Topically Applied Therapies for the Treatment of Skin Disease: Past, Present, and Future.

The purpose of this review is to summarize essential biological, pharmaceutical, and clinical aspects in the field of topically applied medicines that may help scientists when trying to develop new topical medicines. After a brief history of topical drug delivery, a review of the structure and function of the skin and routes of drug absorption and their limitations is provided. The most prevalent diseases and current topical treatment approaches are then detailed, the organization of which reflects the key disease categories of autoimmune and inflammatory diseases, microbial infections, skin cancers, and genetic skin diseases. The complexity of topical product development through to large-scale manufacturing along with recommended risk mitigation approaches are then highlighted. As such topical treatments are applied externally, patient preferences along with the challenges they invoke are then described, and finally the future of this field of drug delivery is discussed, with an emphasis on areas that are more likely to yield significant improvements over the topical medicines in current use or would expand the range of medicines and diseases treatable by this route of administration. SIGNIFICANCE STATEMENT: This review of the key aspects of the skin and its associated diseases and current treatments along with the intricacies of topical formulation development should be helpful in making judicious decisions about the development of new or improved topical medicines. These aspects include the choices of the active ingredients, formulations, the target patient population's preferences, limitations, and the future with regard to new skin diseases and topical medicine approaches.

Efficacy of Different Hair and Skin Decontamination Strategies with Identification of Associated Hazards to First Responders.

Background: Established procedures for mass casualty decontamination involve the deployment of equipment for showering with water (such as the ladder pipe system [LPS] and technical decontamination [TD]). This necessarily introduces a short, but critical delay. The incorporation of dry decontamination to the incident response process offers the potential to establish a more rapid and timely intervention. Objectives: To investigate the effectiveness of various dry (DD) and wet decontamination strategies for removing a chemical warfare simulant (methyl salicylate; MS) from the hair and skin of human volunteers. Methods: The simulant was applied to volunteers via whole body exposure to an aerosol. Three decontamination protocols (dry, LPS and technical decontamination) were applied, singly and in various combinations. The efficacy of the protocols was evaluated by fluorescent photography and analysis of residual MS from skin/hair swabs, decontamination materials and air samples. Results: Dry decontamination was effective, with the greatest reduction in skin and hair contamination arising from the "Triple Protocol" (DD+LPS+TD). Secondary hazards associated with contaminated individuals and equipment decreased as the number of decontamination procedures increased. In particular, dry decontamination reduced the potential contact and inhalation hazard arising from used washcloths, towels and vapor within the TD units. Discussion: The introduction of dry decontamination prior to wet forms of decontamination offers a simple strategy to initiate treatment at a much earlier opportunity, with a corresponding improvement in clinical outcomes and substantial reduction of secondary hazards associated with operational processes.

Evaluation of US Federal Guidelines (Primary Response Incident Scene Management [PRISM]) for Mass Decontamination of Casualties During the Initial Operational Response to a Chemical Incident.

STUDY OBJECTIVE: The aim of this study was to evaluate the clinical and operational effectiveness of US federal government guidance (Primary Response Incident Scene Management [PRISM]) for the initial response phase to chemical incidents. METHODS: The study was performed as a large-scale exercise (Operation DOWNPOUR). Volunteers were dosed with a chemical warfare agent simulant to quantify the efficacy of different iterations of dry, ladder pipe system, or technical decontamination. RESULTS: The most effective process was a triple combination of dry, ladder pipe system, and technical decontamination, which attained an average decontamination efficiency of approximately 100% on exposed hair and skin sites. Both wet decontamination processes (ladder pipe system and technical decontamination, alone or in combination with dry decontamination) were also effective (decontamination efficiency >96%). In compliant individuals, dry decontamination was effective (decontamination efficiency approximately 99%), but noncompliance (tentatively attributed to suboptimal communication) resulted in significantly reduced efficacy (decontamination efficiency approximately 70%). At-risk volunteers (because of chronic illness, disability, or language barrier) were 3 to 8 times slower than ambulatory casualties in undergoing dry and ladder pipe system decontamination, a consequence of which may be a reduction in the overall rate at which casualties can be processed. CONCLUSION: The PRISM incident response protocols are fit for purpose for ambulatory casualties. However, a more effective communication strategy is required for first responders (particularly when guiding dry decontamination). There is a clear need to develop more appropriate decontamination procedures for at-risk casualties.

Optimization of Nonambulant Mass Casualty Decontamination Protocols as Part of an Initial or Specialist Operational Response to Chemical Incidents.

Objective: The UK's Initial Operational Response (IOR) is a new process for improving the survival of multiple casualties following a chemical, biological, radiological or nuclear incident. Whilst the introduction of IOR represents a patient-focused response for ambulant casualties, there is currently no provision for disrobe and dry decontamination of nonambulant casualties. Moreover, the current specialist operational response (SOR) protocol for nonambulant casualty decontamination (also referred to as "clinical decontamination") has not been subject to rigorous evaluation or development. Therefore, the aim of this study was to confirm the effectiveness of putatively optimized dry (IOR) and wet (SOR) protocols for nonambulant decontamination in human volunteers. Methods: Dry and wet decontamination protocols were objectively evaluated using human volunteers. Decontamination effectiveness was quantified by liquid chromatography-mass spectrometry analysis of the recovery of a chemical warfare agent simulant (methylsalicylate) from skin and hair of volunteers, with whole-body fluorescence imaging to quantify the skin distribution of residual simulant. Results: Both the dry and wet decontamination processes were rapid (3 and 4 min, respectively) and were effective in removing simulant from the hair and skin of volunteers, with no observable adverse effects related to skin surface spreading of contaminant. Conclusions: Further studies are required to assess the combined effectiveness of dry and wet decontamination under more realistic conditions and to develop appropriate operational procedures that ensure the safety of first responders.

UK's initial operational response and specialist operational response to CBRN and HazMat incidents: a primer on decontamination protocols for healthcare professionals.

The UK is currently in the process of implementing a modified response to chemical, biological, radiological and nuclear and hazardous material incidents that combines an initial operational response with a revision of the existing specialist operational response for ambulant casualties. The process is based on scientific evidence and focuses on the needs of casualties rather than the availability of specialist resources such as personal protective equipment, detection and monitoring instruments and bespoke showering (mass casualty decontamination) facilities. Two main features of the revised process are: (1) the introduction of an emergency disrobe and dry decontamination step prior to the arrival of specialist resources and (2) a revised protocol for mass casualty (wet) decontamination that has the potential to double the throughput of casualties and improve the removal of contaminants from the skin surface. Optimised methods for performing dry and wet decontamination are presented that may be of relevance to hospitals, as well as first responders at the scene of a chemical incident.

Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications.

BACKGROUND: "Residual skin surface components" (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of "normal" RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. METHODS: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography-atmospheric pressure chemical ionisation-mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. RESULTS: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. CONCLUSIONS: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.

The percutaneous toxicokinetics of VX in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant.

This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for the decontamination of superficial, nerve agent-contaminated wounds. Anaesthetized animals were randomly assigned to either control (n = 7), no decontamination (n = 12) or WoundStat™ (n = 12) treatment groups. Pigs were exposed to a 5× LD50 dose of neat, radiolabelled S-[2-(diisopropylamino)ethyl]-O-ethyl methyl-phosphonothioate (VX; or equivalent volume of sterile saline for the control group) via an area of superficially damaged skin on the ear. WoundStat™ was applied at 30 seconds post-exposure to assigned animals. The VX contaminant (or saline) and decontaminant remained in place for the duration of the study (up to 6 hours). Physiological parameters and signs of intoxication were recorded during the exposure period. Skin and organ samples were taken post mortem for 14 C-VX distribution analyses. Blood samples were taken periodically for toxicokinetic and whole-blood acetylcholinesterase (AChE) activity analyses. VX exposure was accompanied by a rapid decrease in AChE activity in all animals, regardless of decontamination. However, decontamination significantly improved survival rate and time and reduced the severity of signs of intoxication. In addition, the distribution of 14 C-VX in key internal organs and post mortem blood samples was significantly lower in the WoundStat™ treatment group. This study demonstrates that WoundStat™ may be a suitable medical countermeasure for increasing both survival rate and time following VX exposure. The results also suggest that AChE activity is not a useful prognostic indicator.

The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant.

PURPOSE: The aim of this study was to evaluate a candidate haemostat (WoundStat™), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model. MATERIALS AND METHODS: An area of approximately 3 cm2 was dermatomed from the dorsal ear skin to a nominal depth of 100 µm. A discrete droplet of 14C-GD (300 µg kg-1) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2 g application of WoundStat™ 30 s after GD challenge. The decontamination efficacy of WoundStat™ against GD was measured by the direct quantification of the distribution of 14C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements. RESULTS: WoundStat™ sequestered approximately 70% of the applied 14C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15 min post WoundStat™ treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat™ treated animals survived the study duration. CONCLUSIONS: The current study has shown that the use of WoundStat™ as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat™ in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.

Hair analysis for the detection of drug use-is there potential for evasion?

BACKGROUND: Hair analysis for illicit substances is widely used to detect chronic drug consumption or abstention from drugs. Testees are increasingly seeking ways to avoid detection by using a variety of untested adulterant products (e.g., shampoos, cleansers) widely sold online. This study aims to investigate adulteration of hair samples and to assess effectiveness of such methods. METHODS: The literature on hair test evasion was searched for on PubMed or MEDLINE, Psycinfo, and Google Scholar. Given the sparse nature of peer-reviewed data on this subject, results were integrated with a qualitative assessment of online sources, including user-orientated information or commercial websites, drug fora and "chat rooms". Over four million web sources were identified in a Google search by using "beat hair drug test" and the first 86 were monitored on regular basis and considered for further analysis. RESULTS: Attempts to influence hair test results are widespread. Various "shampoos," and "cleansers" among other products, were found for sale, which claim to remove analytes. Often advertised with aggressive marketing strategies, which include discounts, testimonials, and unsupported claims of efficacy. However, these products may pose serious health hazards and are also potentially toxic. In addition, many anecdotal reports suggest that Novel Psychoactive Substances are also consumed as an evasion technique, as these are not easily detectable via standard drug test. Recent changes on Novel Psychoactive Substances legislations such as New Psychoactive Bill in the UK might further challenge the testing process. CONCLUSION: Further research is needed by way of chemical analysis and trial of the adulterant products sold online and their effects as well as the development of more sophisticated hair testing techniques.

Captagon: use and trade in the Middle East.

BACKGROUND: Fenetheylline, a psychostimulant drug, often branded as Captagon, is a combination of amphetamine and theophylline. Since the cessation of its legal production in 1986, counterfeited products have been produced illicitly in south-east Europe and far-east Asia. Its profitable trade has been linked to terrorist organizations, including Islamic State of Iraq and the Levant. This study aims to reach up-to-date data, concerning the Captagon e-commerce and use in the Middle East. METHODS: A multi-staged and multi-lingual literature search was carried out. A list of prespecified keywords was applied across medical and paramedical databases, web and Dark web, search engines, social communication media, electronic commerce websites, media networks, and the Global Public Health Intelligence Network database. RESULTS: The use of Captagon as a stimulant in terrorist settings has been marginally covered in the literature. Data can widely be retrieved from Google and AOL search engines, YouTube, and Amazon e-commerce websites, and to a lesser extent from Alibaba and eBay. On the contrary, Middle Eastern e-commerce websites yielded almost no results. Interestingly, the Dark web generated original data for Captagon e-commerce in the Middle East. CONCLUSION: Further investigations are needed on the role that psychoactive drugs play in terrorist attacks and civil war zones. Unless a comprehensive methodological strategy, inclusive of unconventional methods of research, is implemented, it will not be feasible to face such a threat to humanity.

The percutaneous toxicokinetics of Sulphur mustard in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant.

This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for decontamination of superficial (non-haemorrhaging), sulphur mustard-contaminated wounds. The dorsal skin of 12 female pigs was subjected to controlled physical damage and exposed to 10 µL 14 C-radiolabelled sulphur mustard (14 C-SM). Animals were randomly assigned to either a control or a treatment group. In the latter, WoundStat™ was applied 30 s post exposure and left in situ for 1 h. Skin lesion progression and decontaminant efficacy were quantified over 6 h using a range of biophysical measurements. Skin, blood and organ samples were taken post mortem for histopathological assessment, 14 C-SM distribution and toxicokinetic analyses. Application of SM to damaged skin without decontamination was rapidly followed by advanced signs of toxicity, including ulceration and decreased blood flow at the exposure site in all animals. WoundStat™ prevented ulceration and improved blood flow at the exposure site in all decontaminated animals (n = 6). Furthermore, significantly smaller quantities of 14 C-SM were detected in the blood (45% reduction), and recovered from skin (70% reduction) and skin surface swabs (99% reduction) at 6 h post-challenge. Overall, the distribution of 14 C-SM in the internal organs was similar for both groups, with the greatest concentration in the kidneys, followed by the liver and small intestine. WoundStat™ significantly reduced the amount of 14 C-SM recovered from the liver, a key organ for SM metabolism and detoxification. This study demonstrates that WoundStat™ is a suitable product for reducing the ingress and toxicity of a chemical warfare agent. Copyright © 2017 John Wiley & Sons, Ltd.

Development of haemostatic decontaminants for treatment of wounds contaminated with chemical warfare agents. 3: Evaluation of in vitro topical decontamination efficacy using damaged skin.

Previous studies have demonstrated that haemostatic products with an absorptive mechanism of action retain their clotting efficiency in the presence of toxic materials and are effective in decontaminating chemical warfare (CW) agents when applied to normal, intact skin. The purpose of this in vitro study was to assess three candidate haemostatic products for effectiveness in the decontamination of superficially damaged porcine skin exposed to the radiolabelled CW agents, soman (GD), VX and sulphur mustard (HD). Controlled physical damage (removal of the upper 100 µm skin layer) resulted in a significant enhancement of the dermal absorption of all three CW agents. Of the haemostatic products assessed, WoundStat™ was consistently the most effective, being equivalent in performance to a standard military decontaminant (fuller's earth). These data suggest that judicious application of haemostatic products to wounds contaminated with CW agents may be a viable option for the clinical management of casualties presenting with contaminated, haemorrhaging injuries. Further studies using a relevant animal model are required to confirm the potential clinical efficacy of WoundStat™ for treating wounds contaminated with CW agents. Copyright © 2017 John Wiley & Sons, Ltd.

Evaluation of a new topical skin protectant (RD1433) for the prevention and treatment of incontinence-associated dermatitis.

Context Incontinence-associated dermatitis (IAD) is a type of moisture-associated dermatitis caused by repeated skin exposure to urine or stool. A product that could mitigate such symptoms would have a significant impact on cost of care and patients' quality of life. Objective This study compared the clinical efficacy of RD1433 and a comparator product (Vaseline®) in preventing and treating experimental IAD skin lesions. Materials and methods For the "prevention" part of the study, skin sites in eight human volunteers were treated daily for 5 d with either RD1433 or Vaseline® immediately prior to synthetic urine exposure. In the "treatment" part, exposure to synthetic urine was substituted for Vaseline® or RD1433 application on the first 2 d to promote the development of skin lesions prior to the application of the products from day three. Product efficacy was quantified by visual scoring and an array of biophysical instruments. Results Both RD1433 and Vaseline® significantly reduced lesion progression when applied as a prophylactic. When applied as a treatment (following establishment of skin lesions), RD1433 demonstrated a statistically significant improvement in several measures of skin function whereas there was no statistically significant improvement following treatment with Vaseline®. Conclusions The findings of this study suggest that RD1433 may be superior to Vaseline® in the prevention and treatment of experimental IAD lesions. Clearly, further work is required to establish the efficacy of RD1433 with patients in a clinical environment.

Preliminary evaluation of military, commercial and novel skin decontamination products against a chemical warfare agent simulant (methyl salicylate).

Rapid decontamination is vital to alleviate adverse health effects following dermal exposure to hazardous materials. There is an abundance of materials and products which can be utilised to remove hazardous materials from the skin. In this study, a total of 15 products were evaluated, 10 of which were commercial or military products and five were novel (molecular imprinted) polymers. The efficacies of these products were evaluated against a 10 µl droplet of (14)C-methyl salicylate applied to the surface of porcine skin mounted on static diffusion cells. The current UK military decontaminant (Fuller's earth) performed well, retaining 83% of the dose over 24 h and served as a benchmark to compare with the other test products. The five most effective test products were Fuller's earth (the current UK military decontaminant), Fast-Act® and three novel polymers [based on itaconic acid, 2-trifluoromethylacrylic acid and N,N-methylenebis(acrylamide)]. Five products (medical moist-free wipes, 5% FloraFree™ solution, normal baby wipes, baby wipes for sensitive skin and Diphotérine™) enhanced the dermal absorption of (14)C-methyl salicylate. Further work is required to establish the performance of the most effective products identified in this study against chemical warfare agents.

Development of haemostatic decontaminants for the treatment of wounds contaminated with chemical warfare agents. 1: evaluation of in vitro clotting efficacy in the presence of certain contaminants.

The treatment of penetrating, haemorrhaging injuries sustained within a hazardous environment may be complicated by contamination with toxic chemicals. There are currently no specific medical countermeasures for such injuries. Haemostats with an absorbent mechanism of action have the potential to simultaneously stop bleeding and decontaminate wounds. However, a primary requirement of a 'haemostatic decontaminant' is the retention of clotting function in the presence of chemical contaminants. Thus, the aim of this study was to investigate the haemostatic efficacy of seven commercially available haemostats in the presence of toxic chemicals (soman, VX, sulphur mustard, petrol, aviation fuel and motor oil). Clot viscosity was assessed ex vivo using thrombelastography following treatment of pig blood with: (i) toxic chemical; (ii) haemostat; or (iii) haemostat in combination with toxic chemical. Several contaminants (VX, petrol and GD) were found to be pro-haemostatic and none had an adverse effect on the rate with which the test products attained haemostasis. However, the total clot strength for blood treated with certain haemostats in the presence of sulphur mustard, soman and petrol was significantly decreased. Three test products failed to demonstrate haemostatic function in this ex vivo (thrombelastography) model; this was tentatively ascribed to the products achieving haemostasis through a tamponade mechanism of action, which can only be replicated using in vivo models. Overall, this study has identified a number of commercial products that may have potential as haemostatic decontaminants and warrant further investigation to establish their decontaminant efficacy.

Development of haemostatic decontaminants for the treatment of wounds contaminated with chemical warfare agents. 2: evaluation of in vitro topical decontamination efficacy using undamaged skin.

The risk of penetrating, traumatic injury occurring in a chemically contaminated environment cannot be discounted. Should a traumatic injury be contaminated with a chemical warfare (CW) agent, it is likely that standard haemostatic treatment options would be complicated by the need to decontaminate the wound milieu. Thus, there is a need to develop haemostatic products that can simultaneously arrest haemorrhage and decontaminate CW agents. The purpose of this study was to evaluate a number of candidate haemostats for efficacy as skin decontaminants against three CW agents (soman, VX and sulphur mustard) using an in vitro diffusion cell containing undamaged pig skin. One haemostatic product (WoundStat™) was shown to be as effective as the standard military decontaminants Fuller's earth and M291 for the decontamination of all three CW agents. The most effective haemostatic agents were powder-based and use fluid absorption as a mechanism of action to sequester CW agent (akin to the decontaminant Fuller's earth). The envisaged use of haemostatic decontaminants would be to decontaminate from within wounds and from damaged skin. Therefore, WoundStat™ should be subject to further evaluation using an in vitro model of damaged skin.

Optimisation of a dosing regime for a topical skin protectant (barrier cream).

CONTEXT: Topical skin protectants (barrier creams) have the potential to reduce or enhance the severity of dermal lesions following exposure to allergens or irritants. Therefore, it is essential that such products are subject to appropriate clinical evaluation prior to marketing. Consequently, it is important to accurately define a dosing regime in order to assess test products under appropriate conditions. OBJECTIVE: In this study, we extended the use of a standard rubefacient (methyl nicotinate; MN) assay to establish the optimum thickness and duration of action of a novel barrier cream (RD1433). White petroleum jelly (Vaseline(®)) was used as a comparator product. METHODS: The dermal response to MN was measured on the volar forearm skin of volunteers (n = 12; average age 47.5 years) using an array of biophysical instruments and visual scoring. When applied at a nominal thickness of 0.1 mm, RD1433 retained effectiveness against MN for up to six hours. In contrast, Vaseline(®) was relatively ineffective. Moreover, RD1433 provoked no measurable signs of irritation and so can be considered acceptable for further clinical evaluation. CONCLUSION: Future clinical studies using RD1433 should be based on topical application of a 0.1 mm thickness layer every six hours.

Effect of ethnicity, gender and age on the amount and composition of residual skin surface components derived from sebum, sweat and epidermal lipids.

BACKGROUND/PURPOSE: The superficial layer on the skin surface, known as the acid mantle, comprises a mixture of sebum, sweat, corneocyte debris and constituents of natural moisturizing factor. Thus, the phrase 'residual skin surface components' (RSSC) is an appropriate term for the mixture of substances recovered from the skin surface. There is no general agreement about the effects of ethnicity, gender and age on RSSC. The aim of this human volunteer study was to evaluate RSSC in relation to ethnicity, gender and age. A suitable acquisition medium for RSSC collection was identified and samples of RSSC were subsequently analysed using gas chromatography-mass spectrometry (GC-MS) and gravimetry. METHODS: A total of 315 volunteers participated in the study from a range of self-declared ethnic backgrounds. Six acquisition media were compared to determine the most suitable media for RSSC collection. The effect of age, gender and ethnicity on RSSC collection was evaluated by gravimetric analysis while GC-MS was used to determine the composition of RSSC. RESULTS: Of the six candidate materials assessed, cigarette paper provided the most practical and reproducible sample acquisition medium. There was no significant difference in the amount of RSSC collected when based on gender and ethnicity and no significant correlation between RSSC recovery and age. Up to 49 compounds were detected from human RSSC when analysed by GC-MS. CONCLUSIONS: The results of the present study suggest that RSSC can be effectively collected using cigarette paper and analysed by GC-MS. Ethnicity, gender and age had no significant impact on the quantity of RSSC recovered from the skin surface.

Exposure to organophosphorus compounds: best practice in managing timely, effective emergency responses.

Increasing indications, reports and studies demonstrate that threats from the deliberate use of chemical weapons remain high and are evolving. One of the deadliest classes of chemical weapons are the organophosphorus nerve agents. It is now clear that both state and non-state actors have the ability to deploy and use these types of weapons against individuals and the wider civilian population posing a real and significant threat. The objective of this article is to provide an overview of the issues impacting on a timely critical response to the accidental or deliberate release of Organophosphorus Nerve Agents in order to enhance the understanding of their effects and provide guidance on how first responders might better treat themselves or victims of exposure through a discussion of available evidence and best practices for rapid skin decontamination. The article also examines use of the current nomenclature of 'wet' and 'dry' to describe different forms of decontamination. One of the key conclusions of this article is that adequate preparedness is essential to ensuring that responders are trained to understand the threat posed by Organophosphorus Nerve Agents as well as how to approach a contaminated environment. A key aspect to achieving this will be to ensure that generic medical countermeasures are forward-deployed and available, preferably within minutes of a contamination and that first responders know how to use them.