, has had many lithotrypsies, hemachromatosis 2ndary polycythemia
60
Non-Healing VLU
61
Day 0, pre- exsalt application
Day 1 Jan 28, 2014
Week 2
Week 4
December 4, 2013: Started on Aquacel Ag + Mepilex
December 12, 2013: NU-GEL + Alldress
December 19, 2013: Biopsy taken, NU-GEL, calcium alginate, Alldress
January, 2014: Mepilex Ag and coban wrap
Wound fully healed on next follow up visit
Bacterial Genera: >25
Before treatment: Mostly betaproteobacteria (Comamonadaceae)
W4: Mainly Allobaculum and Caulobacter (associated with skin).
Patient 1 was on other silver dressings for 8 weeks before switching to exsalt.. Healed within 4 weeks.
61
Foot Wound - PVD
62
Day 0, pre- exsalt application
Day 2
Week 2 - Healed
Patient comments: Wound less painful and happy with improvement
Dressing treated with Inadine (iodine antimicrobial) prior to exsalt study)
Patient 6
62
Recurring Cellulitis
63
Patient had an infection to the lower leg, after treatment with exsalt a notable improvement to periwound skin was observed (breakdown was occurring).
Patient 9: Cannot do visit 2 because of compression wrap. small area noted to crease anteriorly at ankle and foot. Mepilex lite to both feet. Infection to lower leg as breakdown(periwound worse), odor to lower leg to be assessed by dr. june 4. healing rate is 26.7 % since 20/may; dr. said no antibiotics on june 4, periwound is better exsalt lightly packed, ichthopaste to calf wound.
63
Incisional Hernia skin graft
64
Pre-study: Hypergranulation, dressed with Biatain Ag
Purulent discharge ceased by week 2
Exsalt packed into undermining and dressed center of wound
Week 3
Week 4
Week 2
Day 0
Patient 10: pain tender with packing in undermining. One large piece to undermining, one small to edge of undermining, one small to center of graft. Prior to visit on Biatain Ag nothing to debride on visit 3 . Hypergranulation until day 3 then just granulation tissue, wound is starting to look healithier.
64
Recurrent Venous Stasis Ulcer failed graft
65
Week 1
Day 0
Week 2
Week 4
Pre-study: On Acticoat flex
Wound measurements improving
Increase of granulation
Continued improvement, wound eventually closed
Patient 13: What happened unti now? was on acticoat flex prior to study and stopped oral antibitics 5 days earlier (may 21) on visit 3 SD7 was fenestrated to allow exudate through stinging a short time; wound measurements improved on visit 4 and 5 hypergranulation occuring so switched to T7 pain on debriding and cleaning; some hypergranulation now follow up? wound improvments Completed study now was exsalt still on the last week? wound healed august 11, outcomes completed. Wound shrunk by 50%
65
Fistula infection 1 month post surgery
66
Day 0
Week 4
Day 0 - 1 month post surgery. Wound epithelializing by week 2, healed by week 4.
Patient 14; 74 yr old F
66
Recurrent VLU
67
Day 0
Week 1
Week 2
Week 3
Week 4
Patient 15: failed graft site
Not sure the outcome here. The wound actually increased in size but might be the case of getting worse before getting better.
67
Questions?
68
68
O O
NHHN
ONH
OHN
ONH
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NH
O
HO
HO
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OHHO O
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Cl
ClO
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NH2
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OHOH
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CH3
NH2HOHO
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Vancomycin Teicoplanin
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Dalbavancin Telavancin
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HN
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N
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H2N NH2
H2N
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Penicillin Streptomycin
Ag7NO11
Nanocrystall
ine Silver Ag2SO
40
10
20
30
40
200400600
4 hr silver release into RO H2OSi
lver
rele
ase
(ppm
) ppm Ag+/dressing
ppm Ag+/mg Ag(s)
A
g
7
N
O
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a
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10
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400
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4 hr silver release into RO H
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(
p
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ppm Ag
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ppm Ag
+
/mg Ag
(s)
0 24 48 72 96 120 144 168 1920
100
200
300
400
500
600
Time (hrs)
Silv
er re
leas
e (p
pm)
Cumulative Ag+ Release from Ag7NO11
024487296120144168192
0
100
200
300
400
500
600
Time (hrs)
S
i
l
v
e
r
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(
p
p
m
)
Cumulative Ag
+
Release from Ag
7
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Ag7NO11 Ag2SO
4
Negative Co
ntrol1
10
LOD
4
8
2
Log
10 v
alue
[cfu
/mL]
MRSA 4 hr Log Reduction
A
g
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1
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MRSA 4 hr Log Reduction
Ag Oxysa
lts Wound
Dressing
HF Ag/BC
/EDTA
HF Ag
Nanocrys
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tive0
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log
cfu/
gauz
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P.aeruginosa (blavim-2)
***
****
****
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P.aeruginosa (bla
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***
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P. aerugin
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4
6
8
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log
cfu/
gauz
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****
Ag Oxysalts Wound DressingHF Ag/BC/EDTAHF AgNegative
************
*
P
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Ag Oxysalts Wound Dressing
HF Ag/BC/EDTA
HF Ag
Negative
****
********
*
Ag 7NO 1
1 Pow
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Ag 7NO 1
1 Dre
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AgCl/BC
/EDTA
Nanocr
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SSD (+)
contro
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Negativ
e
Baselin
e0
5
10
LOD
Log
10 v
alue
[cfu
/mL]
Porcine Burn Biofilm Model
A
g
7
N
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1
1
P
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A
g
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L
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c
f
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]
Porcine Burn Biofilm Model
AgNO3
Ag2SO4 Ag2O
Ag Oxysa
lts0
10
20
30
4050
450
850
1250
Con
c. o
f Met
al [
M]
Minimum Biofilm Eradication Concentration Established Biofilms - 24 hr Treatment
E.coliP.aeruginosa
S.aureus*
****
*
*
*
A
g
N
O
3
A
g
2
S
O
4
A
g
2
O
A
g
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s
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10
20
30
40
50
450
850
1250
C
o
n
c
.
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f
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e
t
a
l
[
m
M
]
Minimum Biofilm Eradication Concentration
Established Biofilms - 24 hr Treatment
E.coli
P.aeruginosa
S.aureus
*
*
*
*
*
*
*
*
AgNO3
Ag2SO4 Ag2O
AgOxysa
lts0
20
40
60
80
500
1000
1500
2000
Con
c. o
f Met
al [
M]
Minimum Biocidal Concentration4 hr exposure to Ag
E.coliP.aeruginosa
S.aureus**** ****
****
***
A
g
N
O
3
A
g
2
S
O
4
A
g
2
O
A
g
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l
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20
40
60
80
500
1000
1500
2000
C
o
n
c
.
o
f
M
e
t
a
l
[
m
M
]
Minimum Biocidal Concentration
4 hr exposure to Ag
E.coli
P.aeruginosa
S.aureus
****
****
****
**
*
Wound Scores
27
29
31
33
02468
Time (weeks)
Avg. BWAT Score
Pain
26
30
34
38
42
02468
Time (weeks)
Cumulative Pain Scores
Chart40248
Average Scores
Time (weeks)
Avg. BWAT Score
Wound Scores
32.55
30.5
29.75
28.3529411765
Patient InfoComorbiditiesDMDiabetes MellitusLDLiver
DiseaseObObesitySmSmokingHCHypercholestriaPVDPerpheral Vascular
DiseaseHLHyperlipidemaAngAngioplastyVIVenous
insufficiencyBWBilateral WoundsHTHypertensionTIATransient Ischemic
AttackTDThyroid diseaseSASleep
ApneiaPatientSummaries1234567891011121314151617181920IDAvgStdevMeanRangeM-012L-001L-014L-004L-008L-011L-017L-019M-006M-009M-010L-020M-005M-007M-016M-002L-018M-015M-003L-013Age56.812.955.050.05546524658497574316255674550496376445781sexmale16female4malemalemalefemalemalefemalemalemalemalemalemalefemaleMalefemaleMaleMalemaleMalemalemaleheight6'1"5'4"5'6"6'5"6'5'8"5'7"5'10"wt
(lbs)285335165290200
lbs230189200WoundFootLegLegLegLegLegLegLegFootFootFootLegFootFootFootFootLegFootFootLeglocationleft
4th medialright lateral legright medial ankleright lateral legrt
leg pretibialLeft med. Legleft malleolusleft leg ulcerleft heelrt
1st met heelrt 1st toert leg melleolusfirst metatorsal sheelleft
second met heelleft 5th met heelleft 1st toeleft med leg
malleolusleft 2nd met heelrt 5th met heelrt met malleolusduration
(mo)22.214.824.058.0524362424123624121222424910122448601
causeneruopathyvenous stasisvenous statsis ulcerVSUnecrobiosis
lipoidiciasurgeryVSvsupressure from
braceneuropathyneuropathyvsuNeuropathypressureneuropathydiabetic
neuropathic ulcerVIneuropathyneuropathicVSU2
causediabetesvenoustraumaV-HTdiabetesVSUVHTvs dieasespina
bifidadiabetesdiabetesvenous diseasediabetesneuropathynerve damage
(trauma)diabetesleined five
factorDiabetesdiabeticVHTComorbiditiesDM, O, HC, HL, VI, HTDM, Ob,
VIVI, car accident, broken femur, ABPI 1.08TD, LD, HTDM, HC/HL, Sm,
PVD, VI, HT, Ang, BWVIDM, HC/HL, VI, HT, two wounds on left
melleous Top wound = 1.9 x 1.0 lower wound = study woundHC/HL, VI,
HTspina bifida,DM, VI, TIA, SADM, HC/HL,TD,HTHC/HL, TD, VI, HT- apr
25th Toe 0.76 ABI 109 R leg 1.10,158DM, VI, decreased hearing in
right ear, ABPI = 1.12Ob, TD, malignant ashma, uteral cancer
(4years ago)HC/HL, VI, HT, wound @left toe, 2002 nerve damage, hip
fracture, high urinic acidDM, VI, HT,VI, rt leg med malleolus ulcer
0.2 x 0.2DM, Wound left footDM, HC/HL, VI, Renal failure (on
dialysis over 600 creatinine) Diabetic neruopathy (ABPI L=0.92
R=0.87)HC/HL, TD, HT, wounds on both legs, Rt med/L lat, ABPI
1.23medicationsMetformin, metoprolol, fluosemide 40,20, Asparin 81
mgmetformin, COQ10, Zn-Cu balance, probiotic 90, prion, acticoat
flex, antibioticsDoxycillinTrentolwortin, trentol, docycycline,
crestor, adolot, diovon, vit diolene,
compressionpitropenMetroprolol, tartrate, metformin, vit B12,
amlodipihe, bedulate, asprin, mazaar, diamicron, lamasilamlodipine,
asprin, imolopomine, tisinophihe,lipitor, levothyroxine,
fentofibreteNew offloading shoe Jan 13th,Paxel, nortriptylini,
oxylutynine chloride, paroxtine, obesitymoxifloxin, accupri,
allopurinol, lipitorsolofelk 500 mg, metformin 500 mg, glyberide 5
mg, warfarin 2.5 mg, nifedipine 60 mg, enelopril 5 mgmoxyfloxin,
worfin, flo max, vitaminsciprofloxin, metaformin, glucosoleCalcium
oyster, phosrenol, eurflex, lipitor, recaltrol, entrophen, senoket,
relloaite, epoinect, quinine, tiemolca, rotioectosome, ciprelox,
lorazepam, nitrolinoprol sprayIrbesorten 300 mg, synthroid 0.07 mg,
amlodirinebesylate 5 mg, hydrochlorothiolsrole 25 mg, bentoxifyline
400 mg, crestor 5 mgPrevious dressings usedmefix, telfaActicoat
flex, silvercel, antibioticsActicoat burn, silvercel, acticoat,
iodosorbMesorbbetaine, inadine, telfa, mefix, Jan 24th acticoat
flex5 Dec 2011- Inadine & Mefixdec 12th 2011- betadine,
inadine, ETE, mefixNov 25 2011- inadine, mepore, allevyn/Oct 2011-
inadeine, mepore2 may 2012- inadine, ETE, mesorb
TimelineClinical TimelineIntended (days)Intended
(weeks)01428560248PatientDates (Calendar)Actual (days)Actual
(weeks)M-0122/22/123/8/123/22/124/19/12010295601.44.18.0L-0011/16/121/30/122/13/123/13/12014285702.04.08.1L-0142/27/123/12/123/26/124/27/12014286002.04.08.6L-0041/30/122/13/122/28/123/26/12014295602.04.18.0L-0082/16/122/29/123/15/124/12/12013285601.94.08.0L-0112/16/123/1/123/15/124/12/12014285602.04.08.0L-0174/19/125/2/125/16/126/13/12013275701.93.98.1L-0195/17/125/29/126/13/127/12/12012275601.73.98.0M-0062/13/122/27/123/12/124/10/12014285702.04.08.1M-0092/16/123/1/123/15/124/12/12014285602.04.08.0M-0102/16/122/29/123/15/124/12/12013285601.94.08.0L-0205/31/126/14/126/28/127/26/12014285602.04.08.0M-0052/8/122/22/123/8/124/5/12014295702.04.18.1M-0072/13/122/27/123/12/124/10/12014285702.04.08.1M-0163/23/124/5/125/17/12013285501.94.07.9M-0021/25/122/8/122/22/123/21/12014285602.04.08.0L-0181/25/122/8/122/22/123/21/12014285602.04.08.0M-0153/1/123/15/123/29/124/27/12014285602.04.08.0M-0031/25/122/8/122/22/123/21/12014285602.04.08.0L-0132/23/123/8/123/22/124/19/12014285602.04.08.0Avg0.013.528.156.40.01.94.08.1Stdev0.01.00.51.00.00.10.10.1
PainFootLegPain Description (on week)WeekTotal Change
(w8-w0)SummariesPatient02480248Change (w2-w0)Change (w4-w2)Change
(w8-w4)M-012throbbingthrobbingshootingthrobbing6.010.02.54.5-1.54.0-7.52.0L-001stingneedle1.01.01.01.000.00.00.0L-0140.00.00.00.000.00.00.0L-004tightsting
1h of dressing changepain when
walking5.07.02.58.032.0-4.55.5L-008burnburnburn0.51.00.01.510.5-1.01.5L-011sharp/stabsharp/stabsharpshooting3.02.04.04.01-1.02.00.0L-017stiffness0.00.00.03.53.50.00.03.5L-019burnbruise1.01.51.51.000.50.0-0.5M-0060.00.00.00.000.00.00.0M-0090.00.00.00.000.00.00.0M-010burnburn-
pain to
touchburn0.01.03.01.011.02.0-2.0L-020burnthrobburnprickly2.01.01.01.0-1-1.00.00.0M-005burn,
sharpburnburnclosed5.55.54.00.0-5.50.0-1.5-4.0M-007pressure,
intermitent
sharpsharp10.00.00.02.0-8-10.00.02.0M-0160.00.00.00.000.00.00.0M-002burnnail
through
toenail2.55.05.00.0-2.52.50.0-5.0L-018trobbingstiningintermittent2.51.50.50.0-2.5-1.0-1.0-0.5M-015nusencepressure0.01.01.01.011.00.00.0M-0030.00.00.00.000.00.00.0L-013stingburnburnsting1.02.54.01.001.51.5-3.0n
patients with pain12.013.012.012.00Cumulative Total
Pain40.040.030.029.598129No Change6456Decreased Pain5835Increased
PainFootPain Description (on week)WeekTotal Change
(w8-w0)SummariesPatient02480248Change (w2-w0)Change (w4-w2)Change
(w8-w4)M-012throbbingthrobbingshootingthrobbing6.010.02.54.5-1.54.0-7.52.0M-0060.00.00.00.000.00.00.0M-0090.00.00.00.000.00.00.0M-010burnburn-
pain to touchburn0.01.03.01.011.02.0-2.0M-005burn,
sharpburnburnclosed5.55.54.00.0-5.50.0-1.5-4.0M-007pressure,
intermitent
sharpsharp10.00.00.02.0-8-10.00.02.0M-0160.00.00.00.000.00.00.0M-002burnnail
through
toenail2.55.05.00.0-2.52.50.0-5.0M-015nusencepressure0.01.01.01.011.00.00.0M-0030.00.00.00.000.00.00.0n
patients with pain4.05.05.04.00Cumulative Total
Pain24.022.515.58.50121No Change4123Decreased Pain1412Increased
PainLegPain Description (on week)WeekTotal Change
(w8-w0)SummariesPatient02480248Change (w2-w0)Change (w4-w2)Change
(w8-w4)L-001stingneedle1.01.01.01.000.00.00.0L-0140.00.00.00.000.00.00.0L-004tightsting
1h of dressing changepain when
walking5.07.02.58.032.0-4.55.5L-008burnburnburn0.51.00.01.510.5-1.01.5L-011sharp/stabsharp/stabsharpshooting3.02.04.04.01-1.02.00.0L-017stiffness0.00.00.03.53.50.00.03.5L-019burnbruise1.01.51.51.000.50.0-0.5L-020burnthrobburnprickly2.01.01.01.0-1-1.00.00.0L-018trobbingstiningintermittent2.51.50.50.0-2.5-1.0-1.0-0.5L-013stingburnburnsting1.02.54.01.001.51.5-3.0n
patients with pain8.08.07.08.00Cumulative Total
Pain16.017.514.521.02133No Change2332Decreased Pain4423Increased
Pain
Pain000
Total Change over 8 weeks
Number of Patients
Impact of exsalt SD7 on Pain Scores over a total 8 week
evaluation period
NERDS-STONES0000
Cumulaive Scores
Time (weeks)
Cumulative Pain Scores
Pain
0
0
0
0
BWATFootLegNERDS Infection Signs (on week)Total Change
(w8-w0)NERDS SummariesSTONEES Infection Signs (on week)Total Change
(w8-w0)STONEES Summaries0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0121000-1-1.00.00.010021-1.00.02.0L-0011000-1-1.00.00.010021-1.00.02.0L-014000110.00.01.010010-1.00.01.0L-00421020-1.0-1.02.0010221.0-1.02.0L-0081210-11.0-1.0-1.0131102.0-2.00.0L-011000110.00.01.0011221.00.01.0L-017000110.00.01.01010-1-1.01.0-1.0L-019001220.01.01.01010-1-1.01.0-1.0M-006000000.00.00.02111-1-1.00.00.0M-009010001.0-1.00.0020112.0-2.01.0M-010000000.00.00.01000-1-1.00.00.0L-020000000.00.00.01100-10.0-1.00.0M-005010001.0-1.00.0010001.0-1.00.0M-007001000.01.0-1.0001110.01.00.0M-016000000.00.00.0111100.00.00.0M-0021000-1-1.00.00.0001000.01.0-1.0L-0181110-10.00.0-1.010210-1.02.0-1.0M-015000000.00.00.0110100.0-1.01.0M-003000000.00.00.0010001.0-1.00.0L-01310110-1.01.00.0110100.0-1.01.0n
patients with signs755613119130n patients with signsCumulative
Signs865814141017Cumulative Signs111213129678No Change55435884Signs
Decreased43356658Signs IncreasedFootNERDS Infection Signs (on
week)Total Change (w8-w0)NERDS SummariesSTONEES Infection Signs (on
week)Total Change (w8-w0)STONEES Summaries0248Change (w2-w0)Change
(w4-w2)Change (w8-w4)0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0121000-1-1.00.00.010021-1.00.02.0M-006000000.00.00.02111-1-1.00.00.0M-009010001.0-1.00.0020112.0-2.01.0M-010000000.00.00.01000-1-1.00.00.0M-005010001.0-1.00.0010001.0-1.00.0M-007001000.01.0-1.0001110.01.00.0M-016000000.00.00.0111100.00.00.0M-0021000-1-1.00.00.0001000.01.0-1.0M-015000000.00.00.0110100.0-1.01.0M-003000000.00.00.0010001.0-1.00.0n
patients with signs755656460n patients with signsCumulative
Signs22106747Cumulative Signs0000No Change2278No Change2221Signs
Decreased2384Signs Decreased0110Signs Increased3358Signs
IncreasedNERDS Infection Signs (on week)Total Change (w8-w0)NERDS
SummariesSTONEES Infection Signs (on week)Total Change
(w8-w0)STONEES Summaries0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)PatientL-0011000-1-1.00.00.010021-1.00.02.0L-014000110.00.01.010010-1.00.01.0L-00421020-1.0-1.02.0010221.0-1.02.0L-0081210-11.0-1.0-1.0131102.0-2.00.0L-011000110.00.01.0011221.00.01.0L-017000110.00.01.01010-1-1.01.0-1.0L-019001220.01.01.01010-1-1.01.0-1.0L-020000000.00.00.01100-10.0-1.00.0L-0181110-10.00.0-1.010210-1.02.0-1.0L-01310110-1.01.00.0110100.0-1.01.0n
patients with signs755613119130n patients with signsCumulative
Signs644814141017Cumulative Signs111213129678No Change55435884Signs
Decreased43356658Signs
IncreasedPatientIDM-012L-001L-014L-004L-008L-011L-017L-019M-006M-009M-010L-020M-005M-007M-016M-002L-018M-015M-003L-013Weeks0.01.44.18.00.02.04.08.10.02.04.08.60.02.04.18.00.01.94.08.00.02.04.08.00.01.93.98.10.01.73.98.00.02.04.08.10.02.04.08.00.01.94.08.00.02.04.08.00.02.04.18.10.02.04.08.10.01.94.07.90.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.0Nnon-healing111111E
exudate11Rred/bleeding111111Ddebris1111111111111SsmellTotal
NERDS10001000000121021210000100010012000001000000000001000010000010001110000000001011S
size1111111T temp1111111111111111111111111111111Oos, probeNnew
breakdown111Eexudate,1Eerhythema/edema1111111111111SsmellTotal
STONEES10021002100101021311011210101010211102011000110001000011111100101021110101001101
BWAT000000
NERDS
STONEES
Number of Patients
Impact of exsalt SD7 on NERDS & STONEES clinical signs and
symptoms over a total 8 week evaluation period
SizeFootLegBWAT (on week)Summaries0248Total ChangeChange
(w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0122733286.0-5.0L-00130343127-34.0-3.0-4.0L-014332632-7.06.0L-0043536314051.0-5.09.0L-00836393833-33.0-1.0-5.0L-01139323130-9-7.0-1.0-1.0L-017383436-4.02.0L-01936263632-4-10.010.0-4.0M-00621272620-16.0-1.0-6.0M-0092734213147.0-13.010.0M-01034283232-2-6.04.00.0L-02030292726-4-1.0-2.0-1.0M-00528292913-151.00.0-16.0M-00734282724-10-6.0-1.0-3.0M-01634282724-10-6.0-1.0-3.0M-002322828331-4.00.05.0L-01835302326-9-5.0-7.03.0M-015292726312-2.0-1.05.0M-00334262627-7-8.00.01.0L-01339364033-6-3.04.0-7.0AVG32.5530.529.7528.35294117650031No
Change1313128BWAT Decreased4756BWAT IncreasedFootBWAT (on
week)Summaries0248Total ChangeChange (w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0122733286.0-5.0M-00621272620-16.0-1.0-6.0M-0092734213147.0-13.010.0M-01034283232-2-6.04.00.0M-00528292913-151.00.0-16.0M-00734282724-10-6.0-1.0-3.0M-01634282724-10-6.0-1.0-3.0M-002322828331-4.00.05.0M-015292726312-2.0-1.05.0M-00334262627-7-8.00.01.03002882702350031No
Change1313128BWAT Decreased4756BWAT IncreasedLegBWAT (on
week)Summaries0248Total ChangeChange (w2-w0)Change (w4-w2)Change
(w8-w4)PatientL-00130343127-34.0-3.0-4.0L-014332632-7.06.0L-0043536314051.0-5.09.0L-00836393833-33.0-1.0-5.0L-01139323130-9-7.0-1.0-1.0L-017383436-4.02.0L-01936263632-4-10.010.0-4.0L-02030292726-4-1.0-2.0-1.0L-01835302326-9-5.0-7.03.0L-01339364033-6-3.04.0-7.03513223252470031No
Change1313128BWAT Decreased4756BWAT
IncreasedPatientIDM-012L-001L-014L-004L-008L-011L-017L-019M-006M-009M-010L-020M-005M-007M-016M-002L-018M-015M-003L-013Weeks0.01.44.18.00.01.44.18.00.02.04.08.60.02.04.18.00.01.94.08.00.02.04.08.00.01.93.98.10.01.73.98.00.02.04.08.10.02.04.08.00.01.94.08.00.02.04.08.00.02.04.18.10.02.04.08.10.01.94.07.90.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.0BWAT1-
size11111111122244342222212222221111111111111111111111111111111111132221111111122222-
depth33332333313333333343333333333333333233333333333233333333333333333333333333333337-
exudate
type43333444333433434524443443434144431434443443443443444344433444443344433344448-
exudate
amount44444443333444454543334444343333331343444433224434332433254444143344344444312-
granulation
tissue34323343323232223443333334344334322224445255434232323223322343353324325432343425-
necrotic tissue
type12111111212121142342111123212122111112131111111111131113111211233111111211122226-
necrotic tissue
amount1411111141412114344311114451415411111511111111111115111511141144411111151114335Infection
crit.
Total1721161515171816191320172118182521262420171617182223221821132121915149152210191916181917151613161616021161514221615142117172126201013171515192315151623212221BWAT
Total273328303431273326323536314036393833393231303834363626363221272620273421313428323230292726282929closed34282724342827243228283335302326292726313426262739364033
Size000
Total Change over 8 weeks
Number of Patients
Impact of exsalt SD7 on BWAT Scpres over a total 8 week
evaluation period
Microbio00000000000000000000222222222222222222224444444444444444444488888888888888888888
M-012
L-001
L-014
L-004
L-008
L-011
L-017
L-019
M--006
M-009
M-010
L-020
M-005
M-007
M-016
M-002
L-018
M-015
M-003
L-013
Time (weeks)
Total BWAT Score
Impact of exsalt SD7 on BWAT Scpres over an 8 week evaluation
period
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Commments0248
Average Scores
Time (weeks)
Avg. BWAT Score
Wound Scores
0
0
0
0
TurnerWound size cm3 (on week)Summaries0248Total ChangeChange
(w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0120.180.841.281.281.0930.6580.4350.000L-0010.420.540.190.11-0.310.122-0.348-0.084L-0140.580.610.650.640.0640.0360.034-0.006L-0043.893.653.544.660.776-0.232-0.1161.124L-0080.760.780.730.45-0.3080.027-0.055-0.280L-0112.860.993.956.964.098-1.8742.9643.008L-0170.4420.3640.5510.8400.398-0.0780.1870.289L-0190.2530.1900.0210.200-0.053-0.063-0.1690.179M-0060.0150.0120.0060.008-0.007-0.003-0.0060.002M-0090.0600.1680.1050.2400.180.108-0.0630.135M-0100.4500.1600.0600.036-0.414-0.290-0.100-0.024L-0200.0600.0200.0040.009-0.051-0.040-0.0160.005M-0050.8401.8000.2240.000-0.840.960-1.576-0.224M-0070.0120.0400.0720.004-0.0080.0280.032-0.068M-0160.3640.0200.0280.015-0.349-0.3440.008-0.013M-0021.5120.1820.6720.910-0.602-1.3300.4900.238L-0187.0803.0001.3720.537-6.543-4.080-1.628-0.835M-0150.1200.2000.1200.072-0.0480.080-0.080-0.048M-0030.0600.0160.0250.025-0.035-0.0440.0090.000L-0131.3260.5600.49212.00010.674-0.766-0.06811.5080002No
Change1312129Size Decrease7889Size IncreasePatient0.1presumed to
have depth due to presence of the woundWound size cm3 (on
week)Summaries0248Total ChangeChange (w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0120.180.841.281.281.0930.6580.4350.000M-0060.0150.0120.0060.008-0.007-0.003-0.0060.002M-0090.0600.1680.1050.2400.180.108-0.0630.135M-0100.4500.1600.0600.036-0.414-0.290-0.100-0.024M-0050.8401.8000.2240.000-0.840.960-1.576-0.224M-0070.0120.0400.0720.004-0.0080.0280.032-0.068M-0160.3640.0200.0280.015-0.349-0.3440.008-0.013M-0021.5120.1820.6720.910-0.602-1.3300.4900.238M-0150.1200.2000.1200.072-0.0480.080-0.080-0.048M-0030.0600.0160.0250.025-0.035-0.0440.0090.000Cumulative
Size Total3.623.442.592.590002No Change8555Size Decrease2553Size
IncreaseWound size cm3 (on week)Summaries0248Total ChangeChange
(w2-w0)Change (w4-w2)Change
(w8-w4)PatientL-0010.420.540.190.11-0.310.122-0.348-0.084L-0140.580.610.650.640.0640.0360.034-0.006L-0043.893.653.544.660.776-0.232-0.1161.124L-0080.760.780.730.45-0.3080.027-0.055-0.280L-0112.860.993.956.964.098-1.8742.9643.008L-0170.4420.3640.5510.8400.398-0.0780.1870.289L-0190.2530.1900.0210.200-0.053-0.063-0.1690.179L-0200.0600.0200.0040.009-0.051-0.040-0.0160.005L-0187.0803.0001.3720.537-6.543-4.080-1.628-0.835L-0131.3260.5600.49212.00010.674-0.766-0.06811.508Cumulative
Size Total17.6610.7111.5026.400000No Change5774Size
Decrease5336Size
IncreaseDays0102956013275701429570142856Weeks0.01.44.18.00.01.93.98.10.02.04.18.10.02.04.08.0l1.31.21.51.72.62.62.94.20.610.800.50.40.50.5w1.41.41.71.51.71.41.9211.50.400.40.40.50.5d0.10.50.50.50.10.10.10.11.41.20.700.30.10.10.10.180.841.281.280.4420.3640.5510.8400.8401.8000.2240.0000.0600.0160.0250.025L-001L-019M-007L-0131/16/121/30/122/13/123/13/125/17/125/29/126/13/127/12/122/13/122/27/123/12/124/10/122/23/123/8/123/22/124/19/1201428570122756014285701428560.01.44.18.00.01.73.98.00.02.04.08.10.02.04.08.0l3.832.41.82.31.92.12.50.20.40.60.23.944.14w1.11.80.80.61.110.10.80.30.50.60.21.71.41.23d0.10.10.10.10.10.10.10.10.20.20.20.10.20.10.110.420.540.190.110.2530.1900.0210.2000.0120.0400.0720.0041.3260.5600.49212.000L-014M-006M-0162/27/123/12/123/26/124/27/122/13/122/27/123/12/124/10/123/23/124/5/125/17/120142860014285701328550.02.04.08.60.02.04.08.10.01.94.07.9l3.63.43.83.20.50.40.30.41.30.40.70.5w1.61.81.720.30.30.20.20.70.50.40.3d0.10.10.10.10.10.10.10.10.40.10.10.10.580.610.650.640.0150.0120.0060.0080.3640.0200.0280.015L-004M-009M-0021/30/122/13/122/28/123/26/122/16/123/1/123/15/124/12/121/25/122/8/122/22/123/21/120142956014285601428560.02.04.18.00.02.04.08.00.02.04.08.0l5.86.35.86.311.21.51.51.81.41.41.3w6.75.86.17.40.60.70.70.81.41.31.21.4d0.10.10.10.10.10.20.10.20.60.10.40.53.893.653.544.660.0600.1680.1050.2401.5120.1820.6720.910L-008M-010L-0182/16/122/29/123/15/124/12/122/16/122/29/123/15/124/12/121/25/122/8/122/22/123/21/120132856013285601428560.01.94.08.00.01.94.08.00.02.04.08.0topl2.82.92.62.81.51.610.65.954.91.82.5w2.72.72.81.60.50.20.10.6432.80.91.5d0.10.10.10.10.60.50.60.10.30.20.10.10.1SUM0.760.780.730.450.4500.1600.0600.0367.0803.0001.3720.1620.3750.537L-011L-020M-0152/16/123/1/123/15/124/12/125/31/126/14/126/28/127/26/123/1/123/15/123/29/124/27/120142856014285601428560.02.04.08.00.02.04.08.00.02.04.08.0l5.35.25.25.80.60.40.20.31.521.21.2w1.81.91.930.50.50.20.30.10.10.10.1d0.30.10.40.40.20.10.10.10.8110.62.860.993.956.960.0600.0200.0040.0090.1200.2000.1200.072
Turner00000000000000000000000000000000000000000000000000000000000000000000000000000000
M-012
L-001
L-014
L-004
L-008
L-011
L-017
L-019
M--006
M-009
M-010
L-020
M-005
M-007
M-016
M-002
L-018
M-015
M-003
L-013
Time (weeks)
Wound Size (cm3)
Impact of exsalt SD7 on wound size progression over 8
weeks
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
000
Total Change over 8 weeks
Number of Patients
Impact of exsalt SD7 on wound size over a total 8 week
evaluation period
Culture IndexHeavyManyModerateOccasionalFewPatientjan 25th
201213/02/2012 Right Foot Microbio10 April 2012 left heel
microbioIDM-012L-001L-014L-004L-008L-011L-017L-019M-006M-009M-010L-020M-005M-007M-016M-002L-018M-015M-003L-013Date2/22/123/8/123/22/124/19/121/16/121/30/122/13/123/13/122/27/123/12/123/26/124/27/121/30/122/13/122/28/123/26/122/16/122/29/123/15/124/12/122/16/123/1/123/15/124/12/124/19/125/2/125/16/126/13/125/17/125/29/126/13/127/12/122/13/122/27/123/12/124/10/122/16/123/1/123/15/124/12/122/16/122/29/123/15/124/12/125/31/126/14/126/28/127/26/122/8/122/22/123/8/124/5/122/13/122/27/123/12/124/10/123/23/124/5/125/17/121/25/122/8/122/22/123/21/121/25/122/8/122/22/123/21/123/1/123/15/123/29/124/27/121/25/122/8/122/22/123/21/122/23/123/8/123/22/124/19/12Days01029560142857014286001429560132856014285601327570122756014285701428560132856014285601429570142857013285501428560142856014285601428560142856Weeks0.01.44.18.00.01.44.18.00.02.04.08.60.02.04.18.00.01.94.08.00.02.04.08.00.01.93.98.10.01.73.98.00.02.04.08.10.02.04.08.00.01.94.08.00.02.04.08.00.02.04.18.10.02.04.08.10.01.94.07.90.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.0MicrobioEpithelial
cellsoccationalfewoccationaloccationaloccationalfewoccationaloccationaloccfewoccationalmoderatefewoccationalmoderatefewfewfewoccationalclosedfewfewfewmodoccationaloccationalfewoccationalfewfewLeukocytesoccationaloccationaloccoccationalPuss
cellsfewfewmoderatemoderategram +
coccimanyoccationalfewoccationalfewoccmoderatefewmanyfewoccationalmanyfewmanyfewoccationalmoderateoccationaloccationalfewmanymanyGram
+
bacillifewmanyoccationalmoderatefewfewfewoccationalfewfewoccationalmoderatemanyoccationalmoderatefewfewGram
- cocci1moderateoccationalGram -
baciilli1moderatemanymanymanyheavymoderatemanyfewfewoccationalfewoccationalmanyfewoccationalfewmanyCommensal111heavy11mixedmixed1111111111111MRSAheavyHeavypseudomonasheavyheavyHeavyheavymanymanypredominantlyheavyheavystaphheavyheavymoderateheavyheavymoderateheavyheavyheavyheavyheavyheavye-coliheavyNo
bacteria111111no growth 48 h11group b strep1heavy11mixed gram
(-)heavyheavyheavyheavy1candida (not albicans)
Comments (on week)Patient0248M-012decreased painchem burning-
removed the next day, new med. G. ebopentinincreased pain,
swellingL-001tetracycline, new meds bactrobandoxycilin for
MRSADoxycilinL-014new opening, skin
tearL-004L-008cyprofloxinL-011ABI Tibial R= 1.18 L= 1.13, Toe 0.70,
106 mmHgfolliculitis L. pretibialnew open area, 0.1 x 0.1 pt
skinL-017L-019M-006consultation 23 march with Dr. QueenM-009pain in
rt knee & ankleM-010moxyfloxin for painL-020M-005Dressing
change every other day- 1st visit with Dr. Quin Feb 2 2012 with flu
in 3 weeksSeen by Dr. Queen reg visitseen by Dr. Queen regular
visitwound closedM-007Rt med leel: 1 x 0.9 woundsulfatrin 80/160
mg, metronidezdae 500 mg, 17-2-12 toe infection right footnote to
continue exsalt 3x/week Dr. Queen regular visitsM-016WBC-7.0, neut
4.43, lymph-1.82 ESR 5.0, mono-0.56 EOS 0.21, Platelet 220, Baso
0.07, MPV 10, microcytosis- mild, hypochromasia- mildno staining,
good integrity, decreased draining with exsaltfinished
moxyfloxinOct 12th, 2012- closed with exsalt 202 days later (29 wks
later)M-0022 areas on right leg(pretibial, 1st meteoleus-
trauma)7-2-12 new area on rt 2nd toe 0.6 x 1- Increased pain-
Ciprofloxacinwound on Rt 2nd toe healedL-018ciprofloxindecreased
exudate, decreased odourwound divided into two
islanddsM-015betohistine 20-mar 12 inner cor infection- saw family
doctorM-003Exciton gave ok to go ahead with study-continued with
exsalt till juneL-013continued with exsalt till august
Concentration required to prevent the formation of biofilm
after 4 hous in solutionSilver OxysaltsAgNO3SpeciesuMppmuMppmE.
coli9.71.0519.52.10P. aerug19.52.1039.14.22S.
aureus62.56.743000323.7048Greater thanConcentration required to
dimish planktonic populationsSilver
OxysaltsAgNO3SpeciesuMppmuMppmE. coli9.71.0539.14.22P.
aerug9.71.0519.52.10S. aureus62.56.743000323.70
Chart50248
Cumulaive Scores
Time (weeks)
Cumulative Pain Scores
Pain
40
40
30
29.5
Patient InfoComorbiditiesDMDiabetes MellitusLDLiver
DiseaseObObesitySmSmokingHCHypercholestriaPVDPerpheral Vascular
DiseaseHLHyperlipidemaAngAngioplastyVIVenous
insufficiencyBWBilateral WoundsHTHypertensionTIATransient Ischemic
AttackTDThyroid diseaseSASleep
ApneiaPatientSummaries1234567891011121314151617181920IDAvgStdevMeanRangeM-012L-001L-014L-004L-008L-011L-017L-019M-006M-009M-010L-020M-005M-007M-016M-002L-018M-015M-003L-013Age56.812.955.050.05546524658497574316255674550496376445781sexmale16female4malemalemalefemalemalefemalemalemalemalemalemalefemaleMalefemaleMaleMalemaleMalemalemaleheight6'1"5'4"5'6"6'5"6'5'8"5'7"5'10"wt
(lbs)285335165290200
lbs230189200WoundFootLegLegLegLegLegLegLegFootFootFootLegFootFootFootFootLegFootFootLeglocationleft
4th medialright lateral legright medial ankleright lateral legrt
leg pretibialLeft med. Legleft malleolusleft leg ulcerleft heelrt
1st met heelrt 1st toert leg melleolusfirst metatorsal sheelleft
second met heelleft 5th met heelleft 1st toeleft med leg
malleolusleft 2nd met heelrt 5th met heelrt met malleolusduration
(mo)22.214.824.058.0524362424123624121222424910122448601
causeneruopathyvenous stasisvenous statsis ulcerVSUnecrobiosis
lipoidiciasurgeryVSvsupressure from
braceneuropathyneuropathyvsuNeuropathypressureneuropathydiabetic
neuropathic ulcerVIneuropathyneuropathicVSU2
causediabetesvenoustraumaV-HTdiabetesVSUVHTvs dieasespina
bifidadiabetesdiabetesvenous diseasediabetesneuropathynerve damage
(trauma)diabetesleined five
factorDiabetesdiabeticVHTComorbiditiesDM, O, HC, HL, VI, HTDM, Ob,
VIVI, car accident, broken femur, ABPI 1.08TD, LD, HTDM, HC/HL, Sm,
PVD, VI, HT, Ang, BWVIDM, HC/HL, VI, HT, two wounds on left
melleous Top wound = 1.9 x 1.0 lower wound = study woundHC/HL, VI,
HTspina bifida,DM, VI, TIA, SADM, HC/HL,TD,HTHC/HL, TD, VI, HT- apr
25th Toe 0.76 ABI 109 R leg 1.10,158DM, VI, decreased hearing in
right ear, ABPI = 1.12Ob, TD, malignant ashma, uteral cancer
(4years ago)HC/HL, VI, HT, wound @left toe, 2002 nerve damage, hip
fracture, high urinic acidDM, VI, HT,VI, rt leg med malleolus ulcer
0.2 x 0.2DM, Wound left footDM, HC/HL, VI, Renal failure (on
dialysis over 600 creatinine) Diabetic neruopathy (ABPI L=0.92
R=0.87)HC/HL, TD, HT, wounds on both legs, Rt med/L lat, ABPI
1.23medicationsMetformin, metoprolol, fluosemide 40,20, Asparin 81
mgmetformin, COQ10, Zn-Cu balance, probiotic 90, prion, acticoat
flex, antibioticsDoxycillinTrentolwortin, trentol, docycycline,
crestor, adolot, diovon, vit diolene,
compressionpitropenMetroprolol, tartrate, metformin, vit B12,
amlodipihe, bedulate, asprin, mazaar, diamicron, lamasilamlodipine,
asprin, imolopomine, tisinophihe,lipitor, levothyroxine,
fentofibreteNew offloading shoe Jan 13th,Paxel, nortriptylini,
oxylutynine chloride, paroxtine, obesitymoxifloxin, accupri,
allopurinol, lipitorsolofelk 500 mg, metformin 500 mg, glyberide 5
mg, warfarin 2.5 mg, nifedipine 60 mg, enelopril 5 mgmoxyfloxin,
worfin, flo max, vitaminsciprofloxin, metaformin, glucosoleCalcium
oyster, phosrenol, eurflex, lipitor, recaltrol, entrophen, senoket,
relloaite, epoinect, quinine, tiemolca, rotioectosome, ciprelox,
lorazepam, nitrolinoprol sprayIrbesorten 300 mg, synthroid 0.07 mg,
amlodirinebesylate 5 mg, hydrochlorothiolsrole 25 mg, bentoxifyline
400 mg, crestor 5 mgPrevious dressings usedmefix, telfaActicoat
flex, silvercel, antibioticsActicoat burn, silvercel, acticoat,
iodosorbMesorbbetaine, inadine, telfa, mefix, Jan 24th acticoat
flex5 Dec 2011- Inadine & Mefixdec 12th 2011- betadine,
inadine, ETE, mefixNov 25 2011- inadine, mepore, allevyn/Oct 2011-
inadeine, mepore2 may 2012- inadine, ETE, mesorb
TimelineClinical TimelineIntended (days)Intended
(weeks)01428560248PatientDates (Calendar)Actual (days)Actual
(weeks)M-0122/22/123/8/123/22/124/19/12010295601.44.18.0L-0011/16/121/30/122/13/123/13/12014285702.04.08.1L-0142/27/123/12/123/26/124/27/12014286002.04.08.6L-0041/30/122/13/122/28/123/26/12014295602.04.18.0L-0082/16/122/29/123/15/124/12/12013285601.94.08.0L-0112/16/123/1/123/15/124/12/12014285602.04.08.0L-0174/19/125/2/125/16/126/13/12013275701.93.98.1L-0195/17/125/29/126/13/127/12/12012275601.73.98.0M-0062/13/122/27/123/12/124/10/12014285702.04.08.1M-0092/16/123/1/123/15/124/12/12014285602.04.08.0M-0102/16/122/29/123/15/124/12/12013285601.94.08.0L-0205/31/126/14/126/28/127/26/12014285602.04.08.0M-0052/8/122/22/123/8/124/5/12014295702.04.18.1M-0072/13/122/27/123/12/124/10/12014285702.04.08.1M-0163/23/124/5/125/17/12013285501.94.07.9M-0021/25/122/8/122/22/123/21/12014285602.04.08.0L-0181/25/122/8/122/22/123/21/12014285602.04.08.0M-0153/1/123/15/123/29/124/27/12014285602.04.08.0M-0031/25/122/8/122/22/123/21/12014285602.04.08.0L-0132/23/123/8/123/22/124/19/12014285602.04.08.0Avg0.013.528.156.40.01.94.08.1Stdev0.01.00.51.00.00.10.10.1
PainFootLegPain Description (on week)WeekTotal Change
(w8-w0)SummariesPatient02480248Change (w2-w0)Change (w4-w2)Change
(w8-w4)M-012throbbingthrobbingshootingthrobbing6.010.02.54.5-1.54.0-7.52.0L-001stingneedle1.01.01.01.000.00.00.0L-0140.00.00.00.000.00.00.0L-004tightsting
1h of dressing changepain when
walking5.07.02.58.032.0-4.55.5L-008burnburnburn0.51.00.01.510.5-1.01.5L-011sharp/stabsharp/stabsharpshooting3.02.04.04.01-1.02.00.0L-017stiffness0.00.00.03.53.50.00.03.5L-019burnbruise1.01.51.51.000.50.0-0.5M-0060.00.00.00.000.00.00.0M-0090.00.00.00.000.00.00.0M-010burnburn-
pain to
touchburn0.01.03.01.011.02.0-2.0L-020burnthrobburnprickly2.01.01.01.0-1-1.00.00.0M-005burn,
sharpburnburnclosed5.55.54.00.0-5.50.0-1.5-4.0M-007pressure,
intermitent
sharpsharp10.00.00.02.0-8-10.00.02.0M-0160.00.00.00.000.00.00.0M-002burnnail
through
toenail2.55.05.00.0-2.52.50.0-5.0L-018trobbingstiningintermittent2.51.50.50.0-2.5-1.0-1.0-0.5M-015nusencepressure0.01.01.01.011.00.00.0M-0030.00.00.00.000.00.00.0L-013stingburnburnsting1.02.54.01.001.51.5-3.0n
patients with pain12.013.012.012.00Cumulative Total
Pain40.040.030.029.598129No Change6456Decreased Pain5835Increased
PainFootPain Description (on week)WeekTotal Change
(w8-w0)SummariesPatient02480248Change (w2-w0)Change (w4-w2)Change
(w8-w4)M-012throbbingthrobbingshootingthrobbing6.010.02.54.5-1.54.0-7.52.0M-0060.00.00.00.000.00.00.0M-0090.00.00.00.000.00.00.0M-010burnburn-
pain to touchburn0.01.03.01.011.02.0-2.0M-005burn,
sharpburnburnclosed5.55.54.00.0-5.50.0-1.5-4.0M-007pressure,
intermitent
sharpsharp10.00.00.02.0-8-10.00.02.0M-0160.00.00.00.000.00.00.0M-002burnnail
through
toenail2.55.05.00.0-2.52.50.0-5.0M-015nusencepressure0.01.01.01.011.00.00.0M-0030.00.00.00.000.00.00.0n
patients with pain4.05.05.04.00Cumulative Total
Pain24.022.515.58.50121No Change4123Decreased Pain1412Increased
PainLegPain Description (on week)WeekTotal Change
(w8-w0)SummariesPatient02480248Change (w2-w0)Change (w4-w2)Change
(w8-w4)L-001stingneedle1.01.01.01.000.00.00.0L-0140.00.00.00.000.00.00.0L-004tightsting
1h of dressing changepain when
walking5.07.02.58.032.0-4.55.5L-008burnburnburn0.51.00.01.510.5-1.01.5L-011sharp/stabsharp/stabsharpshooting3.02.04.04.01-1.02.00.0L-017stiffness0.00.00.03.53.50.00.03.5L-019burnbruise1.01.51.51.000.50.0-0.5L-020burnthrobburnprickly2.01.01.01.0-1-1.00.00.0L-018trobbingstiningintermittent2.51.50.50.0-2.5-1.0-1.0-0.5L-013stingburnburnsting1.02.54.01.001.51.5-3.0n
patients with pain8.08.07.08.00Cumulative Total
Pain16.017.514.521.02133No Change2332Decreased Pain4423Increased
Pain
Pain000
Total Change over 8 weeks
Number of Patients
Impact of exsalt SD7 on Pain Scores over a total 8 week
evaluation period
NERDS-STONES0000
Cumulaive Scores
Time (weeks)
Cumulative Pain Scores
Pain
0
0
0
0
BWATFootLegNERDS Infection Signs (on week)Total Change
(w8-w0)NERDS SummariesSTONEES Infection Signs (on week)Total Change
(w8-w0)STONEES Summaries0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0121000-1-1.00.00.010021-1.00.02.0L-0011000-1-1.00.00.010021-1.00.02.0L-014000110.00.01.010010-1.00.01.0L-00421020-1.0-1.02.0010221.0-1.02.0L-0081210-11.0-1.0-1.0131102.0-2.00.0L-011000110.00.01.0011221.00.01.0L-017000110.00.01.01010-1-1.01.0-1.0L-019001220.01.01.01010-1-1.01.0-1.0M-006000000.00.00.02111-1-1.00.00.0M-009010001.0-1.00.0020112.0-2.01.0M-010000000.00.00.01000-1-1.00.00.0L-020000000.00.00.01100-10.0-1.00.0M-005010001.0-1.00.0010001.0-1.00.0M-007001000.01.0-1.0001110.01.00.0M-016000000.00.00.0111100.00.00.0M-0021000-1-1.00.00.0001000.01.0-1.0L-0181110-10.00.0-1.010210-1.02.0-1.0M-015000000.00.00.0110100.0-1.01.0M-003000000.00.00.0010001.0-1.00.0L-01310110-1.01.00.0110100.0-1.01.0n
patients with signs755613119130n patients with signsCumulative
Signs865814141017Cumulative Signs111213129678No Change55435884Signs
Decreased43356658Signs IncreasedFootNERDS Infection Signs (on
week)Total Change (w8-w0)NERDS SummariesSTONEES Infection Signs (on
week)Total Change (w8-w0)STONEES Summaries0248Change (w2-w0)Change
(w4-w2)Change (w8-w4)0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0121000-1-1.00.00.010021-1.00.02.0M-006000000.00.00.02111-1-1.00.00.0M-009010001.0-1.00.0020112.0-2.01.0M-010000000.00.00.01000-1-1.00.00.0M-005010001.0-1.00.0010001.0-1.00.0M-007001000.01.0-1.0001110.01.00.0M-016000000.00.00.0111100.00.00.0M-0021000-1-1.00.00.0001000.01.0-1.0M-015000000.00.00.0110100.0-1.01.0M-003000000.00.00.0010001.0-1.00.0n
patients with signs755656460n patients with signsCumulative
Signs22106747Cumulative Signs0000No Change2278No Change2221Signs
Decreased2384Signs Decreased0110Signs Increased3358Signs
IncreasedNERDS Infection Signs (on week)Total Change (w8-w0)NERDS
SummariesSTONEES Infection Signs (on week)Total Change
(w8-w0)STONEES Summaries0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)0248Change (w2-w0)Change (w4-w2)Change
(w8-w4)PatientL-0011000-1-1.00.00.010021-1.00.02.0L-014000110.00.01.010010-1.00.01.0L-00421020-1.0-1.02.0010221.0-1.02.0L-0081210-11.0-1.0-1.0131102.0-2.00.0L-011000110.00.01.0011221.00.01.0L-017000110.00.01.01010-1-1.01.0-1.0L-019001220.01.01.01010-1-1.01.0-1.0L-020000000.00.00.01100-10.0-1.00.0L-0181110-10.00.0-1.010210-1.02.0-1.0L-01310110-1.01.00.0110100.0-1.01.0n
patients with signs755613119130n patients with signsCumulative
Signs644814141017Cumulative Signs111213129678No Change55435884Signs
Decreased43356658Signs
IncreasedPatientIDM-012L-001L-014L-004L-008L-011L-017L-019M-006M-009M-010L-020M-005M-007M-016M-002L-018M-015M-003L-013Weeks0.01.44.18.00.02.04.08.10.02.04.08.60.02.04.18.00.01.94.08.00.02.04.08.00.01.93.98.10.01.73.98.00.02.04.08.10.02.04.08.00.01.94.08.00.02.04.08.00.02.04.18.10.02.04.08.10.01.94.07.90.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.0Nnon-healing111111E
exudate11Rred/bleeding111111Ddebris1111111111111SsmellTotal
NERDS10001000000121021210000100010012000001000000000001000010000010001110000000001011S
size1111111T temp1111111111111111111111111111111Oos, probeNnew
breakdown111Eexudate,1Eerhythema/edema1111111111111SsmellTotal
STONEES10021002100101021311011210101010211102011000110001000011111100101021110101001101
BWAT000000
NERDS
STONEES
Number of Patients
Impact of exsalt SD7 on NERDS & STONEES clinical signs and
symptoms over a total 8 week evaluation period
SizeFootLegBWAT (on week)Summaries0248Total ChangeChange
(w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0122733286.0-5.0L-00130343127-34.0-3.0-4.0L-014332632-7.06.0L-0043536314051.0-5.09.0L-00836393833-33.0-1.0-5.0L-01139323130-9-7.0-1.0-1.0L-017383436-4.02.0L-01936263632-4-10.010.0-4.0M-00621272620-16.0-1.0-6.0M-0092734213147.0-13.010.0M-01034283232-2-6.04.00.0L-02030292726-4-1.0-2.0-1.0M-00528292913-151.00.0-16.0M-00734282724-10-6.0-1.0-3.0M-01634282724-10-6.0-1.0-3.0M-002322828331-4.00.05.0L-01835302326-9-5.0-7.03.0M-015292726312-2.0-1.05.0M-00334262627-7-8.00.01.0L-01339364033-6-3.04.0-7.0AVG32.5530.529.7528.35294117650031No
Change1313128BWAT Decreased4756BWAT IncreasedFootBWAT (on
week)Summaries0248Total ChangeChange (w2-w0)Change (w4-w2)Change
(w8-w4)PatientM-0122733286.0-5.0M-00621272620-16.0-1.0-6.0M-0092734213147.0-13.010.0M-01034283232-2-6.04.00.0M-00528292913-151.00.0-16.0M-00734282724-10-6.0-1.0-3.0M-01634282724-10-6.0-1.0-3.0M-002322828331-4.00.05.0M-015292726312-2.0-1.05.0M-00334262627-7-8.00.01.03002882702350031No
Change1313128BWAT Decreased4756BWAT IncreasedLegBWAT (on
week)Summaries0248Total ChangeChange (w2-w0)Change (w4-w2)Change
(w8-w4)PatientL-00130343127-34.0-3.0-4.0L-014332632-7.06.0L-0043536314051.0-5.09.0L-00836393833-33.0-1.0-5.0L-01139323130-9-7.0-1.0-1.0L-017383436-4.02.0L-01936263632-4-10.010.0-4.0L-02030292726-4-1.0-2.0-1.0L-01835302326-9-5.0-7.03.0L-01339364033-6-3.04.0-7.03513223252470031No
Change1313128BWAT Decreased4756BWAT
IncreasedPatientIDM-012L-001L-014L-004L-008L-011L-017L-019M-006M-009M-010L-020M-005M-007M-016M-002L-018M-015M-003L-013Weeks0.01.44.18.00.01.44.18.00.02.04.08.60.02.04.18.00.01.94.08.00.02.04.08.00.01.93.98.10.01.73.98.00.02.04.08.10.02.04.08.00.01.94.08.00.02.04.08.00.02.04.18.10.02.04.08.10.01.94.07.90.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.00.02.04.08.0BWAT1-
size11111111122244342222212222221111111111111111111111111111111111132221111111122222-
depth33332333313333333343333333333333333233333333333233333333333333333333333333333337-
exuda
