Combatting wound biofilm and recalcitrance with a novel anti-biofilm Hydrofiber® wound dressing

AbstractBackgroundBiofilm is an impediment to wound healing as a consequence of its proven ability to impair epithelialization, granulation tissue formation and normal inflammatory processes, as well as protecting wound pathogens from antibiotics and antiseptics. With this in mind, a project was initiated to develop a combined anti-biofilm/antimicrobial technology that could be incorporated into a wound dressing to maximize effectiveness against wound pathogens existing in their predominant biofilm form.MethodsInitially, a wide range of anti-biofilm agents in combination with ionic silver were screened in a rapid throughput in vitro biofilm model. Selected agents were incorporated into a new wound dressing format and subsequently tested in vitro against antibiotic-resistant pathogens in their most tolerant biofilm form.ResultsThe combination of ionic silver with a metal chelating agent and a surfactant was shown to produce a synergistic effect (referred to as Ag+ Technology) that substantially improved the antimicrobial efficacy of ionic silver against biofilm pathogens in a simulated wound biofilm model.ConclusionBy combining anti-biofilm and antimicrobial components that work in synergy to disrupt biofilm and expose associated wound pathogens to the antimicrobial action of ionic silver, it is anticipated that this new technology incorporated into an advanced Hydrofiber® wound dressing will contribute significantly to managing biofilm infections and encouraging healing in patients debilitated by recalcitrant wounds

DEVELOPMENT OF A NEXT-GENERATION ANTIMICROBIAL WOUND DRESSING

Odgođeno cijeljenje rana zbog infekcije je teret zdravstvenim sustavima, a jednako tako i pacijentu i onome koji skrbi za njega. Bitan čimbenik u nastajanju infekcije i odgođenog cijeljenja je razvoj i prisutnost biofi lma u ranama. Biofi lm je zajednica mikroorganizama, zaštićena izvanstaničnim sluzavim matriksom u rani, koji može tolerirati obranu domaćina i primijenjena antimikrobna sredstva, kao što su antibiotici ili antimikrobne obloge. Rastući broj znanstvenih dokaza upućuje da biofilm već egzistira u većini kroničnih rana, a može biti i prethodnik infekciji dok istodobno uzrokuje odgođeno cijeljenje. In vivo modeli pokazali su da su upala, granulacija i epitelizacija, te procesi normalnog cijeljenja rane narušeni prisustvom biofilma. Izazov u razvoju nove antimikrobne obloge za ranu bio je da standardna antimikrobna sredstva učinimo učinkovitija protiv biofilma, a rješenje je uslijedilo nakon opsežnih istraživanja i ispitivanja biofi lma. Kombinacija metalnog kelatora, površinski aktivne tvari i kontrole pH faktora pokazala je snažnu sinergističku anti-biofi lm akciju u oblozi od karboksimetilceluloze sa 1,2 % ionskog srebra. Ta je učinkovitost testirana i dokazana u kompleksnim in vitro i in vivo modelima rana s biofilmom, a zatim i u klinički kontroliranim studijama, i to u studiji na 42-pacijenta i 113 kliničkih evaluacija. Naknadno ispitivanje nastavljeno je nakon dostupnosti obloge u evaluaciji na 112 slučaja, gdje je obloga pokazala učinkovito kontroliranje eksudata i suspektnog biofi lma na ranama koje teško cijele i pri tome poticanje procesa cijeljenja rana i to nakon prosječno 4 tjedna primjene nove obloge u inače standardnom protokolu njege. To je bilo popraćeno niskim brojem nuspojava. U drugoj procjeni bili su evaluirani i klinički znakovi infekcije i podatci o veličini rane, prije i nakon procjene. Nakon prosječno 5,4 tjedana uporabe obloge, svi su klinički znakovi infekcije bili reducirani, s prosječnom učestalošću od 36 % do 21 %. U prosjeku u 62 % rana postignuta je redukcija veličine, uz smanjenje veličine do 90 % i 10 potpuno zacijeljenih rana. Najnoviji kliničkih dokazi za novu generaciju antimikrobne obloge za ranu potvrđuju njenu sigurnost i učinkovitost u kontroli eksudata, infekcije i biofi lma, a osim toga potvrđuju i zacijeljivanje rana koje dugo i teško ili uopće ne cijele. Znanstvenu potporu za najnoviju tehnologiju i generaciju antimikrobne obloge potvrđuju in vitro i in vivo dokazi, tako da su buduća komparativna i randomizirana klinička ispitivanja neophodna za potpuno razumijevanje kliničke i ekonomske učinkovitosti koju može donijeti ova najnovija tehnologija.Delayed wound healing due to infection is a burden on healthcare systems, and the patient and caregiver alike. An emerging factor in infection and delayed healing is the presence development of biofilm in wounds. Biofilm is communities of microorganisms, protected by an extracellular matrix of slime in the wound, which can tolerate host defences and applied antimicrobials such as antibiotics or antimicrobial dressings. A growing evidence base exists suggesting that biofi lm exists in a majority of chronic wounds, and can be a precursor to infection while causing delayed healing itself. In vivo models have demonstrated that the inflammatory, granulation and epithelialization processes of normal wound healing are impaired by biofi lm presence. The challenge in the development of a new antimicrobial wound dressing was to make standard antimicrobial agents more effective against biofilm, and this was answered following extensive biofilm research and testing. A combination of metal chelator, surfactant and pH control displayed highly synergistic anti-biofi lm action with 1.2% ionic silver in a carboxymethylcellulose dressing. Its effectiveness was challenged and proven in complex in vitro and in vivo wound biofi lm models, followed by clinical safety and performance demonstrations in a 42-patient study and 113 clinical evaluations. Post-market surveillance was conducted on the commercially available dressing, and in a 112-case evaluation, the dressing was shown to effectively manage exudate and suspected biofi lm while shifting diffi cultto-heal wounds onto healing trajectories, after an average of 4 weeks of new dressing use in otherwise standard wound care protocols. This was accompanied by a low frequency of dressing related adverse events. In a second evaluation, clinical signs of infection and wound dimension data, before and after the evaluations, were also available. Following an average of 5.4 weeks of dressing use, all signs of clinical infection were reduced, from an average frequency of 36% to 21%. An average of 62% wound size reduction was achieved, with 90% of wounds reducing in size and 10 wounds healing completely. The new clinical evidence for this next-generation antimicrobial wound dressing suggests it is safe and effective at managing exudate, infection and biofilm, while it can shift established, stubborn wounds onto healing trajectories. The scientific rationale for this new dressing technology is supported by in vitro and in vivo evidence, so now further comparative, randomized and outcome-based clinical studies are required to fully understand the clinical and economic benefits this new dressing technology can bring

Wound Biofilm and Therapeutic Strategies

Since the turn of the millennium, an evolving body of scientific and clinical evidence indicates that biofilm is implicitly linked to delayed wound healing and infection. Currently, wound anti-biofilm strategies rely on non-specific wound bed preparation techniques involving physical debridement and cleansing, and innovative technologies designed to specifically manage biofilm have only just begun to emerge. The first output of anti-biofilm research and product development in wound care show great promise for patients, clinicians and healthcare institutions. The aim of this chapter is to address the current clinical biofilm problem, describe existing and emerging strategies to combat wound biofilm and review the available evidence

Do You K now D.O.?: Pre Medical Students’ Knowledge of Osteopathic Medicine and Its Relation to Burnout

It is estimated that in the near future there will be a shortage of physicians available to keep up with the needs of a growing older population. To try to account for this, medical schools are expanding class sizes and new schools are being created. While both allopathic and osteopathic schools are expanding, osteopathic schools are doing so a much faster rate. Unfortunately, it seems many students enter their undergraduate careers unaware of osteopathic medicine despite having an interest in medical school. Undergraduate student interest in becoming a medical doctor continues to rise, but so too does the difficulty of earning acceptance to medical school. In this competitive environment, little is known about students’ knowledge of their medical school options. Moreover, as undergraduate students’ emotional health continues to decline, little is known about whether premedical students experience or are at increased risk for the burnout symptoms reported by medical students and other physicians in training. This study examined students’ knowledge of osteopathic medicine, how they learned of osteopathic medicine, and any reported burnout

The TRENDS High-Contrast Imaging Survey. VII. Discovery of a Nearby Sirius-like White Dwarf System (HD 169889)

Monitoring the long-term radial velocity (RV) and acceleration of nearby stars has proven an effective method for directly detecting binary and substellar companions. Some fraction of nearby RV trend systems are expected to be comprised of compact objects that likewise induce a systemic Doppler signal. In this paper, we report the discovery of a white dwarf companion found to orbit the nearby ($\pi = 28.297 \pm 0.066$ mas) G9 V star HD 169889. High-contrast imaging observations using NIRC2 at Keck and LMIRCam at the LBT uncover the ($\Delta H = 9.76 \pm 0.16$, $\Delta L' = 9.60 \pm 0.03$) companion at an angular separation of 0.8'' (28 au). Thirteen years of precise Doppler observations reveal a steep linear acceleration in RV time series and place a dynamical constraint on the companion mass of $M \geq 0.369 \pm 0.010 M_{\odot}$. This "Sirius-like" system adds to the census of white dwarf companions suspected to be missing in the solar neighborhood.Comment: Accepted to Ap

WISEP J180026.60+013453.1: A Nearby Late L Dwarf Near the Galactic Plane

We report a nearby L7.5 dwarf discovered using the Preliminary Data Release of the Wide-field Infrared Survey Explorer (WISE) and the Two Micron All-Sky Survey (2MASS). WISEP J180026.60+013453.1 has a motion of 0.42 arcsec/yr and an estimated distance of 8.8 \pm 1.0 pc. With this distance, it currently ranks as the sixth closest known L dwarf, although a trigonometric parallax is needed to confirm this distance. It was previously overlooked because it lies near the Galactic Plane (b=12). As a relatively bright and nearby late L dwarf with normal near-infrared colors, W1800+0134 will serve as a benchmark for studies of cloud-related phenomena in cool substellar atmospheres.Comment: 12 pages, 2 figure, accepted to the Astronomical Journal (AJ

Legislator dissent as a valence signal

Existing research suggests that voters tend to respond positively to legislator independence due to two types of mechanism. First, dissent has an indirect effect, increasing a legislator’s media coverage and personal recognition among constituents (profile effects). Second, constituents react positively to dissent when this signals that the legislator has matching political or representational preferences (conditional evaluation). We argue for a third effect: dissent acts as a valence signal of integrity and trustworthiness. Consistent with the valence signalling mechanism, we use new observational and experimental evidence to show that British voters have a strong and largely unconditional preference for legislators who dissent. Our findings pose a dilemma for political systems which rely on strong and cohesive parties

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood