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Formulation technology as a key component in improving hand hygiene practices

      Proper hand hygiene has long been recognized as a primary tool in reducing transmission of health care-acquired infections. Compliance with recommended practices and an increase in the frequency of hand hygiene can have a negative impact on skin condition. Poor skin condition can result in reduced compliance with hand hygiene guidelines. In addition to reduced compliance with proper hand hygiene, deterioration in skin condition leads to reduced barrier function of the skin, changes in skin microflora, and increased shedding of skin squames. Thus, poor skin condition can increase the risk of infection, increase costs to the facility, and reduce the quality of life for the health care worker. To address the problem of skin irritation and its link to low compliance to hand hygiene practices, the Centers for Disease Control and Prevention (CDC) Guideline for Hand Hygiene for Health Care Settings recommends that hand hygiene agents should be well accepted, well tolerated, and formulated to minimize irritancy. Sophisticated formulation technologies and the proper selection of ingredients can provide products that encourage hand hygiene compliance through pleasing aesthetic properties and by overcoming the damaging effects of hand hygiene practices.
      Proper hand hygiene has long been recognized as a primary tool in reducing transmission of health care-acquired infections.
      • Steere A.C.
      • Mallison G.F.
      Handwashing practices for the prevention of nosocomial infections.
      • Daschner F.D.
      Useful and useless hygienic techniques in intensive care units.
      • Larson E.
      • Killien M.
      Factors influencing handwashing behavior of patient care personnel.
      • Seitz J.C.
      • Newman J.L.
      Factors affecting skin condition in two nursing populations: implications for current handwashing protocols.
      This tool had traditionally consisted of handwashing with plain or antiseptic soaps and in more recent years has expanded to include the use of alcohol handrubs.
      • Larson E.L.
      • Eke P.I.
      • Laughon B.E.
      Efficacy of alcohol-based hand rinses under frequent-use conditions.
      Ironically, compliance with recommended practices and the commensurate increase in the frequency of hand hygiene can have a negative impact on skin condition and a resultant decrease in compliance. As compliance decreases, educational programs are instituted to spark improvements in hand hygiene frequency.
      • Bjerke N.B.
      The evolution: handwashing to hand hygiene guidance.
      • Dubbert P.M.
      • Dolce J.
      • Richter W.
      • Miller M.
      • Chapman S.W.
      Increasing ICU staff handwashing: effects of education and group feedback.
      • Jarvis W.R.
      Handwashing—the Semmelweiss lesson forgotten?.
      • Kaplan L.M.
      • McGuckin M.
      Increasing handwashing compliance with more accessible sinks.
      • Larson E.
      • Kretzer E.K.
      Compliance with handwashing and barrier precautions.
      • Larson E.
      • Anderson J.K.
      • Baxendale L.
      • Bobo L.
      Effects of a protective foam on scrubbing and gloving.
      • Pittet D.
      • Mourouga P.
      • Perneger T.V.
      • the Members of the Infection Control Program
      Compliance with handwashing in a teaching hospital.
      • Sproat L.J.
      • Inglis T.J.J.
      A multicentre survey of hand hygiene practice in intensive care units.
      As compliance increases, the damaging effects of many of the products used as part of these infection control programs lead to damaged skin, manifested as dryness, redness, cracking, and scaling.
      • Seitz J.C.
      • Newman J.L.
      Factors affecting skin condition in two nursing populations: implications for current handwashing protocols.
      This sets up the unfortunate cycle involving increases in hand hygiene compliance (frequency), health care worker skin damage, and reduced compliance, which then requires new educational intervention.
      • Steere A.C.
      • Mallison G.F.
      Handwashing practices for the prevention of nosocomial infections.
      • Larson E.
      • Killien M.
      Factors influencing handwashing behavior of patient care personnel.
      • Zimakoff J.
      • Kjelsberg A.B.
      • Larsen S.O.
      • Holstein B.
      A multicenter questionnaire investigation of attitudes toward hand hygiene, assessed by the staff in fifteen hospitals in Denmark and Norway.
      • Kownatzki E.
      Hand hygiene and skin health.
      • Boyce J.M.
      It is time for action: improving hand hygiene in hospitals.
      • Boyce J.M.
      • Kelliher S.
      • Vallande N.
      Skin irritation and dryness associated with two hand-hygiene regimens: soap-and-water hand washing versus hand antisepsis with an alcoholic hand gel.
      • Jarvis W.R.
      Benchmarking for prevention: the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance (NNIS) system experience.
      In addition to reduced compliance with proper hand hygiene, deterioration in skin condition leads to reduced barrier function, changes in skin flora,
      • Larson E.L.
      • Norton Hughes C.A.
      • Pyrek J.D.
      • Sparks S.M.
      • Cagatay E.U.
      • Barkus J.M.
      Changes in bacterial flora associated with skin damage on hands of health care personnel.
      and increased bacterial shedding. Thus, poor skin condition can increase the risk of infection,
      • Conly J.M.
      • Hill S.
      • Ross J.
      • Lertzman J.
      • Louie T.J.
      Handwashing practices in an intensive care unit: the effects of an educational program and its relationship to infection rates.
      • Gales-Vargas R.
      • Bueno-Cavanillas A.
      • Garcia-Martin M.
      Epidemiology, therapy and costs of nosocomial infection.
      increase costs to the facility,
      • Gales-Vargas R.
      • Bueno-Cavanillas A.
      • Garcia-Martin M.
      Epidemiology, therapy and costs of nosocomial infection.
      • Pittet D.
      • Sax H.
      • Hugonnet S.
      • Harbarth S.
      Cost implications of successful hand hygiene promotion.
      • Preston G.A.
      • Larson E.L.
      • Stamm W.E.
      The effect of private isolation rooms on patient care practices, colonization and infection in an intensive care unit.
      and reduce the quality of life for the health care worker.
      • Skoet R.
      • Zachariae R.
      • Agner T.
      Contact dermatitis and quality of life: a structured review of the literature.
      • Dickel H.
      • Bruckner T.M.
      • Schmidt A.
      • Diepgen T.L.
      Impact of atopic skin diathesis on occupational skin disease incidence in a working population.
      • Larson E.
      • Friedman C.
      • Cohran J.
      • Treston-Aurand J.
      • Green S.
      Prevalence and correlates of skin damage on the hands of nurses.
      Effective hand hygiene practices using hand hygiene agents that do not negatively impact skin condition will maintain an adequate skin barrier, sustain compliance obtained through education and training, and, thus, reduce the overall cost of health care.
      • Webster J.
      • Faoagali J.L.
      • Cartwright D.
      Elimination of methicillin-resistant Staphylococcus aureus from a neonatal intensive care unit after hand washing with triclosan.

      The importance of skin condition

      Skin is the primary care interface, acting as a vital boundary between the health care worker and the environment and the patient. Skin performs an important protective function. The architecture of this protective layer is multifaceted and serves as a physical barrier between the body and the external environment. This barrier regulates temperature, maintains moisture, and prevents microbial entry. The outermost layer, the stratum corneum (SC), is in constant interaction with the environment. As the regulator of water flow between the skin and environment, the healthy maintenance of the SC is critical. The removal of fats and oils (defatting) and other protective components from the skin and constant exposure to irritating materials can trigger a cascade effect. These effects may not be apparent immediately but can have long-term consequences on both moisturization and inherent barrier properties of the skin.
      • Kownatzki E.
      Hand hygiene and skin health.
      This damage can further lead to contact dermatitis and other skin diseases.
      • Harding C.R.
      The stratum corneum: structure and function in health and disease.
      Hand health and hand hygiene compliance are inescapably interrelated. If, through education programs and vigilance with infection control practices, hand hygiene compliance increases,
      • Pittet D.
      • Mourouga P.
      • Perneger T.V.
      • the Members of the Infection Control Program
      Compliance with handwashing in a teaching hospital.
      • Lam B.C.C.
      • Lee J.
      • Lau Y.L.
      Hand hygiene practices in a neonatal intensive care unit: a multimodal intervention and impact on nosocomial infection.
      the use of hand hygiene products also increases. If the skin becomes dry and irritated through interaction of those products with health care workers' skin, then compliance with hand hygiene practices may decrease.
      • Larson E.
      • Killien M.
      Factors influencing handwashing behavior of patient care personnel.
      • Zimakoff J.
      • Kjelsberg A.B.
      • Larsen S.O.
      • Holstein B.
      A multicenter questionnaire investigation of attitudes toward hand hygiene, assessed by the staff in fifteen hospitals in Denmark and Norway.
      • Ojajarvi J.
      The importance of soap selection for routine hand hygiene in hospital.
      Thus, those who comply will be less likely to comply in the future, ie, compliance can lead to noncompliance. As a result, sustained compliance becomes difficult to achieve.
      To address this complex problem of skin irritation—low compliance to handwashing—and the negative impact of hand hygiene agents, the Centers for Disease Control and Prevention (CDC) recommended in the Guideline for Hand Hygiene for Health Care Settings that hand hygiene agents should be well accepted, well tolerated, and formulated to minimize irritancy.
      • Centers for Disease Control and Prevention
      Guideline for hand hygiene in health-care settings: recommendations of the Health Care Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force.
      A thorough understanding of skin physiology and the interaction of various ingredients with the skin is therefore important to assess adequately the product contribution to overall skin health.
      The skin is a complex organ made up of many different physical and chemical components that fit well together to protect the body from environmental insult.
      • Harding C.R.
      The stratum corneum: structure and function in health and disease.
      • Idson B.
      Water and the skin.
      The nature of that matrix represents a physical barrier. Poor skin condition can result in aberrant architecture, which in turn is more readily penetrated by outside insults, including microorganisms.
      • Kownatzki E.
      Hand hygiene and skin health.
      • Harding C.R.
      The stratum corneum: structure and function in health and disease.
      • Aly R.
      • Maibach H.
      Factors controlling skin bacterial flora.
      The microbiologic makeup of the resident flora on skin also serves as an impediment to carriage of other organisms.
      • Rotter M.L.
      Hand washing and hand disinfection.
      • Larson E.
      Effects of handwashing agent, handwashing frequency and clinical area on hand flora.
      • Reybrouck G.
      Role of the hands in the spread of nosocomial infections.
      In addition to the physical character of the barrier being affected, when skin is damaged, important chemicals can be more readily leeched from within the skin matrix. This can cause a shift in both skin lipids and pH of the skin
      • Bechor R.
      • Zlotogorski A.
      • Dikstein S.
      Effect of soaps and detergents on the pH and casual lipid levels of the skin surface.
      • Dineen P.
      • Hildick-Smith G.
      Antiseptic care of the hands.
      • Fluhr J.W.
      • Bankova L.
      • Elias P.
      Stratum corneum pH and ions- distribution and importance.
      and thus a shift in the environment that is balanced to support a specific resident flora.
      • Aly R.
      • Maibach H.
      Factors controlling skin bacterial flora.
      • Dineen P.
      • Hildick-Smith G.
      Antiseptic care of the hands.
      This damage to skin can result in a change in both the numbers and types of bacteria present. Skin damaged by high-frequency handwashing has been shown to harbor increased levels of organisms.
      • Larson E.L.
      • Norton Hughes C.A.
      • Pyrek J.D.
      • Sparks S.M.
      • Cagatay E.U.
      • Barkus J.M.
      Changes in bacterial flora associated with skin damage on hands of health care personnel.
      • Larson E.
      Effects of handwashing agent, handwashing frequency and clinical area on hand flora.
      • Ojajarvi J.
      • Makela P.
      • Rantasalo I.
      Failure of hand disinfection with frequent hand washing: a need for prolonged field studies.
      • Walter C.W.
      Disinfection of hands.
      • Masako K.
      • Yusuke K.
      • Hideyuki I.
      • Atsuko M.
      • Yoshiki M.
      • Kayoko M.
      • et al.
      A novel method to control the balance of skin micro flora: part 2. A study to assess the effect of a cream containing farnesol and xylitol on atopic dry skin.
      • Larson E.
      Handwashing and skin physiologic and bacteriologic aspects.
      Flora can shift from gram-positive bacteria to higher levels of gram-negative bacteria.
      • Larson E.
      • Leyden J.J.
      • McGinley K.J.
      • Grove G.L.
      • Talbot G.H.
      Physiologic and microbiologic changes in skin related to frequent handwashing.
      Along with this shift toward increased levels of gram-negative bacteria, greater antibiotic resistance of the remaining gram-positive organisms has also been demonstrated.
      • Larson E.L.
      • Norton Hughes C.A.
      • Pyrek J.D.
      • Sparks S.M.
      • Cagatay E.U.
      • Barkus J.M.
      Changes in bacterial flora associated with skin damage on hands of health care personnel.
      • Larson E.
      • Leyden J.J.
      • McGinley K.J.
      • Grove G.L.
      • Talbot G.H.
      Physiologic and microbiologic changes in skin related to frequent handwashing.
      As well as reduced barrier properties, a shift in the skin's ecologic environment, and changes in the numbers and types of bacteria, an increase in skin shedding usually accompanies diminishing skin condition.
      • Larson E.
      Handwashing and skin physiologic and bacteriologic aspects.
      • McGinley K.J.
      • Marples R.R.
      • PLewig G.
      A method for visualizing and quantitating the desquamating portion of the human stratum corneum.
      • Larson E.
      Current handwashing issues.
      • Larson E.
      • McGinley K.J.
      • Grove G.L.
      • Leyden J.J.
      • Talbot G.H.
      Physiologic, microbiologic, and seasonal effects of handwashing on the skin of health care personnel.

      Watt B. Shedding our skin. Microbiol Sci 19874:79.

      • Maki D.G.
      The use of antiseptics for handwashing by medical personnel.
      • Noble W.C.
      Dispersal of skin microorganisms.
      • Mackintosh C.A.
      Skin Scales and microbial contamination.
      These skin squames can contain large numbers of microorganisms, thus dispersing organisms into the health care environment as the skin sheds.
      • Larson E.
      • Leyden J.J.
      • McGinley K.J.
      • Grove G.L.
      • Talbot G.H.
      Physiologic and microbiologic changes in skin related to frequent handwashing.
      • Maki D.G.
      The use of antiseptics for handwashing by medical personnel.
      • Noble W.C.
      Dispersal of skin microorganisms.
      • Mackintosh C.A.
      Skin Scales and microbial contamination.
      • Meers P.D.
      • Yeo G.A.
      Shedding of bacteria and skin squames after handwashing.

      Heldman DR, Sunga FE CA, Hedrick TI. Microorganism shedding by human beings. Contam Control 1967;6:28-31.

      Factors influencing skin condition

      The skin condition of the health care worker is a complicated subject and is influenced by many factors
      • Seitz J.C.
      • Newman J.L.
      Factors affecting skin condition in two nursing populations: implications for current handwashing protocols.
      • Larson E.
      • McGinley K.J.
      • Grove G.L.
      • Leyden J.J.
      • Talbot G.H.
      Physiologic, microbiologic, and seasonal effects of handwashing on the skin of health care personnel.
      (Fig 1). These factors include frequency and types of products utilized, glove usage (eg, occlusion, latex, and powder), ingredients in products used, age, season and location (climate). A number of these factors cannot be controlled (such as age, season, and location), and, therefore, it is essential to mitigate and control those variables that can be controlled, to break the cycle of reduced compliance.
      • Seitz J.C.
      • Newman J.L.
      Factors affecting skin condition in two nursing populations: implications for current handwashing protocols.
      • Boyce J.M.
      • Kelliher S.
      • Vallande N.
      Skin irritation and dryness associated with two hand-hygiene regimens: soap-and-water hand washing versus hand antisepsis with an alcoholic hand gel.
      Figure thumbnail gr1
      Fig 1Factors influencing skin condition.
      The use of gloves has significantly increased with the adoption of universal precautions. Gloves can impact skin condition in a number of ways, both physically and chemically.
      • Hamann C.P.
      • Kick S.A.
      Diagnosis-driven management of natural rubber latex glove sensitivity.
      • Taylor J.S.
      Other reactions from gloves.
      Friction injury because of interaction of the glove with the skin surface can result in physical damage to the SC. The reaction of a health care worker to the ingredients that make up the glove (latex, nitrile, or powder within the glove) can result in substantial irritation and/or allergic reaction. Ingredients under occlusion can also engender greater irritation response.
      • Kownatzki E.
      Hand hygiene and skin health.
      • Wahlberg J.E.
      Irritation and contact dermatitis from protective gloves- an overview.
      The use of gloves and the occlusion of the skin can also result in swelling of the horny layer, which can in turn release water-soluble inflammatory substances normally found within this layer, triggering a downward spiral toward dermatitis.
      • Kligman A.M.
      Hydration injury to human skin.
      Thus, the impact of poor skin condition is magnified with increased glove use.
      • Larson E.
      • Friedman C.
      • Cohran J.
      • Treston-Aurand J.
      • Green S.
      Prevalence and correlates of skin damage on the hands of nurses.
      Hand hygiene practices (frequency of use and product type used) are in good part driven by the condition of the skin of the person using them.
      • Ojajarvi J.
      The importance of soap selection for routine hand hygiene in hospital.
      • Pittet D.
      Improving compliance with hand hygiene in hospitals.
      However, skin condition is derived from the product choices made.
      • Larson E.L.
      • Eke P.I.
      • Laughon B.E.
      Efficacy of alcohol-based hand rinses under frequent-use conditions.
      • Jeanes A.
      Handwashing: what is the best solution?.
      • Boyce J.M.
      Antiseptic technology: access, affordability, and acceptance.
      • Larson E.
      • Silberger M.
      • Jakob K.
      • Whittier S.
      • Lai L.
      • Della Latta P.
      • et al.
      Assessment of alternative hand hygiene regimens to improve skin health among neonatal intensive care unit nurses.
      There are 3 main types of products used as part of a hand hygiene regimen: cleansers, alcohol hand sanitizers, and lotions.
      • Held E.
      • Agner T.
      Effect of moisturizers on skin susceptibility to irritants.
      • Larson E.L.
      • Eke P.I.
      • Wilder M.P.
      • Laughon B.E.
      Quantity of soap as a variable in handwashing.
      The composition of these products and the frequency of their use will have significant impact on the skin condition of the health care worker.
      • Ojajarvi J.
      The importance of soap selection for routine hand hygiene in hospital.
      • Larson E.L.
      • Aiello A.E.
      • Bastyr J.
      • Lyle C.
      • Stahl J.
      • Cronquist A.
      • et al.
      Assessment of two hand hygiene regimens for intensive care unit personnel.
      • Cohen B.
      • Saiman L.
      • Cimiotti J.
      • Larson E.
      Factors associated with hand hygiene practices in two neonatal intensive care units.
      • Winnefeld M.
      • Richard M.A.
      • Drancourt M.
      • Grob J.J.
      Skin tolerance and effectiveness of two hand decontamination procedures in everyday hospital use.
      • Mayer J.A.
      • Dubbert P.M.
      • Miller M.
      • Burkett P.A.
      • Chapman S.W.
      Increasing handwashing in an intensive care unit.

      Held E, Mygind K, Wolff C, Gyntelberg F, Agner T. Prevention of work related skin problems: an intervention study in wet work employees. Occup Environ Med 002;59:556-61.

      The CDC makes recommendations in the Guideline for Hand Hygiene for Health Care Settings
      • Centers for Disease Control and Prevention
      Guideline for hand hygiene in health-care settings: recommendations of the Health Care Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force.
      that include indications for the use of all 3 of these product types. Numerous studies have demonstrated that the use of product regimens is more effective and better tolerated by the skin than soap and water alone.
      • Conly J.M.
      • Hill S.
      • Ross J.
      • Lertzman J.
      • Louie T.J.
      Handwashing practices in an intensive care unit: the effects of an educational program and its relationship to infection rates.
      • Ojajarvi J.
      The importance of soap selection for routine hand hygiene in hospital.
      • Meers P.D.
      • Yeo G.A.
      Shedding of bacteria and skin squames after handwashing.
      • Rieger M.
      Human epidermis responses to sodium lauryl sulfate exposure.
      • Jones R.D.
      • Jampani H.B.
      • Newman J.L.
      • Lee A.S.
      Triclosan: a review of effectiveness and safety in health care settings.
      The appropriate choice and use of all of these products (mild cleansing agents, moisturizing alcohol hand sanitizers, and moisturizing lotions
      • Held E.
      • Agner T.
      Effect of moisturizers on skin susceptibility to irritants.
      • McCormick R.D.
      • Buchman T.L.
      • Maki D.G.
      Double-blind, randomized trial of scheduled use of a novel barrier cream and an oil-containing lotion for protecting the hands of health care workers.
      • Held E.
      • Sveinsdottir S.
      • Agner T.
      Effect of long-term use of moisturizer on skin hydration, barrier function and susceptibility to irritants.
      • Hannuksela M.
      Moisturizers in the prevention of contact dermatitis.
      • Berndt U.
      • Wigger-Alberti W.
      • Gabard B.
      • Elsner P.
      Efficacy of a barrier cream and its vehicle as protective measures against occupational irritant contact dermatitis.
      ) can result in significant mitigation of negative impacts on skin condition.
      • Larson E.
      • Friedman C.
      • Cohran J.
      • Treston-Aurand J.
      • Green S.
      Prevalence and correlates of skin damage on the hands of nurses.
      • Larson E.
      Skin hygiene and infection prevention: more of the same or different approaches?.
      It is important to understand that product formulation of hand hygiene agents utilized as part of any skin care regimen can have significant effects on skin. It is not just the active ingredients that impact skin condition but the inactive ingredients as well. Therefore, for informed product choices to be made, the evaluation of the total formulation (product) on human skin is necessary to assess properly the acceptability for use in the health care environment.

      Measurements of skin condition

      In the same way that compliance with hand hygiene practices should be monitored to assure that proper procedures are followed and to measure their effectiveness at reducing infection, hand hygiene products should be evaluated for proper ingredient inclusion and to measure their effectiveness at maintaining skin health. To assess accurately the impact of various products on skin health, a variety of test methodologies are used. These test methods use a number of instrumental and visual assessment techniques to quantify parameters important for good skin health, including both visual markers and physical properties. These can include measurement of moisture levels, barrier function, skin redness, dryness, and swelling.

      Methods

      Inherent irritation or sensitization potential is typically assessed using either animal or human subjects and a method involving products or ingredients left in contact with the skin surface for extended periods of time. The skin is assessed for a physical reaction in the form of redness or swelling. These include tests for primary skin irritation, sensitization, and hypoallergenicity.
      The Forearm Controlled Application Test (FCAT) has been used primarily for assessing drying (and conversely moisturization) potential of skin care products. It involves the application of products in the manner in which they would be used and utilizes the volar forearm of a subject. The surface area and relative flatness of this surface allows for multiple products to be evaluated side by side on the same subject.
      • Ertel K.D.
      • Keswick B.H.
      • Bryant P.B.
      A forearm controlled application technique for estimating the relative mildness of personal cleansing products.
      This type of study also has the benefit of the subject's skin serving as its own control. Products are then compared either with each other and/or with untreated or control sites (where only water has been applied) using measurements generated utilizing various instrumentation and/or visual evaluation.
      • Draelos Z.D.
      Formulating for sensitive skin.
      Later discussion within this article utilized data generated using this testing technique to emphasize various points in an evidence-based manner. To aid in evaluation of those specific studies presented in this review, a generalized procedure follows. Subject numbers and applications techniques will be outlined in the Figure legends accompanying the graphs within the appropriate sections.

      Subjects

      The subjects were volunteers, male and female, ages 18 to 65 years. All subjects completed a 5-day conditioning period utilizing a marketed bar soap product in place of their normal cleansing product. All subjects were to avoid the use of creams, lotions, ointments, and powders on the forearms. All subjects were only accepted into the study with dryness scores of <3 prior to the first treatment for washing studies and ≤2 for leave-on application studies. No subject could be currently participating in another study or have participated in another study within the previous 4 weeks. Other exclusion criteria were insulin-dependant diabetes; obvious skin pathology; and use of corticosteroid, antihistamine, or antiinflammatory medications. No subject with allergies to article components, soaps, latex, or fragrances was allowed to participate.

      Procedure

      For the testing of cleansing products, the treatment phase consisted of 2 washing sessions of 2 washes each, daily for 4 days with a morning session on the fifth day. Washing was done on 3 test sites per volar forearm, 3 cm in diameter. Assignment of test sites was done utilizing a Latin square design randomization. Each site was wet with running water (34°C-39°C), and the requisite product was applied volumetrically. The bar soap was applied by stroking a masslinn towel across the bar for 6 seconds and transferring the lather to the test site with the towel. Test sites were washed for 10 seconds, the lather allowed to sit for 90 seconds and rinsed for 15 seconds, then blotted dry. Visual observations were made prior to each morning (including initial baselines prior to the first wash) session, with visual and instrumental analysis made 3 hours after the final wash on day 5.
      For the testing of leave-on products (lotions, alcohol rubs), the treatment phase consisted of a washing session of 1 wash of Ivory soap (Proctor and Gamble, Cincinnati, OH), 30 minutes prior to the application of test articles to dry out the skin. Each site was wet with running water (98°F ± 5°F) for 5 seconds, the bar lathered for 10 seconds, and the forearms washed for 20 seconds. The forearms were then rinsed for 20 seconds and gently dried with a disposable towel. After a 30-minute waiting period, baseline evaluations were conducted. After baseline evaluations, the test article was applied volumetrically to a 3-cm-diameter test site (foam products were applied first to weight boat on a balance, weighed, and then applied). Assignment of test sites was randomized utilizing a complete block design. Test sites were rubbed for 60 seconds. The instrumental evaluation for moisture levels in the skin was measured at baseline (just prior to application of test articles) and at varying times after application utilizing the instrumentation noted in the figure legends. Readings were taken in a room maintained at 70°F (±2°F) and 30% to 50% relative humidity following a 30-minute equilibration period. Three replicates of each reading were taken.

      Statistical analysis

      Data used for statistical analysis were changes from baseline. Within-treatment analysis was conducted using Wilcox signed rank test. Instrumental data were analyzed using the Student t test for paired data. The significance level of .05 was employed.

      Assessments

      Clinical studies can also involve the use of the products in an actual health care environment. Assessments are made on subjects using the products as part of their everyday activities under actual in-use situations.
      Technology enables clinicians to measure the impact of a given formulation/product on skin health. The variety of tools currently available offers a multidimensional approach to understanding subtle, often invisible changes that can impact the skin's function. A variety of parameters, such as hydration and barrier function, and visual assessment of dryness and redness, can be done on the same test site.
      A trained evaluator assesses the skin surface using magnification of at least ×3. The dryness and erythema scores usually range from 0 to 6. Zero is considered normal with no observable scale or irritation. A score of 6 indicates extensive cracking of skin surface and widespread reddening of the skin. Assessments can also be made with the aid of high-resolution photography, by which the increased image resolution allows for the ability to differentiate between normal and damaged skin at a very low level.
      Transepidermal water loss (TEWL) reflects the integrity of the SC water barrier and can be an indicator of skin damage.
      • van der Valk P.G.M.
      • Kucharekova M.
      • Tupker R.A.
      Transepidermal water loss and its relation to barrier function and skin irritation.
      It is the classic technique used to determine the disruption to the skin barrier by soap and surfactants, alcohols, or other various treatments.
      • Rogiers V.
      • Houben E.
      • De Paepe K.
      Transepidermal water loss measurements in dermato-cosmetic science.
      TEWL is measured with an evaporimeter. This instrument can detect changes in the skin integrity before they become visually apparent.
      • Primvera G.
      • Fluhr J.W.
      • Berardesca E.
      Standardization of measurements and guidelines.
      It utilizes a humidity sensor to record the rate of water loss from the skin. Relative increases in TEWL values are indicative of skin barrier damage.
      Various instruments have been designed to measure moisture content of the SC. The electrical conductance, capacitance, or impedance of the skin surface is measured by these types of instruments.
      • Blichmann C.W.
      • Serup J.
      Assessment of skin moisture: measurement of electrical conductance, capacitance and transepidermal water loss.
      • Leveque J.L.
      • De Rigal J.
      Impedance methods for studying skin moisturization.
      • Khazaka G.
      Assessment of stratum corneum hydration: corneometer CM825.
      • Wickett R.
      Hardware and measuring principles: the NOVA dermal phase meter.
      • Primvera G.
      • Fluhr J.W.
      • Berardesca E.
      Electrical assessment of skin hydration: standardization of measurements and guidelines.
      • Bernengo J.C.
      • de Rigal J.
      Physical methods of measuring stratum corneum water content in vivo.
      The measurements of these “moisture meters” have been demonstrated to correlate to water content in the SC.
      • Lawler J.C.
      • Davis M.J.
      • Griffith E.C.
      Electrical characteristics of the skin: the impedance of the surface sheath and deep tissues.
      • Tagami H.
      • Ohi M.
      • Iwatsuki K.
      • Kanamaru Y.
      • Yamada M.
      • Ichijo B.
      Evaluation of the skin surface hydration in vivo by electrical measurement.
      • Tagami H.
      Meaurement of electrical conductance and impedance.
      The values decrease as the skin dries out because of moisture loss and increase as moisture content in the SC increases. Therefore, undesirable negative changes in the water content of the SC results in a lower or diminishing reading. The selection of instruments is usually made based on the range of moisture content (ie, dry vs very moist skin).
      • Lee C.M.
      • Maibach H.I.
      Bioengineering analysis of water hydration: an overview.
      A variety of other physical and chemical properties of skin can also be quantified, including elasticity, topography, and measurement of chemical compounds typically found within the skin matrix, such as natural moisturizing factors.

      Impact of formulation on skin condition

      To be able to maintain healthy skin under the stress conditions (listed earlier) that exist in a health care environment, the products used must be designed to both work well for the intended function (cleansing, antimicrobial efficacy, moisturization) and to be kind to the skin. As health care workers comply with appropriate guidelines and utilize infection control products, it is important to encourage their continued use through acceptable aesthetics and positive impact on skin health.
      • Pittet D.
      • Hugonnet S.
      • Harbarth S.
      • Mourouga P.
      • Sauvan V.
      • Touveneau S.
      • et al.
      Effectiveness of a hospital-wide programme to improve compliance with hand hygiene.
      If skin becomes dry and irritated, compliance with appropriate infection control guidelines will decrease.
      • Seitz J.C.
      • Newman J.L.
      Factors affecting skin condition in two nursing populations: implications for current handwashing protocols.
      • Pittet D.
      Improving compliance with hand hygiene in hospitals.
      Therefore, the products used as part of a comprehensive infection control program must contain ingredients with characteristics that make them appropriate choices for a given formulation, and they must function well together.
      • Fluhr J.W.
      • Rigano L.
      Clinical effects of cosmetic vehicles on skin.
      Thus, evaluation of any product formulation should include review of the individual ingredients as well as data generated on testing of the total formulation.
      • Draelos Z.D.
      Formulating for sensitive skin.
      Milder surfactants and antimicrobials, as well as the use of skin conditioning agents that redeposit moisture and/or refat the skin, can have an influence on skin condition and significantly mitigate the drying effects of cleansers
      • Ananthapadmanabhan K.P.
      • Moore D.J.
      • Subramanyan M.M.
      • Meyer F.
      Cleansing without compromise: the impact of cleansers on the skin barrier and the technology of mild cleansing.
      and alcohol.
      The use of formulation technologies offers the opportunity to break the cycle of noncompliance by controlling the types and amounts of ingredients that are used on the skin. Formulation technology can help provide products with pleasing aesthetic properties (also recognized as an important factor in encouraging proper hand hygiene) that do not negatively impact skin condition and novel product forms that provide innovative strategies for encouraging hand hygiene.

      Ingredients

      Antiseptic agents

      Antimicrobial-containing products are used in situations in which increased reductions of organisms on the skin (compared with plain soap and water cleansing) are desired.
      • Larson E.
      • Mayur K.
      • Laughon B.A.
      Influence of two handwashing frequencies on reduction in colonizing flora with three handwashing products used by health care personnel.
      Antimicrobial agents can cause irritation, either directly or through the choice of other ancillary ingredients (eg, a defatting or irritating surfactant) that are mandated by compatibility issues with the antimicrobial agent. Certain antimicrobial agents can also cause sensitization in some users. Although active ingredients can cause irritation or sensitization in some instances, it is important to understand that it is the formulation as a whole that impacts skin health. In many cases, the antimicrobial ingredient plays little or no part in the irritation or dryness experienced when using hand hygiene products. It is the “inactive” ingredients in a formulation, such as cleansing agents or the lack of moisturizing agents, as much as any active ingredient, that can have the greatest impact.
      Iodophors were initially developed to provide a “tamed” form of iodine, a well-established antiseptic agent. However, no matter how “tamed” the form of iodine is, this active still functions through oxidizing chemistry, so the list of ingredients that are compatible with this chemistry are narrow. This limits the surfactants and skin-conditioning agents that can be used in combination with iodophor compounds. Unfortunately, this compromise produces an antimicrobial with reduced clinical efficacy in combination with less aesthetically pleasing and relatively irritating overall formulations that still possess sensitization potential.
      • McGinley K.J.
      • Marples R.R.
      • PLewig G.
      A method for visualizing and quantitating the desquamating portion of the human stratum corneum.
      • Faoagali J.
      • Fong J.
      • George N.
      • Mahoney P.
      • O'Rourke V.
      Comparison of the immediate, residual, and cumulative antibacterial effects of Novaderm R, Novascrub R, Betadine Surgical Scrub, Hibiclens, and liquid soap.
      • Kozuka T.
      Patch testing to exclude allergic contact dermatitis caused by povidone-iodine.
      • Maki D.G.
      • Hecht J.A.
      Comparative study of handwashing with chlorhexidine, povidone-iodine, and nongermicidal soap for prevention of nosocomial infection.
      These characteristics, as well as staining issues, have limited iodophor use to primarily surgical scrub and prep applications.
      • Georgiade G.S.
      • Georgiade N.G.
      • Grandy R.P.
      • Goldenheim P.D.
      The effect of povidone-iodine solutions used as surgical preparations on the bacterial flora of the skin.
      Chlorhexidine gluconate (CHG) is a cationic molecule with good substantivity to skin.
      • Denton G.W.
      Chlorhexidine.
      This skin substantivity makes CHG-based products exceptionally good at providing the cumulative and persistent activity that is a required or desirable attribute for specific health care applications.
      • Denton G.W.
      Chlorhexidine.
      • Scott D.
      • Barnes A.
      • Lister M.
      • Arkell P.
      An evaluation of the user acceptability of chlorhexidine handwash formulations.
      CHG is inherently mild to the skin, based on available data.
      • Rosenberg A.
      • Alatary S.D.
      • Peterson A.F.
      Safety and efficacy of the antiseptic chlorhexidine gluconate.
      This combination of substantivity and mildness has made CHG a popular choice as an antimicrobial agent used in health care environments. However, the cationic nature of CHG that makes the skin-binding characteristic possible also limits the cleansing formulations that utilize it as an active ingredient because it can only be formulated with a relatively small list of compatible surfactants that do not generally foam well.
      • Denton G.W.
      Chlorhexidine.
      As a result, some formulations of CHG cleansers have included higher concentrations of surfactants to generate foam, a desirable attribute for skin cleansers.
      • Scott D.
      • Barnes A.
      • Lister M.
      • Arkell P.
      An evaluation of the user acceptability of chlorhexidine handwash formulations.
      These higher levels of surfactants tend to defat the skin with frequent use. Other approaches have used surfactants that have higher intrinsic foam but are less mild. As a result, CHG cleansing formulations have historically not been able to realize fully the fundamental potential of CHG-based cleansers to deliver the best skin compatibility. CHG can also be a sensitizer to a small portion of the population.
      • Kozuka T.
      Patch testing to exclude allergic contact dermatitis caused by povidone-iodine.
      • Thune P.
      Two patients with chlorhexidine allergy—naphylactic reactions and eczema.
      • Garvey L.H.
      • Roed-Petersen J.
      • Husum B.
      Anaphylactic reactions in anaesthetised patients—four cases of chlorhexidine allergy.
      Alcohols can defat the skin,
      • Gould D.
      Bacterial infections: antibiotics and decontamination.
      • Haan P.D.
      • Meester H.H.M.
      • Bruynzeel D.P.
      Irritancy of alcohols.
      an effect even more pronounced when used in rinse-off applications. However, data indicate that alcohols applied to the skin in a leave-on application produce little irritation when properly formulated.
      • Larson E.L.
      • Eke P.I.
      • Laughon B.E.
      Efficacy of alcohol-based hand rinses under frequent-use conditions.
      • Newman J.L.
      • Seitz J.C.
      Intermittent use of an antimicrobial hand gel for reducing soap-induced irritation of health care personnel.
      This is presumably due to the fact that lipids momentarily solubilized by alcohol are immediately redeposited to the skin as the alcohol evaporates. This evaporative property of alcohol also limits its persistence.
      • Centers for Disease Control and Prevention
      Guideline for hand hygiene in health-care settings: recommendations of the Health Care Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force.
      • Ayliffe G.A.J.
      • Babb J.R.
      • Quoraishi A.H.
      A test for ‘hygienic’ hand disinfection.
      • Ayliffe G.A.J.
      • Babb J.R.
      • Davies J.G.
      • Lilly H.A.
      Hand disinfection: a comparison of various agents in laboratory and ward studies.
      However, some formulations overcome this limitation though the inclusion of evaporation retardants and other agents that can extend and enhance activity.
      • Food and Drug Administration
      Tentative final monograph for healthcare antiseptic drug products; proposed rule.
      Alcohols can also enhance the penetration of skin-conditioning agents and other antiseptic agents. There have been suggestions that alcohol types vary in their skin compatibility properties, but there is little evidence to substantiate those views.
      • De Haan P.
      • Meester H.H.M.
      • Bruynzeel D.P.
      Irritancy of alcohols.
      When formulation effects are taken into account, there seems to be little difference in skin compatibility among alcohols.
      • Lubbe J.
      • Ruffieux C.
      • Van Melle G.
      • Perrenoud D.
      Irritancy of the skin disinfectant n-propanol.
      • Timmer C.
      Disinfectants.
      Triclosan is widely used as an antiseptic agent in professional health care and household products.
      • Jones R.D.
      • Jampani H.B.
      • Newman J.L.
      • Lee A.S.
      Triclosan: a review of effectiveness and safety in health care settings.
      • Bhargava H.N.
      • Leonard P.A.
      Triclosan: applications and safety.
      • Bendig J.W.
      Surgical hand disinfection: comparison of 4% chlorhexidine detergent solution and 2% triclosan detergent solution.
      Triclosan has low inherent irritation potential and is not known to produce sensitizing effects.
      • Jones R.D.
      • Jampani H.B.
      • Newman J.L.
      • Lee A.S.
      Triclosan: a review of effectiveness and safety in health care settings.
      • Bhargava H.N.
      • Leonard P.A.
      Triclosan: applications and safety.
      In fact, studies suggest that triclosan exhibits antiinflammatory properties in human tissue.
      • Jones R.D.
      • Jampani H.B.
      • Newman J.L.
      • Lee A.S.
      Triclosan: a review of effectiveness and safety in health care settings.
      • Hannuksela M.
      Moisturizers in the prevention of contact dermatitis.
      • Bhargava H.N.
      • Leonard P.A.
      Triclosan: applications and safety.
      • Coleman E.J.
      • Espositio A.
      • Afflitto J.
      • Gaffar A.
      Triclosan prevents SLS-cytotoxicity to human gingival fibroblasts.
      This active ingredient is substantive to the skin as a result of binding to epidermal lipid components. These properties make triclosan a preferred choice for antiseptic cleansing formulations and provide good user acceptance. However, the antiseptic efficacy of triclosan can be dramatically affected by formulation properties because it can be trapped by surfactant micelles.
      • Jones R.D.
      • Jampani H.B.
      • Newman J.L.
      • Lee A.S.
      Triclosan: a review of effectiveness and safety in health care settings.
      Optimizing activity, while maintaining low irritation and positive aesthetic properties, presents a significant formulation challenge.
      A variety of other less common antiseptic agents are also used in health care settings around the world.
      • Centers for Disease Control and Prevention
      Guideline for hand hygiene in health-care settings: recommendations of the Health Care Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force.
      Although these agents vary in inherent mildness, in almost every case, the observed irritation potential and acceptability of specific products are highly formulation specific.

      Surfactants

      Surfactants (surface-active agents) are multifunctional ingredients that have the ability to reduce surface or interfacial tension. They perform this function by lining up at an interface. They can act as wetting agents by reducing the surface tension of water (lowering the tendency to “bead up” and allowing “spread” on a surface). They can act as cleansing agents by emulsifying or solubilizing soils and exhibiting lathering properties. They can perform as emulsifiers to create and maintain dispersed droplets of one liquid in another (lotions, creams). They can also serve as hydrotropes (increasing the solubility of other less water-soluble surfactants) and soil-suspending agents.
      The very nature of cleansing products can make them irritating to the skin.
      • Hannuksela M.
      Moisturizers in the prevention of contact dermatitis.
      • Zhou J.
      • Mark R.
      • Stoudemayer T.
      • Sakr A.
      • Lichtin J.L.
      • Gabriel K.L.
      The value of multiple instrumental and clinical methods, repeated patch applications, and daily evaluations for assessing stratum corneum changes induced by surfactants.
      • Tupker R.A.
      Detergents and cleansers.
      • Wilhelm K.P.
      Prevention of surfactant-induced irritant contact dermatitis.
      • Pierard-Franchimont C.
      • Goffin V.
      • Pierard G.E.
      Comparative stratum corneum tolerance to antiseptic cleansing products.
      The act of removing soil from the skin surface seems in conflict with maintaining adequate moisture and lipid levels. However, the choice of ingredients is critical to being able to walk the fine line between soil and organism removal and skin irritation and dryness. The damaging effects of high-frequency handwashing results from both the inherent irritation characteristics and stripping (defatting) properties of the product used and the damaging effects of water.
      • Morganti P.
      Natural soap and syndet bars.
      • Paye M.
      • Cartiaux Y.
      • Goffin V.
      • Pierard G.E.
      Hand and forearm skin: comparison of their respective responsiveness to surfactants.
      By solubilizing or disrupting the lipids that help maintain healthy water content and normal skin physiology, negative impact on skin condition can result. In cleansing products, the ingredients performing soil removal are surfactants. The right choice of surfactants, as well as the inclusion of proper moisturizing agents, can prevent or dramatically lessen the dryness and irritation associated with the act of washing.
      • Ananthapadmanabhan K.P.
      • Moore D.J.
      • Subramanyan M.M.
      • Meyer F.
      Cleansing without compromise: the impact of cleansers on the skin barrier and the technology of mild cleansing.
      This is accomplished by using surfactants that are mild, that are not defatting, and that rinse well from the skin surface.
      • Larson E.L.
      • Eke P.I.
      • Laughon B.E.
      Efficacy of alcohol-based hand rinses under frequent-use conditions.
      There are many surfactants that are well-known to be irritating to skin.
      • Wilhelm K.P.
      Prevention of surfactant-induced irritant contact dermatitis.
      • Prottey C.
      • Ferguson T.
      Factors which determine the skin irritation potential of soaps and detergents.
      • Emilson A.
      • Lindberg M.
      • Forslind B.
      The temperature effect on in vitro penetration of sodium lauryl sulfate and nickel chloride through human skin.
      These tend to be prevalent in consumer products because they foam and clean well and are inexpensive for the manufacturing company.
      • Rieger M.
      Human epidermis responses to sodium lauryl sulfate exposure.
      In a consumer home setting, the limited numbers of times these products are used during a day makes the negative properties of these surfactants less apparent and of less significance than in a health care setting. However, based on their inherent skin binding, irritation, and/or defatting characteristics,
      • Larson E.L.
      • Eke P.I.
      • Laughon B.E.
      Efficacy of alcohol-based hand rinses under frequent-use conditions.
      • Prottey C.
      • Ferguson T.
      Factors which determine the skin irritation potential of soaps and detergents.
      • Zatz J.L.
      Modification of skin permeation by surfactants.
      • Gloor M.
      • Wasik B.
      • Gehring W.
      • Grieshaber R.
      • Kleesz P.
      • Fluhr J.W.
      Cleansing, dehydrating, barrier-damaging and irritating hyperaemising effect of four detergent brands: comparative studies using standardized washing models.
      these surfactants are not generally appropriate to be used as the primary surfactants in products used for the health care environment in which caregivers can wash their hands upward of 50 times per day.
      Defatting cleansers can remove lipids from the skin during washing.
      • Bechor R.
      • Zlotogorski A.
      • Dikstein S.
      Effect of soaps and detergents on the pH and casual lipid levels of the skin surface.
      • Ananthapadmanabhan K.P.
      • Moore D.J.
      • Subramanyan M.M.
      • Meyer F.
      Cleansing without compromise: the impact of cleansers on the skin barrier and the technology of mild cleansing.
      • Prottey C.
      • Ferguson T.
      Factors which determine the skin irritation potential of soaps and detergents.
      Surfactants can solubilize or disrupt the lipids that help maintain healthy water content and normal skin physiology. Disruption of the lipid layer of the skin can result in excessive water evaporation and removal of the skin's natural moisturizing factors and can lead to dry and irritated hands. This is the case for both nonantimicrobial and antimicrobial cleansing products. The drying and irritation effects seen with the use of some skin antiseptics can be attributed to the use of defatting surfactants rather than the antimicrobial agent itself.
      Even in those instances when the fatty acid level in the skin is maintained, some surfactants bind to the skin surface more readily and possess greater irritation potential.
      • Zatz J.L.
      Modification of skin permeation by surfactants.
      • Ananthapadmanabhan K.P.
      • Yu K.K.
      • Meyers C.L.
      • Aronson M.P.
      Binding of surfactants to stratum corneum.
      • Ohlenschlaeger J.
      • Friberg J.
      • Ramsing D.
      • Agner T.
      Temperature dependency of skin susceptibility to water and detergents.
      Surfactants such as amphoacetates, amphodiacetates, sulfoscuccinates, and isethionates are significantly milder and a more appropriate choice for use as primary surfactants in health care products.
      One can learn which surfactants have inherent mildness characteristics by comparing the primary irritation index for individual components (Fig 2). This index compares the irritation reaction (a combination of swelling and redness) for ingredients in contact with the skin for an extended period of time. Each score is both an addition of multiple evaluations and an average over multiple test subjects. Thus, the higher the irritation score, the more inherently irritating is the surfactant. Therefore, the amount of ingredients in a formulation with high primary irritation index scores should be minimized or eliminated. Blending of milder surfactants with those that are inherently more irritating can also provide increased mildness.
      Figure thumbnail gr2
      Fig 2Mean primary irritation (PII) score for commonly used surfactants. Data adapted from Schoenberg T. Formulating mild foaming bath products, Cosmetics and Toiletries. Vol. 100, No. 5, page 53. ∗∗Individual surfactant supplier literature, “Jordaopon Cocoyl Isethionates,” printed in the USA January 1995 by PPG Specialty Chemicals, Gurnee, Illinois.
      In vivo testing of cleansing products is also an important part of defining mildness of a given formulation.
      • Zhou J.
      • Mark R.
      • Stoudemayer T.
      • Sakr A.
      • Lichtin J.L.
      • Gabriel K.L.
      The value of multiple instrumental and clinical methods, repeated patch applications, and daily evaluations for assessing stratum corneum changes induced by surfactants.
      • Paye M.
      • Cartiaux Y.
      • Goffin V.
      • Pierard G.E.
      Hand and forearm skin: comparison of their respective responsiveness to surfactants.
      Although inherent irritation potential (based on mildness of individual ingredients used) is a good starting point, a product containing ingredients with low irritation potential can still be defatting and, therefore, drying to the skin. Combinations of ingredients can also have different effects than individual ingredients. A test mimicking the actual use (ie, cleansing of skin) is thus important to define which products have the least negative impact on skin condition (Fig 3; Table 1). The FCAT testing shown in Fig 3 utilizes the visual assessment of skin cleansed with a variety of products to demonstrate the effect of surfactant systems on skin dryness. Within the test represented in Fig 3, sites washed with product code B were similar to those that were untreated and significantly less dry than other articles tested. Product code D was also significantly less drying than product codes A and C. The milder surfactant-based systems resulted in less drying of the skin over the test treatment of 18 washes.
      Figure thumbnail gr3
      Fig 3Comparison of skin dryness because of frequent handwashing using foamed soaps in a Forearm Controlled Application Test (FCAT). Forty-eight subjects used the products 18 times over 5 days. Each site utilized test product volumes of 0.2 mL on day 1 and 0.3 mL on days 2 to 5. Visual evaluation was done by trained panel. Study was conducted by Hill Top Research, Inc. (236 Osborne Street, Winnepeg, MB R3L 2W2) Study ID 04-123162-114.
      Table 1Visual evaluation scale for dryness
      GradeDryness
      0None
      1Patches of slight powderiness and occasional patches of small scales may be seen. Distribution generalized.
      2Generalized slight powderiness. Early cracking or occasional small lifting scales may be present.
      3Generalized moderate powderiness and/or heavy cracking and lifting scales.
      4Generalized heavy powderiness and/or heavy cracking and lifting scales.
      5Generalized high cracking and lifting scales. Powderiness may be present but not prominent. May see bleeding cracks.
      6Generalized severe cracking. Bleeding cracks may be present. Scales large, may be beginning to disappear.
      Scale adapted from HTR reference No. 04-123162-114, Hill Top Research, Inc.

      Skin-conditioning agents

      Skin-conditioning agents are important across a wide variety of product types and forms. The addition of skin-conditioning and -moisturizing agents to a formulation can have a significant impact on the overall drying potential of a product by either replacing or helping to prevent further loss of moisture and by refatting the skin.
      • Jones R.D.
      • Jampani H.B.
      • Newman J.L.
      • Lee A.S.
      Triclosan: a review of effectiveness and safety in health care settings.
      • Lauharanta J.
      • Ojajarvi J.
      • Sarna S.
      • Makela P.
      Prevention of dryness and eczema of the hands of hospital staff by emulsion cleansing instead of washing with soap.
      • Loden M.
      Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream.
      • Held E.
      • Agner T.
      Comparison between 2 test models in evaluating the effect of a moisturizer on irritated human skin.
      • Held E.
      • Lund H.
      • Agner T.
      Effect of different moisturizers on SLS-irritated human skin.
      There are different types of skin-conditioning agents, which are distinguished by their effects. Emollients (such as PEG-45 palm kernel glycerides or isopropyl myristate) smooth the skin surface and improve the appearance of skin by reducing flaking and improving pliability. Humectants (such as glycerin or methylpropanediol) increase moisture in the upper skin layers by binding water. Occlusive agents (such as mineral oil or dimethicone) retard the evaporation of water from the skin by forming a layer on the skin that moisture does not penetrate well. Other miscellaneous agents (such as behentrimonium methosulfate or polyquaternium-7) can enhance appearance by adhering to the skin surface. Different types of moisturizing agents make sense for different product application, and combinations of agents are usually best to maximize effectiveness. Skin-conditioning agents can also grant lubricity to cleansing products, improving the aesthetic appeal while washing and providing a soft after feel, once hands are rinsed and dried.
      In cleansing products, the use of mild surfactant combinations to ameliorate drying effects can be further enhanced by the addition of skin-conditioning agents. Although moisturizing agents have a great benefit, they cannot overcome the inherent binding or irritation potential of poor surfactant selection. Surfactants and moisturizing agents must work together to minimize the drying effects of washing with water. The combination of mild surfactants and appropriate skin-conditioning agents can result in products that exhibit minimal change to the skin moisture levels with frequent use. Figure 4 graphically represents the ability of mild surfactants (amphoacetate, isethionate, and sulfosuccinate) combined with moisturizing ingredients to improve the moisture levels seen in the skin when compared with washing with water alone. The FCAT testing and moisture meter assessment demonstrated that sites washed with the product containing sodium lauroamphoacetate as the main surfactant and sorbitol, polyquaternium-7, and PEG-45 palm kernel glycerides as emollients demonstrated a slight increase in moisture over the untreated site. Even in the cases in which the emollients utilized were similar (3 of the products tested utilized sorbitol as a moisturizing agent and 2 of the products utilized both sorbitol and polyquaternium-7 as emollients), it appears that it is the utilization of both mild surfactants and the proper skin-conditioning agents that makes the greatest difference to skin hydration. Only the product with a combination of a mild surfactant (sodium lauroamphoacetate) and multiple skin-conditioning agents demonstrated a positive effect (increase) on skin hydration in this test. All others varied in the level of moisture loss as compared with untreated skin. There were, however, significant differences in moisture content lost from the skin among the other products tested, depending on which surfactants were used and how much skin-conditioning agent(s) was present.
      Figure thumbnail gr4
      Fig 4Comparison of skin surface hydration change because of frequent washing using skin cleansers in a Forearm Controlled Application Test (FCAT). Forty-three subjects used the products (0.25 mL) 18 times over 5 days. Untreated skin utilized water alone for washing and rinsing. Moisture level was assessed utilizing a Skicon-200 (I.B.S. Co, Ltd., Shizuoka-ken, Japan) moisture meter. Clinical evaluation March 20, 2000, to March 24, 2000. Study ID 105098-70. Data on file.
      Skin-conditioning agents must be included in alcohol-based hand antiseptic product formulations, or alcohol will have a drying effect with repeated use. The trend toward increased use of alcohol products has been, in part, driven by the need to counteract the decreased compliance resulting from frequent handwashing with irritating and defatting skin cleansers.
      • Rotter M.L.
      • Koller W.
      • Neumann R.
      The influence of cosmetic additives on the acceptability of alcohol-based hand disinfectants.
      The benefit of this movement toward the use of these leave-on products, which do not require the use of water, could be offset by the drying effects of alcohol. Therefore, it is important to include skin-conditioning agents in alcohol-based products to increase and maintain compliance with recommended use patterns. The use of appropriate thickeners and emollients can also increase the antimicrobial efficacy of these products by increasing contact of the alcohol antimicrobial ingredient with microorganisms on the skin surface.

      White JH. US patent 5,288,486. Alcohol Based Antimicrobial Compositions. February 22, 1994.

      Figure 5 represents a modified FCAT test in which products were applied and left on the skin (instead of being rinsed off). The products tested all contain approximately the same concentration (61%-63% vol/vol) of alcohol, although the types of alcohol and the form (liquid, gel, or foam) varied. When hydration levels were measured, 2 of the products reduced the level of moisture in the skin over baseline 1 hour after application. Two of the 3 other products tested had a significant positive impact on the moisture level in the skin. All of the products demonstrated significant differences from baseline with the exception of product C. All of the products claim to be moisturizing. Because the alcohol levels were all very similar, it is obvious that other formulation excipients (including thickening and skin-conditioning agents) can demonstrate dramatic effects on the moisturization capabilities of alcohol-based hand hygiene agents. Testing on human skin and resultant data generated can make a substantial difference in the ability to evaluate claims made in regard to moisturization and thus allow informed decision making and a truly positive impact on moisture levels and skin condition.
      Figure thumbnail gr5
      Fig 5Comparison of moisture levels in skin 1 hour after single application of alcohol product in a modified Forearm Controlled Application Test (FCAT). Moisture level was assessed utilizing a Skicon-200 moisture meter with an MT-8C probe (I.B.S. Co, Ltd.) in 20 subjects. A single application of the test article (0.05 mL) was applied. One test site remained untreated. Triplicate readings were taken. Clinical evaluation June 3, 2004, to June 4, 2004. Study ID 04-123124-112. Data on file.
      Lotion products are an important part of any skin care regimen targeting good skin condition.
      • McCormick R.D.
      • Buchman T.L.
      • Maki D.G.
      Double-blind, randomized trial of scheduled use of a novel barrier cream and an oil-containing lotion for protecting the hands of health care workers.
      • Held E.
      • Sveinsdottir S.
      • Agner T.
      Effect of long-term use of moisturizer on skin hydration, barrier function and susceptibility to irritants.
      • DePaepe K.
      • Hachem J.P.
      • et al.
      Beneficial effects of a skin tolerance-tested moisturizing cream on the barrier function in experimentally elicited irritant and allergic contact dermatitis.
      • Ramsing D.W.
      • Agner T.
      Preventive and therapeutic effects of a moisturizer.
      Their function is the transfer of moisture to the skin surface. The routine use of lotions can help to maintain skin health through the replacement of moisture lost by washing or by soothing skin irritated by frequent glove use.
      • Highley D.R.
      • Savoyka V.O.
      • O'Neill J.J.
      • Ward J.B.
      A stereomicroscopic method for the determination of moisturizing efficacy in humans.
      • Marino C.
      • Cohen M.
      Washington State hospital survey 2000: gloves, handwashing agents, and moisturizers.
      Not all moisturizing agents work in the same way, and the same moisturizing ingredient in 2 different formulas may demonstrate less effectiveness in one than the other.
      • Rawlings A.V.
      Advances in dry skin stratum corneum biology and moisturization.
      It is therefore important to gather data that demonstrate the moisturizing efficacy of a product, rather than just an ingredient's presence in a formulation.
      A modified FCAT was conducted in which lotions were applied to the skin. The levels of hydration were measured 1 hour postapplication. Figure 6 demonstrated that the 3 different products containing glycerin had different moisturization efficacy profiles. One of the lotions demonstrated 35% better moisturization than the other 2 after 4 hours. The lotion that did not contain glycerin actually exhibited a negative number (loss of moisture) in the testing as compared with both initial values and the untreated control. Based on this information, it becomes clear how very important it is to evaluate a final formulation for skin effects and not to rely only on a listing of label ingredients when making product choices for use as part of an overall skin care regimen.
      Figure thumbnail gr6
      Fig 6Comparison of moisture levels in the skin after application of lotion products in a modified Forearm Controlled Application Test (FCAT). Moisture level was assessed utilizing a Skicon-200 (I.B.S. Co, Ltd.) moisture meter with an MT-8C probe in 20 subjects. Two applications of the test article (0.05 mL) were applied 30 minutes apart. Clinical evaluation August 18, 2004, to August 19, 2005. Study ID 04-12004-112. Data on file.

      Other ingredients

      There are a large number of other ingredients that can have an influence on user acceptance of a product. These include thickening agents, fragrance, color, and preservative. An ingredient's impact on aesthetic appeal of product is an important factor in ingredient selection. Inappropriately high fragrance levels or inclusion of an unacceptable fragrance can negatively impact use patterns, for example, as can a product that stains fabric or skin. A product must also be adequately preserved to be acceptable.

      Novel product forms

      When alcohol-based hand sanitizers were first introduced widely in the United States in the early 1980s as a replacement for handwashing, the drying effects of alcohol did little to encourage their use.
      • Centers for Disease Control and Prevention
      Guideline for hand hygiene in health-care settings: recommendations of the Health Care Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force.
      Currently, alcohol-based hand sanitizers intended exclusively for the health care market incorporate emollients and moisturizers in an effort to overcome this inherent drying effect.
      • Rotter M.L.
      • Koller W.
      • Neumann R.
      The influence of cosmetic additives on the acceptability of alcohol-based hand disinfectants.
      This has been successful to varying degrees and is extremely formula dependent. The use of alcohol-based products as a substitute for handwashing is appropriate in many cases because the hands of caregivers can often be contaminated with pathogens without being visibly soiled. In fact, the CDC guidelines suggest that, when used in this manner, these products help improve overall skin condition.
      • Centers for Disease Control and Prevention
      Guideline for hand hygiene in health-care settings: recommendations of the Health Care Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force.
      Because the intent behind the use of these products is (at least in part) to reduce the negative impact of handwashing, incorporation of moisturizing agents into these products is no longer optional. Newer formulations provide skin-conditioning agents that moisturize similarly to many hand lotions
      • Medvick J.
      • Klein D.
      • Greten Z.
      • Kaiser N.
      • Newman J.
      Novel characteristics of a 60% isopropanol hand rub formulated to meet tentative final monograph healthcare personnel handwash criteria.
      (Fig 7). Thus, the inclusion of appropriate skin-conditioning agents enables the use of alcohol-based hand sanitizers that provide both time savings and opportunity to reduce the frequency of washing with traditional cleansers and water.
      Figure thumbnail gr7
      Fig 7Comparison of moisture levels in the skin 1 hour after 2 applications of alcohol or lotion product in a modified Forearm Controlled Application Test (FCAT). Moisture level was assessed utilizing a Skicon-200 (I.B.S. Co, Ltd.) moisture meter in 20 subjects. Only the site for product B was significantly more moisturized than that of site for alcohol product (A) in pairwise comparisons. Clinical evaluation August 18, 2004, to August 19, 2005. Study ID 04-12004-112. Data on file.
      Figure 7 represents an evaluation and comparison of an alcohol product containing highly effective moisturizing agents to lotions in a modified FCAT study. Within this test, the alcohol product moisturized statistically as well as 2 lotions and statistically better than a third lotion. The alcohol product was directionally more moisturizing than all but 1 of the 4 lotions tested. It is possible to get great moisturization characteristics utilizing the proper ingredients, even in a product containing high levels of alcohol. It is false to assume that, because a product is a lotion, it is therefore moisturizing. Not all lotions, nor all alcohols, are moisturizing. Data to support the claims, in the form of data generated on human subjects, are necessary to prove value.
      Brushless surgical scrubs have become popular offerings because of formulations that help penetrate and can act on nail beds and cracks and crevices of the hand surface without brushes.
      • Jones R.D.
      • Jampani H.
      • Mulberry G.
      • Rizer R.L.
      Moisturizing alcohol hand gels for surgical hand preparation.
      Brush usage can result in physical damage, which is an additional insult to the dryness, irritation, and skin damage listed above. Although hand hygiene compliance in the surgical scrub area is not a major issue, other negative consequences of skin damage, such as barrier disruption and increased skin shedding, may be addressed through the use of this relatively new technology.
      Another important recent development is the advent of disposable pathway delivery systems that dispense foam soap. These systems utilize mechanical methods to induce foam, making the products more aesthetically pleasing to use. Although some formulations are based on the need to provide less expensive alternatives to liquid soap products, the more important opportunity exists in the ability to utilize milder surfactants that inherently do not foam well and to incorporate increased levels and improved combinations of skin-conditioning agents. In more conventional liquid soaps, these combinations could inhibit foam formation during washing. Thus, it is possible through the use of this foaming technology to formulate cleansing products that do not have a significant or measurable negative impact on skin condition. Figure 8 compares the differences in moisture levels in skin after human subjects washed multiple times over a 5-day period (FCAT study) with a variety of foamed soaps intended for use in the health care environment.
      Figure thumbnail gr8
      Fig 8Comparison of moisture loss because of frequent handwashing using foamed soaps in a Forearm Controlled Application Test (FCAT). Forty-eight subjects used the products 18 times over 5 days. Skin surface hydration level was assessed utilizing a Corneometer CM 820 (Courage-Khazaka, Kohl, Germany). Clinical evaluation February 2, 2004, to February 6, 2004. Study ID 04-12316-114. Data on file.
      Visual assessment of the skin (Fig 8) demonstrated that sites washed with product code B were similar to those that were untreated and significantly less dry than other articles tested. Product code D was also significantly less drying than product codes A and C. The milder surfactant-based systems resulted in less drying of the skin over the test treatment of 18 washes.
      At least 1 of the products (product code A), containing milder surfactants and significantly increased levels of skin-conditioning agents, demonstrated no negative impact on moisture levels in the skin as compared with the baseline levels of moisture present in the skin at study initiation. All other products tested, including 1 for which ingredients were unavailable, demonstrated statistically significant loss of moisture from the skin (as measured using a corneometer). Although all of the products tested are intended for use in cleansing hands, there are dramatic differences in the amount of moisture left in the skin after testing is completed.

      Conclusion

      The problem of sustaining compliance with hand hygiene practices is one that has been addressed from many different directions. Understanding how the condition of the health care worker's skin affects compliance and taking steps to improve skin health is an important angle that must not be overlooked. The CDC Guidelines for Hand Hygiene in Health Care Settings includes recommendations for improving skin condition and increasing compliance by using well-accepted products, with low irritancy potential, as part of infection control hand hygiene programs. It is possible to develop and select skin cleansers, alcohol handrubs, and lotions that work together to provide a positive impact on skin health and consequently help to sustain compliance with hand hygiene guidelines. Sophisticated formulation technologies and the proper selection of ingredients can provide new products and product forms. These technologies offer the opportunity to change the established paradigm that increased hand hygiene will result in increased skin damage and offer the promise of breaking the troublesome cycle of skin damage and reduced compliance.

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