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ONS Congress Safe Handling CE Symposia Links

Fri, 14 May 2010 15:16:09 GMT

Thank you for attending the satellite symposia "Putting Safe Handling of Hazardous Drugs Into Practice" held in conjunction with ONS Congress in San Diego, CA. on May 13, 2010.

For those of you who did not receive a copy of the handouts, please download them by clicking here.

You may complete the evaluation form by clicking here.

Please Note: Your CE Statement of Credit will be mailed to you in approximately 2-3 weeks. We ask that you check your demographic information to ensure accuracy when mailing out your statements of credit.

If you have any additional questions, please feel free to contact Laura De La Rosa at laura@asyntria.com or 832-426-2728.

Thank you,

STAT Educational Services

2010 Confirmation

Tue, 20 Apr 2010 16:48:39 GMT

Thank you once again for registering for tomorrow's Safe Handling Awareness Day webinar, provided by an educational grant from Carmel Pharma. IF YOU ARE PARTICIPATING IN A GROUP VIEWING: Each participant MUST pre-register in order to obtain CE credit. Webinar Links Below you will find the links that will grant you access to this webinar: April 20, 2010 1:00pm EST viewing: http://www.stratosfour.com/programs/kp.cfm?a=98&b=4263&c=0 April 20, 2010 3:00pm EST viewing: http://www.stratosfour.com/programs/kp.cfm?a=98&b=4264&c=0 Handouts Please click on the following link to download copies of the presentation for each of your attendees. www.statce.com/shad-2010 CE Credit Important: At the end of the program, the moderator will provide you with a link to the evaluation form that you will complete online. You will need to make sure this is done as soon as possible, to ensure that your credit is mailed to you in a timely manner. Anyone who does not complete the evaluation form within...

Safe Handling - Recommendations and Best Practices

Tue, 16 Mar 2010 15:19:24 GMT

Accreditation This knowledge-based program has been accredited for 1.0 contact hour of continuing education credit for pharmacists and pharmacy technicians. STAT Educational Services, a division of Asyntria, Inc., is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. ® This knowledge-based program has been accredited for 1.0 contact hour of continuing education credit for pharmacists and pharmacy technicians. This program has been approved by ASHRM toward fulfillment of the requirements of ASHRM designations of FASHRM (Fellow) and DFASHRM (Distinguished Fellow) and towards CPHRM renewal. The University of Nebraska Medical Center College of Nursing Continuing Nursing Education is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. This activity is provided for 1.25 contact...

An Overview of Swine Influenza A (H1N1)

Tue, 28 Apr 2009 20:19:42 GMT

To take this FREE CPE program, click here Learning Objectives At the conclusion of this program, participants should be able to: 1. Define and describe swine influenza A (H1N1) 2. List the signs and symptoms of swine influenza A (H1N1) 3. Outline the pharmaceutical treatment recommendations for confirmed and suspect ill cases of swine influenza A (H1N1) 4. Outline information to provide and/or discuss with patients regarding swine influenza A (H1N1) Program Details ACPE 384-000-09-004-H01P 1.0 Contact Hour Release date: 04-28-09 Expiration date: 04-28-12 Cost FREE Target Audience Pharmacists & Certified Pharmacy Technicians (Technicians should take this program at www.pharmacytechnician.org)

Tue, 21 Apr 2009 16:11:05 GMT

Register is closed for the LIVE Safe Handling Awareness Day CE Webinar, however an archived version of this program is now available on-demand...just click on CE Courses...choose your profession...and select Safe Handling: Recommendations & Best Practices This program is accredited for 1.0 contact hours of CE for pharmacists and healthcare risk managers; 1.25 contact hours for nurses. For more details on the program, click here In preparation for the program, please note the following: To obtain CE credit, participants will need to complete and submit an official CE Evaluation Form. Please download a copy of this form at http://www.statce.com/attachments/files/13/SHAD%20Eval09.pdf. Forms should be faxed to 1-888-247-8706 following the presentation. We strongly encourage that you test your computer system for technical compatibility prior to joining the program by visiting...

Webinar Tech Support

Tue, 21 Apr 2009 15:54:56 GMT

To test your system beforehand to make sure it meets the below requirements - click here.

Minimum System Requirements & Plugin Downloads

PC with Microsoft Windows OS
Internet Explorer (IE) 6.0 or higher (Download Here)
Windows Media Player 7.0 or higher (Download Here)
Sound card and speakers
Internet connection (Broadband recommended)
MS Word or Adobe Acrobat Reader (Download Here)

Webinar FAQs/Tech Support - click here

Safe Handling CE Resources

Tue, 17 Mar 2009 22:04:19 GMT

Webinar FAQs

Thu, 19 Feb 2009 21:40:48 GMT

A webcast, otherwise known as a webinar, is an audio and/or video event broadcast over the Internet. All you need is a computer with Internet access, speakers and the free Windows Media player to see and hear the program. There is no need for additional software. It's that simple. For the StatCE Webinar you will be provided with a link from which to participate. About 10-15 minutes prior to the start of the webinar, simply click on the link provided and fill out the necessary information on the registration page. After submitting your registration a new window will pop-up containing the webinar. The course will be fully contained within the new Window. There is no need for dialing in on the telephone. Be certain your computer speakers are turned up, sit back and enjoy the presentation. To ask a question during the webinar, you can click on the Feedback button along the lower part of the page. A chat window will come up. From here simply type your question in the box provided...

Jobs

Wed, 06 Feb 2008 19:32:36 GMT

Coming Soon.

Links

Tue, 05 Feb 2008 21:17:22 GMT

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CE Evaluation

noemail@statce.com — Wed, 02 May 2007 00:00:00 GMT

Objectives:

Release Date: 1-May-07 7:00 PM
Expiration Date: 30-Jul-07 7:00 PM

NTI CE Evaluation

noemail@statce.com — Tue, 01 May 2007 15:00:00 GMT

Objectives: This survey allows us to evaluate, and better improve, the effectiveness of our continuing education programs.

Release Date: 1-May-07 10:00 AM
Expiration Date: 1-May-10 10:00 AM
Please answer each question.

Program Evaluation 07-006

noemail@statce.com — Mon, 23 Apr 2007 20:00:00 GMT

Objectives:

The goal of this program was to provide current information regarding USP <797> regulations, the NIOSH High Risk Drug Alert and implications for compliance decisions. This program was designed to educate healthcare professionals on the proper handling of hazardous drugs.

Release Date: 23-Apr-07 3:00 PM
Expiration Date: 23-Apr-09 3:00 PM
Please answer the following questions to evaluate this program and provide us with your feedback.

Chemotherapy Safety Guidelines: Why We Need Them

2010-05-28T13:00:00Z

Instructor: Kerry Mahar, RN, MSN, AOCN

Background The risks of exposure to hazardous drugs have been documented for over 4 decades. Guidelines to protect patients, staff and the environment have been in place for more than 25 years. Despite the fact that this information has been incorporated into numerous versions of guidelines and institutional policies and procedures, there still remains incomplete understanding of risk and inconsistent application of the standards. Introduction Since the 1970’s it has been reported that the very agents used in the treatment of cancer can incur unwanted effects on those preparing and administering them. In particular, a study in Finland revealed that nurses who handled chemotherapy had that agent in their urine. (Falck, 1979) Subsequent reports revealed nurse complaining of many of the symptoms their patients, who had received full doses, experienced. These symptoms included nausea, vomiting, hair loss and mouth sores. Through the 1980’s and 1990’s numerous studies have confirmed the genotoxic effect on nurses and pharmacists exposed to antineoplastic agents (National Institute for Occupational Safety and Health, NIOSH, 2004). Fetal loss, abnormalities, and low birthweight have been related to length of maternal exposure (Hemminki, 1985). The risk of cancer in nurses who have handled chemotherapy was reported from leukemia data collected among Danish oncology nurses between 1943 and 1987. In addition, there seemed to be a relationship between leukemia rates and physicians working in the same department at that time. (Skov, 1992) The 2004 NIOSH Alert cites several examples of healthcare provider symptoms and injuries related to direct exposure. Skin contact and fume inhalation of carmustine led to severe GI distress in a nurse a few hours after exposure. Another nurse appeared to have developed allergic asthma after 3 years of work-related exposure to hazardous drugs. Lastly, a nurse’s aide, who had worn personal protective equipment (PPE) while handling urinals of patients who had received chemotherapy, developed skin irritation and a rash. The term hazardous drug was first used by the American Society of Health-System Pharmacists (ASHP) in 1990. A hazardous drug is defined as any chemical that is a physical hazard or health hazard. A physical hazard relates to combustibility or reactivity (i.e. solvents, some cleaning agents, etc.). A health hazard, the focus of this report, is a chemical that has shown to incur acute or chronic health effects in exposed individuals. (NIOSH, 2004.) Hazardous drugs are identified by having one or a combination of the following characteristics: genotoxic, teratogenic, carcinogenic, which cause fertility changes and result in organ toxicities even at low levels of exposure. (NIOSH, 2004) The International Agency for Research on Cancer (IARC) has identified numerous agents as either carcinogenic, probable carcinogenic and possible carcinogenic to humans. Alkylatings agents including cyclophosphamide and melphalan are some of the most carcinogenic agents. Other established carcinogens include arsenic trioxide, tamoxifen and thiotepa. Probable carcinogens include azacitadine, cisplatin, carmustine, etoposide and doxorubicin. Examples of possible carcinogens are dacarbazine, bleomycin and daunorubicin. Opportunity for Exposure The risk of a healthcare worker’s exposure to hazardous drugs (HDs) begins from the time a delivery arrives at the loading dock to the time the IV materials, syringes, and related safety equipment are discarded in the hazardous waste receptacle. The highest risk is related to the amount of drug one can be potentially exposed to and the amount of time one is open to exposure. Therefore, the highest rates of exposure are related to preparation and administration of antineoplastic agents. Exposure to HDs most often occurs from ingestion or inhalation of aerosolized prepared medication, dust or powder (pure drug or dried prepared medication), and less commonly accidental injection. Other mechanisms of exposure include contact with contaminated surfaces, and improper disposal or spill management. It is important to consider that improper handling at any point can lead to exposure to those who are unaware of the exposure at all. Preparation of antineoplastic agents involves the reconstitution and withdrawal of drug from vials, and transferring the drug to a syringe or IV bag. Administration involves connecting (and disconnecting) syringes or IV tubing to patient IV access. Any of these activities can result in an accidental spill or splash, splattering, spraying or aerosolization. Once an agent is outside of a closed system (aerosolized, spray, etc.) it can be ingested or inhaled or come into contact with skin or mucous membranes. Once ingested, inhaled or in contact with membranes, absorption can and does occur. Less obvious, and many may argue, far more prevalent, is contact and repeated exposure to minute amounts of drug in the treatment area. Such surfaces include desks and tables where chemotherapy may briefly be placed, keyboards used with gloved hands that handled a syringe or bag, patient treatment chairs, bedside tables, urinals and bed pans that have contained waste that may have excreted drug in it. After an individual exposure, measures must be taken to remove any product from skin, clothing and the immediate environment. Material Safety Data Sheets (MSDS) should be available to allow the best management of an exposure and the subsequent cleanup. Personal management usually involves removal of contaminated clothing and washing with soap and water. Mucosal contact must be dealt with immediately. Eye rinsing or use of an eyewash station is necessary for even the slightest exposure to the face. If ingestion occurs, it is not recommended that vomiting be induced. Emergency treatment should be sought immediately. Unfortunately, any drug that is absorbed by ingestion, inhalation or mucosal exposure cannot be removed. The amount of agent absorbed will most likely be very small, but the individual must be prepared to experience some type of effect (either local or systemic). In general there are no defined safe limits of exposure to hazardous drugs, according to NIOSH, the Occupational Safety and Health Administration (OSHA) or the American Conference of Government Industrial Hygienists (ACGIH). Guidelines In 1986, OSHA published guidelines for antineoplastic drugs. US Environmental Protection Agency (EPA) standards for the handling of hazardous waste have been in existence since 1976. OSHA (1999) and ASHP (1990) recommend hazardous drug waste be handled in the same fashion. Hazardous drug waste includes partially filled vials, undispensed products, unused IVs, needles and syringes, gloves gowns, underpads, contaminated materials from spill cleanups, and containers such as IV bags or drug vials that contain more than trace amounts of hazardous drugs and are not contaminated by blood or other potentially infectious waste. In 1998, the Department of Labor established the following hierarchy of hazard controls. Eliminate the hazard – not necessarily achievable as the drugs need to be prepared and administered Substitute – utilizing a less toxic substance Engineering controls – isolate the hazard by using equipment that is designed to protect from exposure Administrative controls – this includes educational and training standards, limiting personnel who come into contact with hazardous agents Personal Protective Equipment (PPE) – the individual’s use of the available barriers to protect oneself In 2004, NIOSH issued an alert identifying specific recommendations for the handling of antineoplastic agents. Keeping in mind the US Department of Labor’s hierarchy, the recommendations include practices related to: Receiving and Storage Drug Preparation and Administration Ventilated Cabinets Routine Cleaning Decontamination Housekeeping Waste Disposal Spill Control Additional guidelines that address hazardous drugs or the equipment in which they are manipulated have been developed by The Centers for Disease Control (CDC), National Institute of Health (NIH), International Society of Oncology Pharmacy Practitioners (ISOPP), ASHP, Oncology Nursing Society (ONS), United States Pharmacopeia (USP), and The National Sanitation Foundation. Profession-based guidelines like USP, ONS and ISOPP are all based on the recommendations of the 2004 NIOSH Alert. Each group has expanded on those practice areas pertinent to their roles. First and foremost, education and training that is required is outlined in all of these guidelines. Any worker who may be at risk of exposure to a hazardous drug must receive the appropriate amount of training to both perform the tasks correctly and to protect themselves. For instance, ISOPP, outlines the training required for anyone preparing or administering chemotherapy. In addition, the preparation of parenteral cytotoxic drugs should be undertaken only by pharmacy personnel. ONS guidelines address in detail the use of PPE during handling, administration and disposal of waste products. The following table summarizes the recommendations, components and implementation guidelines of the 2004 NIOSH Alert. Recommendation Components Guideline Implementation Assess the hazards of the workplace 1. Evaluate the workplace to identify and assess hazards before anyone begins work with hazardous drugs. Physical layout Equipment Decontamination process Potential points of exposure 2. Regularly review the current inventory of HDs, equipment, and practices Institutional Safety Committee 3. Conduct regular training reviews with all potentially exposed workers Include employees in discussions related to effectiveness or issues concerning the program Handle drugs safely 1. Implement a program for safely handling HDs at work and review this program annually on the basis of the evaluation Policies and Procedures for: labeling, storage, spill control 2. Establish procedures and provide training for handling HDs safely, cleaning up spills, and using all equipment and PPE properly Make spill kits and PPE available and easy to access. 3. Establish work practices related to both drug manipulation techniques an to general hygiene practices. Policy on food items in the work area. Use and maintain equipment properly 1. Develop workplace procedures for using and maintaining all equipment that functions to reduce exposure. Policy on use of ventilated cabinets, closed system transfer devices, closed IV systems, PPE The Resource Conservation and Recovery Act - commonly referred to as RCRA - is the primary law governing the disposal of solid and hazardous waste. Congress passed RCRA on October 21, 1976 to address the increasing problems the nation faced from our growing volume of municipal and industrial waste. RCRA, which amended the Solid Waste Disposal Act of 1965, set national goals for: Protecting human health and the environment from the potential hazards of waste disposal. Conserving energy and natural resources. Reducing the amount of waste generated. Ensuring that wastes are managed in an environmentally-sound manner. The following sections highlight the detailed recommendations for preparation, administration and disposal of chemotherapy. These guidelines were selected from the ISOPP Journal of Oncology Pharmacy, Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings Practice by the NIOSH and the 2009 Oncology Nursing Forum. Preparation All cytotoxic medications should be prepared in a central location within a sterile environment. A Biologic Safety Cabinet (BSC) must be used for all reconstitution and preparation of cytotoxic medications for administration. Personal protective equipment (PPE) will include a non-linting and non-absorbent polyethylene gown with cuffs gripped at the wrist. Disposable sleeve covers may also be used to protect the wrist and lower arm. If in a cleanroom, hair covering, overshoes and surgical mask must be worn. Gloves should be powder-free and proven resistant to chemotherapy. Latex, nitrile and neoprene are the only materials validated for handling of chemotherapy. Double gloving is recommended and gloves should be changed after 30 minutes of use. The use of special devices to protect the handler, preparer and administrator of cytotoxics should be implemented. This includes a closed system transfer device that prevent spraying and aerosolization (ISOPP 2007). Use of a Closed System Transfer Device (CSTD) NIOSH defines a CSTD as a device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system (NIOSH 2004). ISOPP further states that the devices need to be leak proof and airtight. While there are numerous marketed devices currently, there is a paucity of published literature supporting their benefits. One of the early studies demonstrated the reduction of both surface contamination and urinary presence of chemotherapy six months after the implementation of a closed system transfer device. Another study evaluated five different marketed devices to determine if they met the NIOSH and ISOPP definitions of a CSTD. Following a two-part evaluation, only one of the devices was successful in meeting these definitions of a CSTD. Many hospitals are either currently using or evaluating the CSTD products on the market. It is recommended to undertake your own evaluation to ensure that it meets the NIOSH and ISOPP definitions and has peer-reviewed data to supports its claims. Administration (ONS 2009) It is recommended that a pharmacist attach and prime IV tubing to the cytotoxic agent to be administered. All chemotherapy should be labeled to indicate its hazardous nature. Storage of these agents should be in specified containers in a location that limits exposure (i. e. on a specific shelf in the medication preparation area). IV set up should be closed and all connections should be luer-locked. Utilization of closed system transfer devices is recommended. PPE will include a non-linting and non-absorbent polyethylene gown with cuffs gripped at the wrist. Gloves should be powder-free and proven resistant to chemotherapy. Double gloving is recommended. If there is a risk of splash, eye and face protection should be used. A respirator (such as a non-powered, air-purifying, particulate –filter respirator) should be worn when administering an aerosolized HD. PPE should be worn for administration of HDs by any route, spiking IV bags containing HDs and changing IV tubing, priming IV tubing, handling leakage from tubing, syringe and connections sites. PPE should also be worn when disposing of HDs and items contaminated by HDs. (ONS 2004) Dispose of the gown after each use or if it becomes soiled. Remove the gown and outer gloves and place into the hazardous waste receptacle. Then remove the second pair of gloves and dispose. (NIOSH, 2004) Wash hands with soap and water. Disposal of Waste (NIOSH 2004) Waste Disposal Trace waste (those that contain less than 3% of the original quantity of HD) which consists of used syringes, IV tubing, gowns, gloves, empty vials should be placed in a yellow chemotherapy waste container. Disposal of arsenic trioxide and any bulk amounts (3% original quantity) should be in an RCRA-rated container. Housekeeping Wear two pairs of gloves and a disposable gown when handling soiled linen, stool or urine from patients who have received HDs within the last 48 hours. Wear a face shield if a splash risk (NIOSH 2004). Linen may be placed in a leak-proof laundry bag for usual cleaning (ONS, 2009). Dispose of the gown after each use or if it becomes soiled. Remove the gown and outer gloves and place into the hazardous waste receptacle. Then remove the second pair of gloves and dispose. Wash hands with soap and water. Do not use a hand sanitizer (NIOSH 2004). Spill Management All institutions should have a specific policy and procedure for spill clean up. Spills and the clean up is considered high risk for aerosolization and splash. In addition to double gloving and gowning, face shield and respirator use is required (NIOSH 2004). Most recently, in 2009, ONS and the American Society of Clinical Oncologists (ASCO) developed a joint set of Chemotherapy Administration Standards. The joint ASCO/ONS guidelines are a unique and comprehensive approach to standardizing the entire process of chemotherapy treatment. Multidisciplinary standards were developed regarding the flow of chemotherapy administration: The review of clinical information and regimen selection Treatment planning and informed consent Order/prescription writing Drug Preparation Treatment compliance Administration and monitoring Response and toxicity monitoring There are eight standards. They include staffing, planning, practice, ordering, preparation, administration, patient consent and education, and monitoring/assessment (Jacobson et al., 2009). There is no specific standard related to safe handling but these standards speak to adequate training of personnel, education of patients and monitoring and re-assessment of the plan of care and response to treatment. Discussion The availability and specificity of the guidelines for safe handling of chemotherapy are undisputed. Unfortunately, there are many who do not have enough knowledge of the risks or of the guidelines which has resulted in less than optimal adherence to the recommendations. Barriers to adherence include lack of clear institutional policies, denial or dismissal of risks and inconvenience (Mahar, 2008). Raising the awareness of risks and how to protect oneself is one way to improve adherence. The establishment of practice-based organization position statements and creating a Safe Handling Awareness Day has certainly raised awareness, but has there been a change in practice? Increasingly, non-providers or indirect caregivers are also at risk of exposure. Oral chemotherapy is taken by the patient or administered by a family member. These therapies are also taken for extended periods of time, so that bottles and pills are more commonplace outside of the clinical area. Family, assistive personnel and pets can be exposed. As more agents are used in the clinical setting for non-oncology diseases (i.e. neurology, rheumatoid arthritis, organ transplant) clinicians who may not have the education and training that oncology nurses receive. Ensuring this group of clinicians receives that education and training is the responsibility of the employer. References American Society of Health-Systems Pharmacists. ASHP Guidelines on Handling Hazardous Drugs. 2006, 63:1172-1191. Cass, Yaakov and Setton, Isaac. 25 Years of Safe Handling of Cytotoxics (Antineoplastics) in Israel. Journal of Oncology Clincal Practice. 2006, Vol 12, pp. 83-90. Falck K., Grohn P, Sorsa M. et all Mutagenicity in Urnine of Nurses Handling Cytostatic Drugs. Lancet. 1979. 1:1250-1251. Gambrell, J and Moore, S. Assessing Workplace Compliance with Handling of Antineoplastic Agents. Clinical Journal of Oncology Nursing. 2006,Vol 10, No. 4. Pp 473 – 477. ISOPP, ISOPP Standards of Practice: Safe Handling of Cytotoxics, Journal of Oncology Pharmacy Practice (Suppl) Vol 13, pp. 1-81. Jacobson, J. O., Polovich, M., McFiff, K. K., LeFebvre, K. B., Cummings, C., Galioto, M., Bonelli, K. R., and McCorkle, M. R.. Ameirica Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administratin Safety Standards. Oncology Nursing Forum. Vol. 36, No. 6, Nov 2009. Martin, S. and Larson E. Chemotherapy Handling Practices of OUtpaitent and Office-Based Oncology Nurses. ONF, 2003, Vol 30, No. 4. Pp 575-581. Mahar K. Practical Applications: Overcoming Barriers to Chemotherapy Safety in Nursing. The Oncology Nurse. Vol. 1 No. 5, Oct/Nov 2008. (suppl). National Institute for Occupational Safety and Health. Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings. Sept 2004. Polovich, Martha. Safe Handling of Hazardous Drugs. Online Journal of Issues In Nursing. Sept 30, 2004. US Pharmacopeial Convention, USP 797. Guidebook to Pharmaceutical Compounding Sterile Preparations, 2008. United States Department of Labor, OSHA Technical Manual, Section 4, Chapter 2 Vanchieri, C., Health Hazards to Community Practice Nurses: The Big Worry, Community Oncology, 2005, May/June Vol 2,, No 2. Pp 277-279 Valanis, B. G, Vollmer W. M., Labuhn K. T, et al. Acute Symptoms Associated With Antineoplastic Drug Handling among Nurses. Cancer Nursing, 1993, 15:288-295. Martin S., The Adverse Health Effects of Occupational Exposure to Hazardous Drugs Community Oncology, 2005. 2: 397-400. Ritchie, MA, McAdams C, and Fritz, N. Exposure Risk in the Handling and Administration of Chemotherapy Agents: A Review and Synthesis of the Literature. Online Journal of Knowledge Synthesis in Nursing, 2000,Vol 7, No. 4

Regulations and Recommendations of Safe Handling

2010-04-26T13:00:00Z

Instructor: Stephen Eckel, PharmD, MHA, BCPS & Scott W. Savage, Pharm.D., M.S.

In 1917, mustard gas (CH2ClCH2)S was a feared chemical weapon that caused a myriad of symptoms frequently resulting in death. However, by the late 1920s a topical form of mustard gas showed promising effects alleviating pain associated with superficial tumors.(1) By 1946, nitrogen mustard (also known as chlormethine or mechlorthamine) , an agent once intended to end life, had become a pivotal agent in lymphoma cancer treatment. (2) Although surgery and radiation continue to be a mainstay in the cooperative efforts of the mulitdisplanary healthcare team to treat cancer, medicinal treatment options continue to expand available treatment modalities. With continued scientific advances, chemotherapy and biologic therapy is now commonly administered with curative intent, as adjuvant or neoadjuvant therapy, or palliative symptom relief in advanced disease.(3) In the United States, the American Cancer Society estimates almost 1.5 million new cancer cases and roughly 600,000 deaths from cancer in 2009.(4) The National Cancer Institute forecasts a doubling of this figure by 2050 with the growing and aging population.(5) With treatment not only is the patient at risk, but the health care professionals caring for the patient have a high risk of being exposed to these hazardous drugs. Considering this risk, coupled with growing patient volumes, it is paramount to have a clear understanding of the exposure risk, the national recommendations and standards related to hazardous drugs, and strategies to reduce exposure risk. Hazardous Drugs and Exposure Effects: Hazardous drugs are drugs that possess qualities presenting the risk of unwanted health effects to those handling these drugs. The term hazardous drug, first used within the American Society of Health-System Pharmacist (ASHP)’s “Technical Assistance Bulletin (TAB) on Handling Cytotoxic and Hazardous Drugs”, was further expanded in 2004 by the National Institute for Occupational Safety and Health (NIOSH).(6) In the NIOSH Alert, drugs considered hazardous are identified by exhibiting one of the following six criteria: carcinogenicity, teratogenicity or developmental toxicity, reproductive toxicity in humans, organ toxicities at low doses in humans or animals, genotoxicity, or new drugs that mimic existing hazardous drugs in structure or toxicity. (Table 1).(7,8) Health care workers are at an exposure risk throughout the medication use process, not only during the preparation, distribution, and administration phases, but also during the subsequent disposal process of the used hazardous drug. Potential routes of exposure include inhalation, dermal contact, ingestion, or injection. In fact, it is estimated that roughly 5.5 million U.S. health care workers, including physicians, nursing, pharmacy, environmental services, research, and shipping/receiving personnel, will be exposed to hazardous drugs annually at some point throughout the process.(7) Health hazards associated with hazardous drug exposure were initially reported in the 1970s, when patients were diagnosed with secondary malignancies post-treatment with hazardous drugs for their primary neoplasm. Additionally, historical laboratory data compiled by the International Agency for the Research of Cancer (IARC) supported these observations and lead to the classification of certain hazardous drugs as human carcinogens (Group1) and probable human carcinogens (Group 2A). (Table 2)(9,10) Falck et al., first reported occupational exposure to hazardous drugs. Nurses caring for patients receiving a cyclosphosphamide based regimen had higher mutagenic markers in their urine. The mutagencity measure was less remarkable after a “duty-free” weekend indicating potential correlation of exposure frequency to cumulative occupational exposure.(11) From a pharmacy perspective, personnel preparing hazardous drugs in a horizontal, laminar airflow work bench (LAFW) had detectable mutagenic markers. However, personnel using a vertical, biological safety cabinet (BSC) had non-detectable mutagenic markers.(12) Additional evidence has validated acute health effects associated with hazardous drug exposure in nursing and pharmacy personnel including hair loss, hypersensitivity, headaches, adverse reproductive effect, increased risk of neoplasm, and chromosomal abnormalities.(13-19) Table 1: NIOSH Alert Hazardous Drug Classification (7,8) Characteristic Result Carcinogenicity Causes cancer Teratogenicity Damages developing fetuses Reproductive toxicity Impairs fertility Organ toxicity Impairs organ function Genotoxicity Damages DNA Mimic existing hazardous drugs in structure and toxicity Any of the above Sources of Exposure: Exposure of health care professionals to hazardous drugs is varied in route as previously mentioned. Surface contamination is evident in all phases of the medication use process. During the preparation, administration and distribution phase, contamination has been documented within pharmacy and nursing areas.(20-22) Dermal contamination can be a direct result of the external contamination of hazardous drug vials which can subsequently lead to surface contamination of other areas. In 1999, six cancer treatment centers in Canada and the United States were evaluated for the level of contamination of hazardous drugs. Measurable amounts of contamination were detected in 75% of the pharmacy area samples and 65% of the administration area samples.(20) Additional studies have presented consistent results to other published data showing surface contamination within primary engineering controls (e.g. LAFWs, BSCs, compounding aseptic isolators, and cleanrooms), equipment used for preparation and administration of hazardous drugs (e.g. intravenous bags and tubing), and general work surfaces (e.g. desk, floors, countertops, and cabinets).(10,22-24) Such diverse contamination of work surfaces only increases the risk of personnel exposure. Measureable indicators of hazardous drug exposure in the urine of health care workers are documented in over 19 studies worldwide. A majority of these studies detected one or more hazardous constituent. Additionally of the 19 studies, four of them described secondary exposure to health care personnel that had no direct contact with the patient.(10) Based on the expected excretion of some of the measured hazardous drugs, in particular cyclophosphamide, inference was possible correlating an increased risk of cancer in those with systemic exposure.(20,25) Inhalation and ingestion exposure are also a potential risk. Although minimal data supports a complete understanding of the effects of these types of exposure, studies report little to no detectable contamination to significant contamination indicated by particulate air sampling. Ingestion serves as an alternative route to dermal absorption due to the combination of surface contamination transferring from the hands to the mouth.(10) This exposure data validated the incidence and risk of hazardous drug contamination and has garnered a response from governmental and health care professional bodies. These efforts, as detailed in the next section, all intend to reduce the occupational exposure risk of personnel. Safe Handling Guidelines and Standards: Guidelines to minimize exposure to hazardous drugs were first published by the Society of Hospital Pharmacists of Australia in 1981.(26) Today, there are multiple guidelines or references that guide the management of hazardous drugs.(7,27-31) Occupational Safety and Health Organization (OSHA) OSHA, whose mission is to assure safe and healthful working conditions for working men and women, first released guidelines for safe handling of hazardous drugs in 1986. Under OSHA standards, material safety data sheets (MSDS) for any hazardous drug must be available to the health care worker. Subsequent updates, reinforced prior findings that personnel exposure to hazardous drugs is an increasingly serious health concern promoting updated guidelines in 1995.(27,28) National Institute for Occupational Safety and Health (NIOSH) Although guidelines had been released from both governmental and professional organizations prior to 2004, data indicated that contamination and exposure to hazardous drugs within the workplace continued.(20-22) The NIOSH Alert, representing the recommendations of governmental and non-governmental thought leaders, intended to increase the awareness among the employers and the front-line health care workers. It applies to all workers who handle hazardous drugs and provides tools for preventing exposure that can be implemented by the employee or employer in their daily activities. ASHP Guidelines on Handling Hazardous Drugs Originally published in 1990, the updated guidelines intend to characterize the reoccurring and new concerns associated with the handling of hazardous drugs.(6) Additionally, it discusses specific recommendations concerning development of a safety program, general work practices, processes related to labeling and packaging, benefits of protective equipment, and containment and disposal of hazardous drugs.(29) American Society of Clinical Oncology (ASCO) and Oncology Nursing Society (ONS) The Oncology Nursing Society (ONS), originally established by nurses working in research settings involved with medical oncologist, released guidelines in 1982.(30) Updates to ONS’s guidelines, focuses on the knowledge base necessary to reduce risk associated with hazardous drugs including safe handling and administration.(31) Additionally, ASCO released guidelines intended for application at physician’s offices, infusion centers, free-standing cancer-centers, and any other treatment site, except a hospital outpatient department.(32) The updated ASCO guidelines include minimum level of services necessary to provide hazardous drug therapy.(33) Recently, ASCO and ONS jointly released standards encompassing seven domains of which preparation and administration practices are discussed. ASCO and ONS intend adoption should be the goal for best practice implementation in ambulatory care setting.(34) United States Pharmacopeia The Food, Drug, and Cosmetic Act of 1938 recognized the United States Pharmacopeia-National Formulary (USP-NF) as the official compendia of drug standards with the Food and Drug Administration (FDA) responsible for enforcement. USP Chapter <797>, based on its chapter number, is considered an enforceable regulation; however, the FDA looks to individual states to regulate pharmacy practice.(35,36) Within the most recent version, hazardous drugs as compounded sterile preparations has a distinct section with specific details related to the engineering and facility controls along with personnel training and attire required to prevent injury and illness associated with hazardous drug exposure. United States Environmental Protection Agency (EPA) The discovery of pharmaceuticals in surface, ground, and drinking waters around the United States has been a direct way for the everyday citizen to have an awareness of the risk associated with hazardous drugs. Established in 1976, the Resource Conservation Recovery Act (RCRA), sought to address the disposal of hazardous chemicals. The list of regulated chemicals include a variety of commonly used hazardous drugs. Failure to comply with the RCRA regulations can result in potential EPA violations and associated monetary fines.(37) The Joint Commission Created in 1951, this accreditation body is the oldest and largest health care standard-setting and accrediting body in the United States. In order to earn and maintain, The Joint Commission’s approval, an organization must undergo on-site survey. Within the Hospital Accreditation requirement, Medication Management and Environment of Care standards related to hazardous drugs. These standards and associated Elements of Performance (EP) guide the management, disposal, and minimization of risk associated with hazardous drugs. Non-compliance with these standards can result in non-accreditation for an organization.(38) Strategies to Reduce Potential Exposure: Knowing that there is a potential for exposure in your workplace to chemotherapy products is not enough. It is important to develop strategies for reducing contamination for employees. Some recommendations are easy to achieve and many places already complete them. However, others will require time to develop, resources to purchase, and organizational approval to implement. Determining and classifying medications as hazardous – NIOSH recommends a written inventory of all hazardous medications that will be used to be developed(7). This list needs to also come with a process to keep it updated and active, as new medications are added to the formulary. While the IARC provides carcinogenicity classifications of hazardous medications (table 2), this information is not current with all of the existing medications in the workplace. This table provides a good start for an organization in determining classification for medications they use, it should not be an end of itself. Medications that need to be reviewed for hazardous includes biologics, oral cancer medications, and medications that are teratogenic (but not used for the treatment of cancer). Another required recommendation is to have MSDS sheets available to all employees who could come into contact with the medication. These provide needed information to employees. Table 2: International Agency for the Research of Cancer Hazardous Drug Classifications (9) Group 1: (Carcinogenic to Humans) Group 2: (Probably Carciongenic to Humans) Arsenic trioxide Azathioprine Chlorambucil Chlornaphazine Cyclophosphamide Myleran Melphalan Semustine Tamoxifen Thiotepa Terosulfan Mustarge-Oncovin-Procarbazine-Prednisone (MOPP) Etoposide-Cisplatin-Bleomycin Azacitidine BCNU CCNU Chlorozotocin Cisplatin Doxorubicin N-Ethyl-N-nitrosurea Etoposide Mechlorethamine N-Methyl-nitrosourea Procarbazine Teniposide Implement policies and procedures for handling chemotherapy – After the list is determined, explicit policies and procedures need to be developed surrounding the handling of these medications. Each employee that has the potential for interacting with the chemotherapy needs to be evaluated for risk potential. This evaluation should start all the way from the receipt of medications to the administration of them. It has been studied that the outside of chemotherapy vials have trace contamination on them(22). This develops through the manufacturing process and could pose a concern for those handling medications on the loading dock. Issues to be discussed revolve around whether they should handle these medications while wearing gloves and should chemotherapy be stored in a separate area so as to not contaminate other medications. After the medication is in the pharmacy, USP <797> recommends that the medications be stored in a negatively pressured room. Another overlooked employee group is housekeeping. Many times they will enter the pharmacy to clean and not take the appropriate steps to protect themselves. Training employees – all employees need to be educated about the concerns with handling chemotherapy products. This should be done at the point of orientation, but should not end there. Continual education should be implemented as a part of the culture of the workplace. Part of the training should include the various steps that the organization uses to protect the worker. Simple steps include double-gloving with chemotherapy-approved gloves, use of a lint-free gown, hair nets, masks, shoe protection, and when needed, an eye shield. Other required steps in the training are the utilization of the appropriate environmental controls: either a barrier isolator or a biological safety cabinet. These procedures should both be taught and explained to the employee, but also observed to ensure compliance. Environmental controls – NIOSH and USP 797 have recommendations on the appropriate environmental controls that need to be used in the pharmacy. These are established to protect both the product from microbial contamination and the employee from exposure to hazardous drugs. Many of the recommendations are associated with airflow, hood placements and selection, and filtration of the air. Monitoring chemotherapy contamination – USP <797> recommends that an organization undertakes a surface wipe study to detect contamination of chemotherapy every 6 months(35). This will allow you to monitor over time the level of chemotherapy on surfaces in order to determine if exposure levels increase or decrease. In addition, there is also a recommendation from NIOSH to undertake medical surveillance of your employees(7). Cleaning procedures – at the end of the shift or day, the organization needs to develop a plan for cleaning the work surfaces of both the preparation and the checking areas. One area to discuss is the use of a decontamination product as a part of this process. There is currently one marketed for use that uses sodium hypochlorite. This product would be used in addition to the routine sterilization that occurs. Handling chemotherapy spills – it is imperative that each location that prepares and administers hazardous medications to store a chemotherapy spill kit. Each employee working in those areas should be knowledgeable about location and how to use it in the event of a spill. Disposal of hazardous medications – this is an area that is receiving significant national attention. The RCRA regulation provides some direction on disposal of medications(37), but each organization needs to develop policies that provide for disposal of chemotherapy vials and for chemotherapy infusions. Use of a closed system transfer device (CSTD) – over the past few years, there has been a significant growth of technology in this area. NIOSH defies a device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system(7). ISOPP further states that the devices need to be leak proof and airtight(39). While there are numerous marketed devices currently, there is a paucity of published literature supporting their benefits. One of the early studies demonstrated the reduction of both surface contamination and urinary presence of chemotherapy six months after the implementation of a closed system transfer device(21). Another study evaluated five different marketed devices to determine if they met the NIOSH and ISOPP definitions of a CSTD(40). Following a two-part evaluation, only one of the devices was successful in meeting these definitions of a CSTD. Many hospitals are either currently using or evaluating the CSTD products on the market. It is recommended to undertake your own evaluation to ensure that it meets the NIOSH and ISOPP definitions and has peer-reviewed data to supports its claims. Conclusions: Chemotherapy and hazardous drug preparation is not without risk. While these medications have been demonstrated to be effective at treating cancer and other disorders, they also have side effects not only for the patient, but also for the healthcare worker. The most important issue is to be aware of the concerns and risks present with handling hazardous drugs. There are also many regulations and guidelines to assist in providing recommendations on how to protect healthcare workers from exposure to chemotherapy. Reviewing these statements and instituting a few processes have been demonstrated to reduce the exposure to hazardous drugs. Bibliography 1. Joensuu G. Systemic chemotherapy for cancer: from weapon to treatment. Lancet Oncol 2008;9:304. 2. Goodman LS, et al. Nitrogen mustard therapy. JAMA 1946;132:126-32. 3. Medina PJ and Fausel C. Cancer treatment and chemotherapy. In Dipiro JT, eds. Pharmacotherapy: A Pathophysiologic Approach , 7th ed. New York, 2008: 2085-119. 4. Jamel A, et al. Cancer statistics, 2009.CA Cancer J Clin 2009;59:225-49. 5. Edwards BK, et al. Annual report to the nation on the status of cancer, 1973-1999, feature implications of age and aging on U.S. cancer burden. Cancer 2002;94;2766-2792. 6. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-49. 7. National Institute for Occupational Safety and Health. NIOSH alert: preventing occupational exposure to anti-neoplastic and other hazardous drugs in health care settings. http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf (accessed 2010 Mar 9). 8. Power L and Jorgenson J. Safe handling of hazardous drugs: video training program. American Society of Health-System Pharmacists. Maryland, 2006. 9. International Agency for the Research of Cancer. IARC monographs database on carcinogenic risks to humans. http://monographs.iarc.fr/ENG/Classification/index.php (accessed 2010 March 9). 10. Connor TH and McDiarmid. Preventing occupational exposures to antineoplastic drugs in health care settings. CA Cancer J Clin 2006;56;354-365. 11. Falck K, et al. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1979;1:1250-1. 12. Anderson RW, et al. Risk of handling injectable antineoplastic agents. Am J Hosp Pharm 1982;39:1881-87. 13. Valanis BG et al. Acute symptoms associated with antineoplastic drug handling among nurses. Cancer Nurs 1993;16:288-95. 14. Dranistsaris G , et al. Are health care providers who work with cancer drugs at an increased risk for toxic events? A systemic review and meta-analysis of the literature. J Oncol Pharm Pract 2005;11:69-78. 15. Selevan SG, et al. A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med 1985;313:1173-78. 16. Valanis BG, et al. Association of antineoplastic drug handling with acute adverse effects in pharmacy personnel. Am J Hosp Pharmacy 1993;50:455-62. 17. Skov T, et al. Leukaemia and reproductive outcome among nurses handling antineoplastic drugs. Lancet 1990;336:1446. 18. Sessink PJM, et al. Drugs hazardous to healthcare workers, a review article. Drug safety 1999;20(4);347-59. 19. Sessink PJM, et al. Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral blood lymphocytes after occupational exposure to antineoplastic agents. Mutation research 1994;309:193-99. 20. Connor TH, et al. Surface contamination with antineoplastics agents in six cancer treatment centers in Canada and the United States. Am J Health-Syst Pharm 1999;56:1427-32/ 21. Wick C, et al. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health-Syst Pharm 2003;60:2314-20. 22. Connor TH, et al. Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies. Am J Health-Syst Pharm. 2005;62:475-84. 23. Harrison BR, et al. Comparison of surface contamination with cyclophosphamide and flurouracil using a closed-system transfer device versus standard preparation techniques. Am J Health-Syst Pharm. 2006;63:1736-44. 24. McDevitt JJ, et al. Exposure of hospital pharmacists and nurses to antineoplastic agents. J Occup Med. 1993;35:57-60. 25. Bos RP and Sessink PJM. Biomonitoring of occupational exposure to cytotoxic anticancer drugs. Reviews on environmental health. 1997;12(1):43-58. 26. Harrison BR. Developing guidelines for working with antineoplastic drugs. Am J Hosp Pharm. 1981;38:1881-87. 27. United States Department of Labor, Occupational Safety and Health Administration. Hazard Communication. 29 CFR Part 1910.1200. http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=10099 (accessed 2010 March 10). 28. United States Department of Labor, Occupational Safety and Health Administration. Controlling occupational exposure to hazardous drugs. OSHA technical manual, TED 01-00-15. Section VI. Chapter 2. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html (accessed 2010 March 11). 29. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health Syst Pharm. 2006;63:1172-93. 30. Oncology Nursing Society: Outcome standards for cancer nursing education. Pittsburgh, 1982. 31. Polovich M, et al. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 3rd edition. Pittsburgh, 2009. 32. American Society of Clinical Oncology: Criteria for facilities and personnel for the administration of parenteral systemic antineoplastic therapy. J Clin Oncol. 1997;15:3416-17. 33. American Society of Clinical Oncology: Criteria for facilities and personnel for the administration of parenteral systemic antineoplastic therapy. J Clin Oncol. 2004;22:4613-15. 34. Jacobson JO, et al. American society of clinical oncology/oncology nursing society chemotherapy administration safety standards. 2009;99:1-7. 35. USP General Chapter <797>. The current United States Pharmacopeia and the National Formulary and Supplements. Rockville, Md: The United States Pharmacopeial Convention, 2007. 36. US Food and Drug Administration. Compliance Policy Guides Manual; CPG Sec. 460.200 Pharmacy Compounding. http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074398.htm (accessed 2010 March 11). 37. US Environmental Protection Agency. Hazardous Waste Regulations. http://www.epa.gov/epawaste/laws-regs/regs-haz.htm (accessed 2010 March 12). 38. The Joint Commission E-dition. Hospital Accreditation Requirements. http://amp.jcrinc.com/Frame.aspx (accessed 2010 March 12). 39. Special devices. J Oncol Pharm Pract.2007;13:27-30. 40. Jorgenson JA, Spivey SM, Au C, et al. Contamination Comparison of Transfer Devices Intended for Handling Hazardous Drugs Hosp Pharm—2008;43:723–727

Looking at the Safe Handling of Drugs a Whole New Way

2009-12-08T17:30:00Z

Instructor: Byron Peters B.S. Pharm., R.Ph., E. Thomas Carey, Pharm D

Risky Business: Understanding & Preventing Hazardous Drug Exposure

2009-11-13T14:00:00Z

Instructor:

Risky Business: Understanding & Preventing Hazardous Drug Exposure

2009-11-13T12:00:00Z

Instructor:

An Overview of Swine Influenza A (H1N1)

2009-04-28T13:00:00Z

Instructor: Wendy Meigs RPh/ Mike Johnston, CPhT/

Important Note: The development of this continuing pharmacy education program was expedited with approval of the Accreditation Council on Pharmacy Education (ACPE) in response to a nationally declared public health emergency by the US Department of Health and Human Services (HHS). This program was developed with the latest information available as of April 26, 2009, but since this topic is undergoing constant updates and revisions by the CDC and HHS, some information provided could possibly be outdated or revised. We strongly recommend that you obtain the latest information available directly from the CDC or HHS in addition to, and as a verification of, the information presented. The majority of this program utilizes content developed and originally published by the CDC, with permission. INTRODUCTION Swine Influenza A (H1NI), known as swine flu, is a respiratory disease of pigs caused by type A influenza viruses that causes regular outbreaks in pigs. Over the years, different strains of swine flu viruses have emerged. At this time, there are four main influenza type A virus subtypes that have been isolated in pigs: H1N1, H1N2, H3N2, and H3N1. However, most of the recently isolated influenza viruses from pigs have been H1N1 viruses.U.S. cases of human infection with swine influenza A (H1N1) viruses were first reported in Southern California and near San Antonio, Texas, in late March 2009. The Centers for Disease Control and Prevention (CDC) has determined that swine influenza A (H1N1) is contagious, but is unsure how easily the virus spreads between people. Like seasonal flu, swine flu in humans can vary in severity from mild to severe. According to the CDC, 12 human cases of swine flu were detected in the U.S. with no deaths occurring between 2005 and January 2009. Swine flu infection, however, can be serious and even fatal. In September 1988, a previously healthy 32-year-old pregnant woman in Wisconsin was hospitalized for pneumonia after being infected with swine flu and died 8 days later. A swine flu outbreak in Fort Dix, New Jersey occurred in 1976 that caused more than 200 cases with serious illness in several people and one death.Certain groups might be more likely to develop a severe illness from swine flu infection, such as persons with chronic medical conditions. Additionally, bacterial infections may occur at the same time as or after infection with influenza viruses and lead to pneumonias, ear infections, or sinus infections. SWINE INFLUENZA A (H1N1) Human cases of swine influenza A (H1N1) virus infection have been identified in several states, as well as in other countries. This is a novel influenza A virus that has not been previously identified in humans, and human-to-human transmission of the virus appears to be ongoing. Unlike the experience in Mexico, the United States is currently observing a less severe clinical spectrum of disease with infection by the identical virus strain. As of April 26, 2009, of the confirmed cases of swine influenza A (H1N1) virus infection, only two confirmed case-patients were hospitalized and there had been no reported fatalities in the United States. Mexican health officials have reported several hundred suspect cases, including several deaths associated with confirmed swine influenza A (H1N1) virus infection. In Mexico, many patients have experienced rapidly progressive pneumonia, respiratory failure requiring mechanical ventilation and acute respiratory distress syndrome (ARDS). Therefore, the impact of this virus on the two countries has been strikingly different to date. Novel influenza A virus infections in humans, including swine influenza A (H1N1) virus, represent a pandemic threat. Recognizing the historical precedent for the emergence of a pandemic influenza virus, which could have waves of disease with different morbidity and mortality and epidemiologic profiles, public health departments in the United States must remain vigilant. Swine influenza A (H1N1) virus is thought to spread in the same way as seasonal influenza. The virus is spread mainly from person to person through coughing or sneezing of infected individuals, however some people may become infected by touching a contaminated object and then touching their mouth or nose. Infected individuals may be able to infect others as early as 24 hours prior to the onset of symptoms and up to 7 or more days after becoming infected. SIGNS & SYMPTOMS The symptoms of swine flu in people are similar to the symptoms of regular human influenza and include: ·Fever · Cough · sore throat · body aches · headache · chills ·fatigue · diarrhea · vomiting DIAGNOSIS Official diagnosis of swine influenza A infection requires a respiratory specimen, collected while the infected person is still shedding virus, typically within the first 4 to 5 days of illness. Some individuals, especially children, may shed virus for 10 days or longer. Identification as a swine flu influenza A virus requires sending the specimen to CDC for laboratory testing. The infectious period for a confirmed case of swine influenza A (H1N1) virus infection is defined as 1 day prior to the case's illness onset to 7 days after onset. SWINE INFLUENZA A (H1N1) VIRUS DEFINITIONS A confirmed case of swine influenza A (H1N1) virus infection is defined as an individual with an acute febrile respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests: · real-time RT-PCR · viral culture A probable case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness who is: · positive for influenza A, but negative for H1 and H3 by influenza RT-PCR, or · positive for influenza A by an influenza rapid test or an influenza immunofluorescence assay (IFA) plus meets criteria for a suspected case A suspected case of swine influenza A (H1N1) virus infection is defined as an individual with acute febrile respiratory illness with onset: · within 7 days of close contact with a person who is a confirmed case of swine influenza A (H1N1) virus infection, or · within 7 days of travel to community either within the United States or internationally where there are one or more confirmed swine influenza A(H1N1) cases, or · resides in a community where there are one or more confirmed swine influenza cases. Close contact is defined as within about 6 feet of an ill person who is a confirmed or suspected case of swine influenza A (H1N1) virus infection during the case's infectious period. VACCINATIONS There is no vaccine currently indicated for swine influenza in humans. The seasonal influenza vaccine will likely help provide partial protection against swine H3N2, but not swine H1N1 viruses.The H1N1 swine flu viruses are antigenically different from human H1N1 viruses and, therefore, vaccines for human seasonal flu would not provide protection from H1N1 swine flu viruses. PHARMACEUTICAL TREATMENT There are four different antiviral drugs that are licensed for use in the US for the treatment of influenza: amantadine (Symmetrel), rimantadine (Flumadine), oseltamivir (Tamiflu) and zanamivir (Relenza). While most swine influenza viruses have been susceptible to all four drugs, the most recent swine influenza viruses isolated from humans are resistant to amantadine and rimantadine. At this time, CDC recommends the use of oseltamivir or zanamivir for the treatment and/or prevention of infection with swine influenza viruses. Suspected Cases Empiric antiviral treatment is recommended for any ill person suspected to have swine influenza A (H1N1) virus infection. Antiviral treatment with either zanamivir alone or with a combination of oseltamivir and eitheramantadine or rimantadine should be initiated as soon as possible after the onset of symptoms. Recommended duration of treatment is five days. Recommendations for use of antivirals may change as data on antiviral susceptibilities become available. Antiviral doses and schedules recommended for treatment of swine influenza A (H1N1) virus infection are the same as those recommended for seasonal influenza. (Table 1) http://www.cdc.gov/flu/professionals/antivirals/dosagetable.htm#table Confirmed Cases For antiviral treatment of a confirmed case of swine influenza A (H1N1) virus infection, either oseltamivir or zanamivir may be administered. Recommended duration of treatment is five days. These same antivirals should be considered for treatment of cases that test positive for influenza A but test negative for seasonal influenza viruses H3 and H1 by PCR. Special Considerations for Pregnant Women Oseltamivir, zanamivir, amantadine, and rimantadine are all Pregnancy Category C medications, indicating that no clinical studies have been conducted to assess the safety of these medications for pregnant women. Only two cases of amantadine use for severe influenza illness during the third trimester have been reported. However, both amantadine and rimantadine have been demonstrated in animal studies to be teratogenic and embryotoxic when administered at substantially high doses. Because of the unknown effects of influenza antiviral drugs on pregnant women and their fetuses, these four drugs should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus; the manufacturers'' package inserts should be consulted. However, no adverse effects have been reported among women who received oseltamivir or zanamivir during pregnancy or among infants born to such women. Special Considerations for Children Aspirin or aspirin-containing products (e.g. bismuth subsalicylate Pepto Bismol) should not be administered to any confirmed or suspected ill case of swine influenza A (H1N1) virus infection aged 18 years old and younger due to the risk of Reye syndrome. For relief of fever, other anti-pyretic medications such as acetaminophen or non-steroidal anti-inflammatory drugs should be recommended. ANTIVIRA CHEMOPROPHYLAXIS For antiviral chemoprophylaxis (pre-exposure or post-exposure) of swine influenza A (H1N1) virus infection, either oseltamivir or zanamivir are recommended. Duration of antiviral chemoprophylaxis is 7 days after the last known exposure to an ill confirmed case of swine influenza A (H1N1) virus infection. PATIENT CONSULTATIONS Pharmacy technicians should refer any patient considered a suspected case or describing any of the previously mentioned signs and symptoms to the pharmacist for consultation. According to CDC recommendations, pharmacists should consult confirmed cases to stay home and avoid contact with other people as much as possible to keep from spreading your illness to others. Suspect cases should be advised to contact their physician to report illness, by telephone or other remote means, before seeking care at a clinic, physician's office, or hospital, with the following exceptions for when immediate medical attention required. Immediate Medical Attention Required Persons who have difficulty breathing or shortness of breath or are believed to be severely ill should seek immediate medical attention Individuals who become ill and experience any of the following warning signs, seek emergency medical care. In children emergency warning signs that need urgent medical attention include: · Fast breathing or trouble breathing · Bluish skin color · Not drinking enough fluids · Not waking up or not interacting · Being so irritable that the child does not want to be held · Flu-like symptoms improve but then return with fever and worse cough · Fever with a rash In adults, emergency warning signs that need urgent medical attention include: · Difficulty breathing or shortness of breath · Pain or pressure in the chest or abdomen · Sudden dizziness · Confusion · Severe or persistent vomiting For More Information Pharmacy professionals or patients needing additional information should contact The Centers for Disease Control and Prevention (CDC) Hotline (1-800-CDC-INFO), which is available in English and Spanish, 24 hours a day, 7 days a week. References & Resources http://www.cdc.gov/swineflu/ http://www.hhs.gov/ http://www.who.int/csr/disease/swineflu/en/

Safe Handeling:Recommendations & Best Practices

2009-04-20T13:00:00Z

Instructor:

Overcoming Barriers to Chemotherapy Safety in Nursing

2008-07-31T13:00:00Z

Instructor: Kerry A. Mahar, RN, MSN, AOCN

Introduction The first reported risk to humans handling antineoplastics was published in 1979 by The Lancet medical journal, in a study that found mutagenic activity in the urine of nurses working in oncology units. (Falck, 1979) This finding led to the proposal that merely handling chemotherapeutic agents led to exposure and absorption. Some years later, Valanis and colleagues reported an association between the degree of skin contact or exposure and the presence of acute symptoms experienced by nurses. (Valanis, 1993) Inadvertent exposure to these drugs has serious health consequences; common acute symptoms include nausea, vomiting, headache, dizziness, hair loss, and liver damage. Furthermore, long-term effects have been uncovered, such as increased chromosomal alternations, hepatotoxicity, and abnormal reproductive outcomes. (Martin, 2005) Susan Martin, RN, of SUMART Healthcare Consulting, surveyed approximately 3700 members of the Oncology Nursing Society (ONS) who handled chemotherapy on a regular basis. Her survey revealed the occurrence of infertility, miscarriage, and pre-term labor and births among nurses who handled more than 9 doses of chemotherapy in a day. In addition, developmental issues among the children born to this group were noted, including Attention Deficit Hyperactivity Disorder (ADHD), speech delays, and learning disabilities. The National Institute for Occupational Safety and Health (NIOSH) defines recommended exposure limits (RELs) as concentrations of substances that are without adverse effect. Currently, there are no identified threshold limits for workplace exposure of hazardous drugs. According to the American Society of Health-System Pharmacists (ASHP), hazardous drugs include chemotherapy, hormones, anesthetic agents, and antiviral agents that have one or more of the following attributes: 1. Carcinogenicity 2. Teratogenicity or other developmental toxicity 3. Reproductive toxicity 4. Organ toxicity at low doses 5. Genotoxicity 6. Structure and toxicity profiles of new drugs that mimic existing drugs determined hazardous by the above criteria Despite the increasing awareness of known exposures and adverse outcomes, there continues to be resistance to the use of safe handling systems or their components. This resistance may be based on denial of risk, insufficient information, lack of enforcement of policy or regulation, or lack of provision of safe handling devices. An exploration of barriers such as these may be helpful in allaying some myths and misconceptions, and empower nurses to take more responsibility for their own safety and that of others. Risk of Exposure In general, the exposure risks for nurses are related to the preparation, transport, administration, disposal of chemotherapy waste and of bodily fluids. Except for needle sticks given by IM or SC route, accidental injection is much rarer due to the universal use of needle-free administrations. The highest risk of exposure for nurses is associated with preparation and administration, primarily through inhalation of aerosolized drug, direct contact (eyes, skin, mucosa), and ingestion of an improperly handled drug. In her 2008 article regarding the safe handling of hazardous drugs, Martha Polovich highlights the 1999 report by the Department of Commerce estimating that 5.5 million healthcare workers have the opportunity for exposure to hazardous drugs in the workplace. This estimate includes employees who directly purchase, store, prepare, deliver, administer, and discard chemotherapy, as well as those who risk exposure by working in the vicinity of the drugs. Certainly, a spill is the exposure risk one thinks of when needing/utilizing PPE and other safety devices as protection. However, unseen actual or potential small exposures should also be of concern. Even with needleless and some closed systems, the risk of exposure persists during attachment and detachment of connections. These releases of drug are miniscule, often inadvertent or unintentional, and can occur on a counter or at the patient's bed or chair. Because they go undetected, these small exposures put not only the administering nurse at risk, but also co-workers, patients, visitors, and others. Current Guidelines The Occupational Safety and Health Administration (OSHA) first published guidelines for safe handling in 1986. The following outlines the current NIOSH recommendations for Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings (NIOSH Publication No. 2004-165): 1. Assess the hazards in the workplace this includes the physical layout of the treatment/work area, volume of agents handled, spill response, and waste management. It also includes reviewing employee training on a regular basis. 2. Handle drugs safely this includes the establishment of safe handling practices, labeling, establishing training programs and establishing work practices related to both drug manipulation techniques and to general hygiene practices 3. Use and maintain equipment properly develop procedures for use and maintaining equipment The NIOSH recommendations also provide more detailed guidelines for appropriate use of PPE, receiving and storage of drug, drug preparation and administration, use and maintenance of ventilated cabinets, waste disposal, spill control, and medical surveillance. According to NIOSH, ...it is known that exposures to even very small concentrations of certain drugs may be hazardous for workers who handle them or work near them, and ...evidence indicates that workers may be exposed to hazardous drugs and are experiencing serious health effects despite current work practice guidelines. The use of CSTDs should be considered whenever available, as they limit the potential for generating aerosols and exposing preparers to needle sticks. NIOSH defines a CSTD as a device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system (NIOSH 2004). There are a variety of drug preparation and administration systems available today, however before using any products, it is important to make sure, as recommended by the International Society of Oncology Pharmacy Practitioners (ISOPP) and ASHP, that peer-reviewed, independent studies can be provided for each component of the system to validate it''s effectiveness. A device cannot be semi-closed. The PhaSeal® system is the only documented closed-system drug transfer device on the market. This system is designed to prevent leakage of drugs into the environment during preparation and administration (2005, Polovich M et al). The most current ONS guidelines (2003) are built upon OSHA and NIOSH recommendations. Specific guidelines regarding the preparation, administration by various routes, waste management, and handling of bodily fluids, spills, and accidental exposure are included. In particular, emphasis is placed on the use of closed system drug transfer devices (CSTDs and y-site administration sets) for IV administration and proper use of PPE. The ONS Chemotherapy and Biotherapy Guidelines and Recommendations for Practice, 2nd Edition, incorporates NIOSH 2004, OSHA 1999, and American Society of Hospital Pharmacists 1990 recommendations. These guidelines bring to light the need to properly utilize various components which, used properly, will provide the extent of protection intended to maximize the safety of the individual. No one device alone will ensure safety. In addition to the tangible components, the system must also include proper education and training. Persistent Barriers to Proper Handling Despite the fact that many institutions have created safety guidelines, some nurses continue to follow old or unsafe practices. Several studies have found a lack of standardization with regard to written procedures and guidelines, as well as significant inconsistencies in actual practices (Ritchie, et al). In these studies, the predominant practice was the use of gloves only. Most respondents reported they thought they were doing what was required. The Myth of It Can't Happen To Me Often, nurses who handled and administered chemotherapy before safe handling guidelines existed are those who fail to adequately follow the current guidelines. Gather a few of them together and common stories will abound: when they first began treating patients, they mixed and prepared chemotherapy in the medication room; they recall preparing doxorubicin for IVP by squirting drug to the tip of the needle (and beyond), resulting in visible red spots on counters, walls and ceilings; food and drinks were placed in the same area as these medications. Most will report that they have not been harmed by these practices, and some still feel these agents pose no or little danger given (1) whatever exposure there is, it is nothing compared to what the patient receives, or (2) the perceived lessened opportunity for exposure as chemotherapy is now prepared in the pharmacy, under a hood. Their contact with the bag, syringe, tubing, and subsequent waste is minimal in comparison to past practice. Mindset of Inconvenience As noted previously, actual physical contact with chemotherapy administration items (bag, syringe, tubing, and waste) is often brief. Consider the following: How long does it take to disconnect an IV set and put it in a waste container? That IVP vincristine only takes a few minutes, right? Changing the bag on a continuous infusion? The gown is bothersome to don, and hot and uncomfortable to wear. Inconvenience is an unfortunate way to look at PPE, but it is true that PPE takes time. The gowns in particular are cumbersome and make many users warm over time. Some nurses report that the use of the gown and face shield is disrespectful, or may give the patient the impression that they are toxic, making them feel more isolated or alienated than they already are. Lack of or Limited Access to Information To many nurses, especially in the acute care setting, new and updated policies and procedures are generated at record pace, making it difficult to stay abreast of current policy. From institution to institution, the method of introducing new policies and procedures can range from a general email to all nursing staff, handouts that highlight updates/changes, to one on one updates by a nurse educator. The use of chemotherapy in the non-oncology setting (RA, neurology, etc.) is increasing. The staff required to administer these medications may not be privy to the extensive resources available to designated oncology ambulatory clinics, and standard drug reference books do not address handling. Lack of Policies Chemotherapy is being administered in ever more diverse settings. IM methotrexate has been utilized in the homecare setting for years, and patients now receive both IV and oral chemotherapy in nursing homes and group residential homes (mentally ill or developmentally delayed clientele). In some settings, more so in non-academic sites, the lack of guidelines can cause non-adherence to NIOSH or ONS guidelines. Community sites, of course, can range from a small office with one nurse and no pharmacist to a franchise of practices under one umbrella with dedicated laboratory and a chemotherapy pharmacist available all day. Implementation of practice change can be a challenge, and PPE is a cost that is not necessarily recouped in the billing process. Noncompliance The enforcement or validation of competency related to these guidelines and policies is also a factor. Initial education and declaration of standards may have no follow up or review, and it is difficult to change a person's practice; often, nurses will receive and acknowledge the newer information but return to what they are accustomed to doing. This may be tied to awareness of risk, resistance to change due to the added burden additional tasks, or merely failing to recall the policy. Overall, the underlying theme of these factors is awareness, or more exactly, lack of awareness. Educational requirements for the establishment and maintenance of competency chemotherapy administration are as varied as patient care environments. In some cases, nurses administer chemotherapy with a bare minimum of education regarding the drugs. Nurses practicing outside the acute hospital setting are at higher risk of not getting at least the basic information required to safely administer chemotherapy and maintain their own personal protection. Finally, nurses who know the toxicities related to particular drugs do not always realize the risks to themselves or others in handling those agents. Overcoming the Barriers to Proper Handling Oncology nurses are one of the most well represented groups of specialty nurses in terms of identifying and addressing educational needs. The ONS provides live, electronic, and written forums for basic and continuing education on chemotherapy administration. The ONS Chemotherapy and Biotherapy Course provides an evidence-based foundation for the understanding of the toxicities and risks associated with the administration of antineoplastic agents. Proper preparation and administration techniques are reviewed and the substantiating guidelines are presented. This type of educational program, in tandem with institution-defined clinical orientation, is very often the basic structure of ensuring initial chemotherapy administration competency. Institutional Level Employers are not required to abide NIOSH guidelines, but are charged with establishing safe handling precautions. Organizations that provide care to patients that required the use of hazardous materials should - and often do - demonstrate that safety is an institutional value to which there is a commitment. Administrators need to prioritize implementation and compliance. The generation of policies and procedures should be paired with a comprehensive and realistic educational plan. Managers and supervisors must provide staff with the amount of time needed to review information or attend training. Training with regard to safe handling and disposal should also include data related to risks of exposure. Competency and compliance with policy and procedure should be evaluated on a regular basis, and remediation to ensure competency should be provided as needed. Interventions for non-adherence to policy should be communicated to all staff. The appropriate equipment for safe handling should be readily accessible. And at all times, staff should have ready access to the necessary guidelines/policies. The use of both environmental and biological monitoring may be utilized to increase awareness of risk as well as measure compliance with safe practice; NIOSH, ASHP and ONS recommend the use of biologic monitoring (urine testing) as part of a comprehensive safe handling system. Professional Level All personnel dealing with patients receiving chemotherapy have a stake in ensuring chemotherapy is administered safely. Unsafe chemotherapy preparation and administration poses exposure threat to others. Countertop contamination, aerosolization, spills and improper disposal can impact the patient, visitors, nursing aides, housekeepers, and other health providers. Therefore, adherence to safe handling procedure and embracing an institution's values is demonstrates respect for coworkers, patients, and community. Peer-to-peer demonstration and expectation of adherence to policy and procedure, including the use of proper equipment is important in maintaining the safety culture generated by an institution's commitment to patient and staff safety. The role of the preceptor is key to ensuring that new employees adopt the practices prescribed by the institution. Selection and preparation of preceptors is often the responsibility of the Nurse Manager and the Clinical Nurse Specialist or Clinical Educator, and a definitive preceptor preparation and selection process should include affirmation of competency, teaching skills, communication and feedback skills, and the proper utilization of resources. Individual Level Ultimately, all nurses are responsible for ensuring their own protection. Knowing the hazards and how to protect oneself is primary to practice. Individuals should have the proper resources (clinical support, policies and procedures, equipment, time) before preparing and administering chemotherapy. Despite the institution's definition of competency, each individual has his or her idea of what makes them competent to practice. Maintaining membership in groups such as ONS and a local chapter can help an individual connect with others who have similar practices and concerns about practice. Networking and sharing experiences can lead to questioning practice and empowering one to address concerns with others within their institution. Gambrell and Moore (2005) suggest using the SOLVE® 5 Step Problem-Solving Process (Action Services LLC, Rock Hill SC), which is very similar to the nursing process, to implement change in practice in the use of safe handling procedures. The SOLVE method relies on personnel to expose organizational procedures, tools, and training that empower personnel to act. This is a nonpunitive process that allows anyone within a system to look at problem and provide direct input. The involvement of those from all areas can lead to more open communication and comprehensive understanding of issues (pharmacy, nursing, materials management, etc.), and subsequently provide a better outcome with respect to increased use of safety equipment or safe handling practices. Summary No one knows what the safe limit of exposure to various carcinogenic or mutagenic agents might be. At this time, there is no device or test which can satisfactorily monitor the degree of exposure to cytotoxic drugs. The goals should be to minimize or remove the risk of exposure at every opportunity during the shipping, delivery, preparation, transport, administration, and disposal of chemotherapy. Establishing and maintaining competency around the safe handling and administration of chemotherapy is dependent on both the individual's understanding of the risks and the support of the organization. Decisions to practice safe handling of antineoplastic agents among nurses appear to be related to knowledge of risk of exposure and institutional guidelines (Ritchie, et al). It seems that in addition to the establishment of guidelines for safe handling, a mechanism for enforcement or evaluation is required for program effectiveness. Institutions must provide the tools for staff to perform their duties in the safest possible manner, and the staff must be willing to use these tools. As discussed, OSHA, NIOSH and ONS provide complete and detailed recommendations for the safe handling of chemotherapeutic agents. Employers refer to these guidelines to create policies and procedures for nurses, pharmacists, physicians, environmental services, etc. The creation, dissemination and enforcement of these policies are then delegated to managers, boards and committees, and many institutions incorporate members of these groups into other organizational bodies. Including nurses and pharmacists in the development of policies and procedures that affect their adoption is a key factor in the generation of a sensible policy that is feasible in practice. References Falck K, Grohn P. et al. (1979). Mutagenicity in urine of nurses handling cytostatic drugs. The Lancet. 1(8128):1250-1251. Gabrell, J. and Moore, S. Assessing Workplace Compliance With Handling of Antineoplastic Agents. Clinical Journal of Oncology Nursing Volume 10 Number 4 (2006), pp. 473-477. Martin, S. and Larson, E. Chemotherapy-Handling Practice of Outpatient and Office-Based Oncology Nurses. Oncology Nursing Forum Volume 30, Number 4, 2003. Martin, Susan. The adverse health effects of occupational exposure to hazardous drugs. Community Oncology, Sept/Oct 2005 pp. 397-400. NIOSH Publication No. 2004-165: Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings Oncology Nursing Society, Safe Handling of Cytotoxic Drugs. (2004 update of 1997 original) Polovich M. Safe Handling of Hazardous Drugs. 2008 American Nurses Association. The Online Journal of Issues in Nursing. ISSN: 1091-3734. Polovich M., Blecher CS, Glynn-Tucker EM, McDiarmid, M and Newton, SA. Safe handling of hazardous drugs. Pittsburgh PA: ONS; 2003. Ritchie, M. A., McAdams, C. and Fritz, N. Exposure Risk in the Handling and Administration of Chemotherapy Agents: A Review and Synthesis of the Literature. The Online Journal of Knowledge Synthesis for Nursing. Feb 2000, 7(4) Shaner-McRae, H. McRae, G. and Jas, V. The Online Journal of Issues in Nursing 2007; 12(2). Valanis, B. Vollmer, W. Labuhn, K, and Glass A. Acute symptoms associated with anitneoplastic drug handling among nurses. Cancer Nursing (1993) Volume 16: 288-295. Vanchieri, C. Health Hazard to Community Practice Nurses: The Big Worry' Community Oncology May/June 2005, 2(3) pp. 277 279.

The Basics of Safe Handling Hazardous Drugs

2008-07-11T13:00:00Z

Instructor: Timothy Tyler, PharmD

The safe handling of hazardous drugs is a subject that is as relevant today to the medical oncology community as it was when the dialogue sprouted in the literature three decades back. There is little else that has the potential to so dramatically impact not only the work lives but downstream health of nurses, pharmacists and technicians in the oncology setting as how therapeutic agents are received, stored, inventoried, managed, mixed, delivered, administered and disposed. Since this is a well worn subject that has been reported on numerous times in the literature it may be of benefit to use the basic principles of journalism to make this education piece serviceable. For those who do not recall the basics, they consist of asking the five W's: Who, What, Where, Why and When. We will endeavor to answer all of these as we review this topic. Why? Why do we care about the safe handling of drugs deemed by others to be hazardous? The simple answer is because the majority of these hazardous drugs are cytostatic or cytotoxic agents used in cancer chemotherapy that are widely in use in physicians offices, outpatient clinics and hospitals all across North America. To date we have not come up with a definition of safe exposure we assume that any level of exposure is bad. We do not know at present if this is accurate but it is what we currently have to face in the realm of working with hazardous drugs. Here we need to define terms to explain plainly the safety concerns that are widely acknowledged. According to the HCS (Hazard Communication Standard) from The Occupational Safety and Health Administration (OSHA), a branch of the federal government, the term hazardous refers to any chemical/agent/drug that is a physical or health hazard. This seems fairly simple and straightforward. A health hazard is further delineated as something for which evidence in at least one study provides statistically significant evidence that acute or chronic health effects may occur in those exposed. (1) There have been numerous terms used and defined over the decades but the most recent stem from the 1990 Technical Assistance Bulletin (TAB) from (then) American Society of Hospital Pharmacists (ASHP) (2) that proposed criteria which were adopted by OSHA in their 1994 guidance in the form of a HCS and further refined in the National Institute for Occupational Safety and Health (NIOSH) alert of 2004. (3) This brings us back to the TAB that was updated and published most recently by ASHP in 2006. As a caution, if the reader is searching for the 2006 updated TAB it entitled the ASHP Guidelines on Handling Hazardous Drugs. (4) For our purposes we will define Hazardous Drugs (HD) as those that possess toxic properties and may therefore cause and one or combination of the following [NIOSH 04 Alert Appendix A]: 1) carcinogenicity 2) teratogenicity or other developmental toxicity 3) reproductive toxicity 4) organ toxicity (at low doses) 5) genotoxicity (mutagenicity) 6) structure and toxicity profiles of new drugs that mimic existing drugs determined to be hazardous by the above criteria So the answer in a nutshell as to why we care is listed as items one through six. To be clear about a subject that is viewed with much fear but little in the way of concrete answers to questions of down stream, long term risk, it helps to further review these and explain these terms. Carcinogenicity refers to anything that is directly involved in the genesis and promotion of cancer. Carcinogens can be of drug, radioactive substance, asbestos or even tobacco smoke origins. The action is clear but the mechanism can be varied. A carcinogen may cause direct harm or it can simply impair the multiple redundant repair mechanisms in an organism to prevent going down the path of developing a cancer. We refer to any agent or drug that can induce genetic damage in offspring as being teratogenic as it extends beyond the current generation. In this expanded definition note that the term includes harm that ranges from not being readily apparent to so harmful that miscarriage is the inevitable result. Examples of this would be high, ionizing radiation from multiple sources, viral infections, certain syndromes involving poison and similar situations where the poison is a drug or pharmacologic agent actually intended to treat or cure disease. Examples of such agents would be cis-retinoic acid or diethylstilbestrol; where there is a therapeutic benefit to be had for the patient but still risk to the unborn. When the term reproductive toxicity is included with teratogenicity the implication is that sterility or reduced capacity for reproduction are likely outcomes. This can be either acute or delayed. It can be insidious in that it reduces the reproductive window to an artificially low mark while not causing out and out sterility. Organ toxicity is dependant on the organ system referred to. For example the lungs can be the initial problem with inhaled substances but then when absorbed; the agent may go on to cause further harm in other or added organ systems. The single largest organ in the human body is the skin and as such is a likely avenue of intake into the body. It can be either the organ system affected as in the case of a rash or other dermal eruption or as we saw with the example of the lungs, a means to another toxic ends. Since the distinction takes on elements of adverse reactions from drugs dosed at therapeutic levels the addendum at low doses brings about the concern that this occurs with even trace contact or contamination. When an agent is mutagenic it refers to changes in genetic information of life. Literally it means a change in information stored at the DNA level. Recently the newer term genotoxicity has come to somewhat supplant the term mutagenic which is probably more familiar to the reader. While mutagens induce mutations there are other sources and indeed scientists believe there to be a background level found in nature. Unfortunately we do have evidence to suggest that mutations lead to cancer which is of paramount concern when it comes to handling drugs that can cause directly or indirectly, this effect. Mutagens are typically considered to be carcinogens implying that the changes to the genetic material are making cancer a likely outcome. Lastly, we have been able to make class assumptions as our ability to better define agents has improved. In the current era we have computer modeling and better analytical equipment to study new agents as they are commercially produced. In the not so distant past a drug would have years and perhaps a decade or more of study before becoming an agent approved for human use. While this was without the aid of much of our modern technology, it did allow for better classification and understanding of a drugs toxicity profile. Currently we have a much more rapid progression of agents into the common, commercial use. We now rely more on our ability to classify agents and as such we can predict that if a new agent from an existing class is produced it is a simple matter to lump it into the same profile as existing agents in that class until proven otherwise. The ultimate goal here is to protect from occupational exposure and as such it was designed to err on the side of caution. While this gives us a pressing reason for caring why we care, there is also the more mundane answer which involves regulatory compliance and ultimately ethical standards. Agents that can cause mutagenic, carcinogenic or teratogenic effects must be contained and there have been multiple attempts to categorize a uniform approach to their safe handling which the balance of this continuing education exercise will be exploring. Now that we understand why these agents are of concern and interest, the next question in the journalistic vain is what? What data do we have to support the concern? In truth there is slim data that answers objectively what we currently know for certain many years after exposure to a HD. In many cases the answers will require several decades of time after exposure to know exactly what the risks are. In order to answer what completely we need to skip ahead to who or whom? Who is it that determines whether or not a drug is a potential problem? The concern comes from linking what we know for certain and what we suspect. This is best done by either the government agency with resources or the professional societies, which have membership with the requisite expertise. Several organizations have been leading the charge as it where in the dissemination of information and they are OSHA, NIOSH, and ASHP. In 2004, the National Institute for Occupational Safety and Health (NIOSH) urged health care workers, employers, and safety professionals to take immediate action to reduce the risks from a newly identified occupational hazard: exposure to antineoplastics and other hazardous drugs. (6) Consider that chemotherapy in some form has been around since the 1950's so this alert might appear to be about half a century late. Still, there was comparatively little known about cellular biology in the middle of the 20th century compared with the current modern era and even now we admit that some useful information still eludes us. NIOSH was established by the Occupational Safety and Health Act of 1970 which also established the Occupational Safety and Health Administration (OSHA). Although NIOSH and OSHA were created by the same Act of Congress, they are two distinct agencies with separate responsibilities. NIOSH is in the U.S. Department of Health and Human Services and is primarily a research agency. OSHA is in the U.S. Department of Labor and is responsible for creating and enforcing workplace safety and health regulations. NIOSH and OSHA often work together toward the common goal of protecting worker safety and health. (7) NIOSH is moreover, a part of the Centers for Disease Control and Prevention which is funded under the Department of Health and Human Services. It has the power to issue advisory statements but is not vested with executive authority. NIOSH is probably more familiar to healthcare workers for its standards on respiratory fit testing for masks. This has become a requirement in the hospital provider community not because of it's origin with NIOSH but because it has been adopted as a standard by the Occupational Safety and Health Administration (OSHA) which does have executive authority. So to reiterate, NIOSH researches and makes advisory statements and OSHA, when a statement needs to be enforced for worker safety, enacts it into statutory regulation. We find ourselves with an advisory statement in the 2004 alert but it has yet to be made into a statutory regulation by OSHA, although some might argue that the United States Pharmacopoeia (USP) Convention has taken some elements of the 2004 NIOSH alert seriously enough to revise USP797 in late 2007 to incorporate elements of hazardous drug storage, preparation and management. (8) Now that who has been fleshed out, let us return our gaze to the question of what posed earlier. What data is available and what recommendations are there? The NIOSH alert was a 93-page document with specific warnings and lists of relevant suggestions to workers and employers on exposure prevention of the 138 drugs listed as a sample in Appendix A of the alert. The specific verbiage of the NIOSH alert is excerpted as follows: Health care workers who prepare or administer hazardous drugs (e.g., those used for cancer therapy, and some antiviral drugs, hormone agents, and bioengineered drugs) or who work in areas where these drugs are used may be exposed to these agents in the workplace. (9) This is very relevant to any discussion on the topic of safe handling of hazardous drugs. The current website for the entire document in PDF format is found at http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf That listing was compiled from multiple sources but for those who have followed this subject, it merely reinforces the 1994 OSHA HCS (hazard communication standard) requiring all employers to create or develop an inventory of all hazardous chemicals in the workplace. As a reminder in the hospital setting this is managed or made possible by the exhaustive Material Safety data Sheets (MSDS) in big binders throughout the work environment or even now possibly available in wider distribution as electronic documents. It is prudent to mention at this point that those where never intended to be static but living in the sense that they are continually being updated with new data sheets if a listing is amended or for new agents as they become commercially available and are stocked or even can include investigational agents if a MSDS sheet is available. (10) About 5.5 million U.S. health care workers are potentially exposed to hazardous drugs, including pharmacy and nursing personnel, physicians, environmental services workers, workers in research laboratories, veterinary care workers, and shipping and receiving personnel. While it may seem ironic that the very health care team, whose mission is caring for the sick, is itself a high-hazard industry for the workers it employs. In fact, published studies have shown that workplace exposures to hazardous drugs can cause both acute and chronic health effects such as skin rashes, adverse reproductive outcomes (including infertility, spontaneous abortions, and congenital malformations), and possibly leukemia and other cancers. (11) The health risk depends on how much exposure a worker has to these drugs and how toxic they are. Additionally but not really explained in the literature is that every worker brings a unique genetic predisposition and exposure history of other assaults on their genome such as high ionizing radiation and viral exposures that may have been sub clinical. The result is that it is impossible to predict with any certainty what can be expected. Workers can be protected from exposures to hazardous drugs through engineering, administrative controls, and proper protective equipment. NIOSH had an update meeting in August of 2007 to update the list of hazardous drugs as well as discuss issues that have yet to be resolved. The U.S. health care industry is one of the fastest growing sectors, with over 14 million workers in 2006 with another 3 million jobs estimated to be created between 2006 and 2016. (12) Again, today there are an estimated five and a half million of these health care workers potentially exposed to hazardous drugs or drug waste and that aside from the expected cast of characters, including pharmacists, nurses, physicians, maintenance workers, operating room personnel; others who may come into contact with these drugs while performing their job could include secretaries, drug representatives, shipping and receiving personnel in addition to family and friends that many times accompany patients into the treatment areas for moral support while the patient is receiving therapy. We have already determined that hazardous drugs are those that have been determined through research studies to have a potential for causing harm to healthy individuals, including potential risks of cancer, skin rashes, birth defects, and reproductive toxicity. These same drugs also play a critical role in treatment of patients with serious illnesses like cancer and HIV infection. Although the potential therapeutic benefits of hazardous drugs outweigh the risks of side effects for ill patients, exposed health care workers risk these same side effects with no therapeutic benefit. Health care workers can be exposed through inhalation, skin contact, skin absorption, ingestion or injection. Because of the multiple routes of potential exposure, NIOSH recommends a comprehensive approach to minimizing worker exposure. This comprehensive safety and health program should include engineering controls, good work practices, and proper personal protective equipment. In addition to these aspects of the program, NIOSH is also recommending that a medical surveillance program be used to support these efforts, collecting and interpreting data to better find out if there are changes in the health of workers. (13) A new report from the National Institute for Occupational Safety and Health (NIOSH) recommends that employers institute medical surveillance programs for health-care workers who are occupationally exposed to hazardous drugs, and suggests practical strategies and components for such programs. The document, Workplace Solutions: Medical Surveillance for Health Care Workers Exposed to Hazardous Drugs, supplements previous NIOSH resources that highlighted potential health risks for health-care employees who are exposed to hazardous drugs. A primary goal of any medical surveillance program would be to establishing a baseline for individuals'' health and then to have in place systems for monitoring their health over time. NIOSH Director John Howard, M.D. has commented that the, recommendations in this document, which were developed in partnership with health care professionals, offer practical and effective measures for instituting and maintaining safe, efficient procedures for handling hazardous drugs. NIOSH outlines the basic elements a medical surveillance program should include to help employers establish this plan and ensure that those workers who are exposed to hazardous drugs are routinely monitored. The basic recommendations include these: Health questionnaires Laboratory tests Physical examination completed at the time the worker is hired, and updated periodically. Follow-up with those workers who have shown changes in their health or have had a significant exposure. (14) It should be noted that no system will be perfect in scope or surveillance as long as we have imperfect understanding of the all the effects of HD were are using. Establishing a medical surveillance program does help to detect changes in workers health, allowing employers to evaluate the current practices to see if changes are needed to help protect other workers from exposure. Obviously to be of use, records for this sort of program needs to be held in perpetuity or until the person under surveillance is deceased. As an alternative, a 30 year period has often been used when trying to put a time limit on retention of records. [I know this is used but could not trace the origin of the 30 years number used frequently among management] When? This is an interesting query, which leads us again back to the data available. While it has been stated that the first chemotherapeutic drugs were made available over 50 years ago, it was in 1979 approximately 30 year ago that a rather startling discovery was made. The journal Lancet published the report of researchers form Finland that had discovered mutagenic substances found in the urine of nurses on hospital chemotherapy wards. Those nurses were preparing and then administering doses of chemotherapy for patients. (15) (16) While not quite the lightning bolt it would be today, it did at least provoke further study and we have seen multiple citations in the literature from that point on until the present day. Most of the work has focused on environmental controls or admixture technique and devices for further reduction of contamination. Even in these later studies there was still some contamination with multiple attempts to manage or improve outcomes have been published and republished but still they are almost never entirely free of contamination. The probable answer to the baseline contamination was first published in AJHP in a 2005 article as an exhaustive report on the extent of contamination of drug vials coming from the manufacturer. In this article we have what could be called damning evidence that no matter how many alerts or statutes were issued, nothing can take something contaminated from the beginning and hope to end up with a cleaner product in the end. At present, after the article exposed a glaring problem there has been no agency that has sprung into regulatory action and the PhRMA industry has not come forward as yet with a comprehensive plan to limit or even reduce vial contamination. Vials alone were tested and this has left all concerned to ponder the potential contamination of the package inserts and individual carton containers that the drugs are shipped inside. (17) A recent editorial in AJHP reiterated a charge to Demand Clean Vials (18) and while certainly the appropriate course of action, it will likely require pressure from the professional associations on PhRMA to affect a solution. The other alternative is for a governmental agency such as NIOSH to issue a separate alert and then another agency like OSHA to enact a regulatory statute and enforce it. Regardless of the outside community's activity, the reader should be aware that the current state of vials (and probably package inserts and the inside of shipping containers) arriving for use is to be held as highly suspect and indeed treat that receivable as a HD and use the same personal protective equipment (PPE) for its receipt as used in its admixture or administration. While many hospital providers do this, many do not and even fewer physician practices report handling HD receivables in this manner. The question of where will be taken to mean where these guidelines, alerts and activities are designed for and are complied with the HD clean room. We will therefore look at the various and sundry containment methodology available in the marketplace today and to compare and contrast them in addition to reviewing the expertise needed manipulate them and (hopefully) provide the maximal protections from HDs. The perfect environment will probably elude most as the space, materials and design elements needed are not too complex in and of themselves but become more so when combined and forced to function in a process that still requires efficiency and real time turnarounds. By that there is no implication of a wink and a nod that these are impossible tasks and therefore it is an option to give up before even starting, but it is an acknowledgement that this is difficult. As with anything that has morphed and evolved with time most clean rooms have grown up around existing space and equipment and the options for containment and safety have become somewhat limited. For the program starting from scratch it is important to consider location. All guidance now recommends venting ventilator cabinet air 100% to the outside and that can be fraught with difficulty if the HD clean room is buried in a basement or deep in a multi storey building. If in a hospital or attached on the campus of a hospital, the HD clean room will be reviewed by the Joint Commission, the department of health from the state and potentially the board of pharmacy and any other agency that claims dominion over the safe handling of hazardous drugs. In the private setting the surveying option is unlikely but the provisions of the new updated USP797 apply to all areas where sterile drugs are prepared and this does apply but again it is questionable what regulatory oversight will exist in an environment that requires only a business license from the municipality to set up an office practice. Still, the provisions of USP797 are all encompassing and are to govern the preparation of sterile products universally. Containment options suggest that all HD are stored under negative pressure so as to minimize their potential for contamination. Additionally, they should be made in an environment that controls airflow and again is under negative as opposed to positive pressure as found in requirements for the preparation of sterile products. The frequency of air changes and proof that this occurs are new additions where as before proof lay with the surveyor it now is beholden on the facility to prove they are in compliance. While that is important it should also being remembered that the vast majority of these agents will also need to be sterile preparations and as such still are required to fully comply with the other points of the USP797 statute. (19) Workers can be exposed at multiple points, such as inhalation of aerosol and particulate matter, accidental injection or exposure through accidental sharps contact, touch or dermal contamination, oral ingestion via food or oral/mucosal contamination with hands. Of these the dermal contamination does have substantial corroboration and is a common enough event in the HD preparation activity that it may account for the majority of failures. The 2006 ASHP guidance document calls for the creation of a safety program that fully captures all of these elements and recommends a collaborative approach since a comprehensive plan encompasses various disciplines such as nursing, pharmacy and housekeeping, maintenance and human resources among others. A basic element is the MSDS that was required by the OSHA HCS from 1994. All storage areas for HD should have appropriate storage and handling procedures. The recommendation is for double gloving and sealed containers to minimize the chance of breakage or even worse, dropping of HD vials. In addition to collaboration the concern is to minimize exposure through the restriction to only necessary personnel that have been trained and are documented as competent in handing HD. (20) The physical plant requires all surfaces to be washable and no non-wipable surfaces should be allowed (i.e. no upholstery or carpeted areas). The design is required to be that of areas that are easy to clean and to be sequestered away from break areas or common rooms to prevent unnecessary exposure. Regardless of location, the recommendations clearly cite the need for spill kits and the training of staff necessary for their appropriate use. The area should be positive pressure ISO Class 5 clean rooms with ISO Class 7 anterooms. This is now clear that the solution in the conflict between NIOSH and USP is solved by separating the clean room functions into two separated and distinct areas. (21) Ventilation controls are required in all USP797 compliant clean areas. More importantly they can eliminate or greatly reduce possible exposure to multiple hazards. Ventilated cabinets are the most common use but now ventilation controls in the preparation room are also necessary to keep either negative pressure in the case of HD or positive pressure where simple sterile preparation is being conducted. The most common ventilated cabinet is the Class II Biologic Safety Cabinet (BSC) followed by the Barrier Isolator (BI). Class II BSCs have been in use for decades and have been shown, when used alongside proper technique, to reduce the exposure of the operator to the hazard being manipulated. The concerns stem from three limitations reported in the 2006 ASHP guidance, namely: 1) contamination on the outside of vials from manufacturers and distributors, 2) work practices required to achieve maximal use of the ventilated cabinet are either not taught or adequately adhered to, 3) potential vaporization of HD may render the high-efficiency particulate air (HEPA) filtration system less than effective. Because of these concerns many of the current requirements for hood engineering controls require the venting to the outside of 100% of the HEPA filtered air as opposed to older suggestions that preventing a certain percentage of HEPA filtered air back into the room would be acceptable. (22) An alternative that is used far less although it is new to the US is a glove box or BI (Barrier Isolator). The BI is still a ventilated cabinet but one that allows the used to manipulate the contents via a fixed gloved access port in a seal unit. A concern exists in that these function by containment rather than use of ventilation and proper technique as stated in the National Institute for Occupational Safety & Health, NIOSH alert of 2004. To paraphrase the group Blood, Sweat and Tears (ironically the perfect name for a band reference to safe handling of HD), what goes in must come out and at some point the containment vessel can become a nidus of contamination potential. The BI has to be shown to be reproducibly decontaminated but again, technique and use will dictate how effective this procedure is. There is a concern in the containment community that the use of BIs actually take longer but as with any equipment and employee training the speed with which they are used is dictated more by safe technical acumen rather than equipment limitations de facto. That being noted, they are used in a vast minority of places in favor of the Level II BSC. (23) In 1999, a study was published in the American Journal of Health-System Pharmacists that reported on contamination of targeted hazardous drugs (Ifosfamide, Cyclophosphamide and Fluorouracil) in pharmacy mixing cabinets and surrounding areas and drug administration areas at three hospitals in the United States and three in Canada. Substantial levels of contamination from three antineoplastic agents were detected on a variety of surfaces in pharmacy drug preparation areas and drug administration areas in six cancer treatment centers in Canada and the United States. (24) This demonstrated quite clearly that surface contamination was an issue regardless of resources or expertise and that something else was needed to reduce contamination. Currently, there are multiple systems available in the marketplace to serve as an adjunct to the ventilator cabinets to contain and avoid exposure of HD. These can be further divided into systems that filter or in some means baffle or minimize contamination and those that are truly closed systems. At present there is not a distinction in the reimbursement world (none are separately reimbursable) by professional organizations but there is a difference is contamination potential. A closed system does not allow any vapor, air or particulate matter into or out of the system once introduced. In 2000 the PhaSeal Closed System Transfer Device (CSTD) was brought to the US market. Since then it remains the only closed system drug transfer device that has demonstrated no potential for leaks or escape of aerosolized or volatile vapor. In 2002, the Amercian Journal of Health-System Pharmacy (AJHP) also reported on another study looking at reducing contamination using very sensitive diction methodology and concluded that CSTD used in conjunction with the Level II BSC appeared to contain surface contamination for the hazardous drugs studied. (25) This was followed a year later in 2003 with very similar results on a slightly expanded scale with the only difference in this study being the analysis of urine for hazardous drug contamination in workers. The results demonstrated that before the use of the CSTD there were 5 of 8 employees with detectable levels of hazardous drug in their urine and after the implementation of a CSTD there was none. (26) Finally, in 2006 another study was published in AJHP that again looked at surface contamination and the use of CSTD in conjunction with Level II BSC and found a significantly reduced surface contamination as opposed to standard practices alone. (27) All of the above studies were conducted using the PhaSeal CSTD as it is a closed system needed to contain any hazardous drug contamination. A poster by Jorgenson demonstrating the integrity of dry connections was done by the University of Utah and presented at the ASHP 2007 Midyear Clinical Meeting. This poster evaluated four drug-transfer devices using an alkaline liquid for transfer as a surrogate for a hazardous drug. Litmus paper was then used as an indicator of whether or not the connections were indeed dry as witnessed by no color change or wet which would transform the litmus paper anyplace it came in contact with the alkaline solution or its residue. Each system was given 10 manipulations in all. The other three had 100% litmus change documented but the PhaSeal CSTD had none in any of the 10 manipulations. (28) A second poster from the University of Utah was presented at the 2007 ASHP Midyear Clinical Meeting by Au and Smith which evaluated nine drug-transfer devices using titanium tetrachloride (TiCl4) used as a vapor surrogate as it smokes in contact with the moisture in room air. The nine photographs of the drug-transfer devices demonstrate the release of the TiCl4 with the exception of the PhaSeal device which reinforces its distinction as the only CSTD currently available. (29) [see appendix for a list of devices that failed?] Further, the author has been a part of a pilot study conducted in concert with several cancer center to determine if the use of a CSTD (PhaSeal) was capable of reducing the exposure of HD. We found that it did reduce the detectible contamination and this was before the publication of the ASHP seminal citation on outside vial contamination awaiting publication with ASHP. When reviewing the basics of Personal Protective Equipment (PPE) it is best to begin with the three Gs: Gloves, Gowning and Goggles. In actuality, the single most important thing is for all who are involved with HD to don protective elements uniformly. If one member of the group decides for themselves that these rules are not really necessary and just a bother or a hindrance, they thereby put everyone a possible risk. Touch contamination will be a high risk for that worker indeed but in addition it will place a higher risk via touch recontamination of all others outside of the area of containment. Examples that illustrate this can be seen if an employer or risk manager uses a dye that fluoresces on exposure to ultraviolet light. Following the clean room and then all other places that the workers left traces is sometimes the best possible lesson and drives home the point dramatically. It even can have enormous peer pressure to be sure that policies and procedures are followed to the letter. Gloves are a basic and most essential part of any program of compliance. The use of gloves is recommended in USP797 and going one further, NIOSH recommends double gloving with HD and then only using thicker latex chemotherapy gloves. Gloves are to be changed whenever they are compromised or when the user has excess perspiration or at the very minimum every 30 minutes under hazard conditions. Gloves should be powder free and of a good fit to prevent hand fatigue. Hand fatigue is something that can occur with thicker Chemotherapy gloves. A worker will be flexing their hands to the point of fatigue fighting with tight gloves or perhaps is not accustomed to working with HD after a hiatus. Regardless, the potential for accidents or loss of fine motor control should be assessed when choosing a thickness of glove, while keeping in mind the need to provide a durable barrier from the HD and that many tests of integrity have been conducted with static gloves; that is to say they were not in motion or flexing as they would be in a true hazard environment. (30) There are multiple citations in the literature regarding the use of latex of both the thin exam variety and the thicker Chemotherapy sort and even nitrile, polyurethane and neoprene types of gloves. Regardless, the use of the gloves appears to be most important and we will not go into depth here other than to reference the body of literature for further follow-up. (31) (32) Gowns are also recommended by both USP797 and NIOSH but are not in total confluence as to their composition. It was previously recommended that gowns be lint-free and impermeable to chemotherapy. Regardless of the gowns used the biggest barrier to their appropriate use has been that the most effective gowns are uncomfortably hot to wear. The USP in their last 2007 revision did acknowledge this and recommended a very cool climate control of less than 68 degrees farenheight for management of the HD clean room to stimulate compliance with the gowning procedure. Again, protection from the HD is a primary role of a gown. Alongside gowning is the need for hair covering and foot coverings. Because the floors may be a source of contamination, the use of gloves when removing foot coverings a recommended. (33) Goggles are actually not used primarily because of BSCs or BIs that provide protection for the eyes of the operator. In the event that there is perceived risk the use of a face shield is now preferable to goggles in that shields more of the face when worn appropriately. The use of a respirator can also be appropriate as opposed to a surgical mask which is in no way acceptable as it is ineffective. In order for a respirator mask to be used properly it needs to be fit tested per NIOSH standards in the literature before being put into use in a hazard situation. (34) The environment in the ventilator cabinet (be it a BSC or BI) requires several other management and operational efficiencies. The admixture of chemotherapy or other hazardous drugs should be added to intravenous (IV) bags only after the IV Bag has been spiked and the uncontaminated IV solution has been allowed to prime the tubing now attached to the IV bag. Technique for doing this still will require that this is done consistent with sterile preparation goals in mind. In addition, the inside of either a BSC or a BI are considered contaminated and the very act of setting an IV bag with tubing attached inside the vessel and then affixing primary and auxiliary labels is fraught with problems and the possible risk of again spreading that contamination to the outside of the IV bad and or tubing and then out to the area where the administration will take place. Consider too what we established earlier that only recently have the vials themselves that are placed in the ventilated cabinet been determined to be contaminated on the outside and thus a source of contamination for the products we hope to admix and ultimately retrieve cleanly. The desire then is to clean off any IV solution bag before labeling and then sealing it in an appropriate transfer storage bag but again, the same issue remains of not contaminating it by setting it down on preparation areas that may be contaminated. (35) The cleaning, sterilization and decontamination of ventilated cabinets and other work areas are not only required but can again spell success or disaster in that an ineffective cleaning or decontamination procedure will only expose more than it protects. The recommendations are that ventilated cabinets, internal counters and carts cleaned each shift and as needed thereafter. Workroom counters and floors to be cleaned daily and walls, ceilings, the tray in the BSC and any shelves should be cleaned monthly. The materials necessary for cleaning need to be non-shedding on that they do not generate particles that in this case would be contaminated. (36) (37) Waste Disposal is another area that training is necessary in that housekeeping and maintenance personnel need to be trained in addition to the primary workers performing admixture of the need to treat HD disposal with appropriate care. Waste streams can be divided into trace and bulk chemotherapy with the definition of trace often cited as not being concentrated or raw chemotherapy/hazardous drug(s). Bulk Chemotherapy or hazardous drug(s) are the vials of concentrated agent with no further dilution. Most states will have specific requirements as to how to separate the waste streams and what each is constituted of to be eligible for appropriate disposal. The risk of HD is primary but if a patient has contact and therefore the waste has an infectious component as well it will need to be considered as well. (38) This brings us to training. Training is perhaps the largest element in that it involves the wildcard of the human element. All other aspects of a safety program can be perfect and a poorly trained or untrained operator can circumvent almost every safety measure without mush effort. The training should be done by supervisors who can and do demonstrate the techniques and can observe and correct in real time. Training should be documented and then competency should be assessed periodically and documented. This is a small paragraph at the end of this continuing education booklet and yet it cannot be stressed enough as to the importance for success that training will bring. Good training will empower a staff to follow procedure and know they are in the right by doing things as per protocol. Unfortunately bad training can leave workers confused or feeling like they are on their own to determine what is expedient rather than what is safe. For those who read this and are daunted by the enormous amount of effort and complexity in such an undertaking the most important thing you can do is start a Hazardous Drug Safety Review if you do not have a program in place. If you have a program in place, then update it and review the program in line with the NIOSH 2004 alert and the late 2007 revision of the USP 797. Lastly the ASHP 2006 Guidance for handling hazardous drugs should be of great assistance in making sense of a complex nexus of guidance, statutes, regulation and ethical standards to protect workers. The final word is far from being written but as our understanding of HDs and their interaction in the environment of care and among the workforce grows, so too will our comfort at knowing what the best solutions will be. Ethical standards can be of some guidance here as we have less than ideal clinical data regarding safe levels of exposure to work from. Until that time when we can predict future outcomes from exposure, it is prudent to err on the side of caution and apply the tenets of risk manage which seek to avoid risk where possible. Finally the first tenet of medicine, usually applied to patients, but adapted here for the workers in medicine is most appropriate - First, do no harm. ENDNOTES: 1) OSHA Website www.osha.gov accessed 4/30/08 2) AHJP Vol. 47 May 1990 pp 1033 - 1049 3) NIOSH Publication 2004-165 (http://www.cdc.gov/niosh/docs/2004-165/) 4) AJHP Vol. 63 June 15, 2006 pp 1172 - 1191 5) NIOSH Publication 2004-165(http://www.cdc.gov/niosh/docs/2004-165/) Appendix A 6) AJHP Vol. 61 May 15, 2004 pg 972 (pp 972-978) 7) NIOSH Website www.cdc.gov/niosh accessed 4/23/08 8) USP 797 Revision (http://www.usp.org/pdf/EN/USPNF/generalChapter797.pdf) accessed 12/4/07 9) NIOSH Publication 2004-165 (http://www.cdc.gov/niosh/docs/2004-165/) 10) AJHP Vol. 61 May 15, 2004 pg 972 (pp 972-978) 11) NIOSH Publication 2007-117 (http://www.cdc.gov/niosh/docs/wp-solutions/2007-117/) accessed 4/28/08 12) U.S. Department of Labor Web (http://www.bls.gov/oco/cg/cgs035.htm) accessed 4/28/08 13) NIOSH Publication 2004-165 (http://www.cdc.gov/niosh/docs/2004-165/) 14) NIOSH Publication 2007-117 (http://www.cdc.gov/niosh/docs/wp-solutions/2007-117/) accessed 4/28/08 15) AJHP Vol. 62 March 1, 2005 pg 471 Luci Power, MS Demand Clean Vials 16) Lancet Vol. 1 1979 pp 1250-1 (letter) 17) AJHP Vol. 62 March 1, 2005 pp475-84 18) AJHP Vol. 62 March 1, 2005 pg 471 Luci Power, MS Demand Clean Vials 19) USP 797 Revision (http://www.usp.org/pdf/EN/USPNF/generalChapter797.pdf) accessed 12/4/07 20) AJHP Vol. 63 June 15, 2006 pp 1172 - 1191 21) USP 797 Revision (http://www.usp.org/pdf/EN/USPNF/generalChapter797.pdf) accessed 12/4/07 22) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix A 23) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix B 24) AJHP Vol. 56 July 15, 1999 pp 1427 - 1432 25) AJHP Vol. 59 January 1, 2002 pp 68 - 72 26) AJHP Vol. 60 November 15, 2003 pp 2314 - 2320 27) AJHP Vol. 63 September 15, 2006 pp 1736 1744 28) ASHP MCM 2007 Au & Smith Poster (http://www.carmelpharmausa.com/econtent/35) accessed 4/30/08 29) ASHP MCM 2007 Jorgenson Poster (http://www.carmelpharmausa.com/econtent/35) accessed 4/30/08 30) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix C 31) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix C 32) AJHP Vol. 56 December 1, 1999 pp 2450 2453 33) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix D 34) AJHP Vol. 63 June 15, 2006 pgs 1175, 1180 35) AJHP Vol. 63 June 15, 2006 pp 1181-2 36) AJHP Vol. 63 June 15, 2006 pg 1183 37) USP 797 Revision (http://www.usp.org/pdf/EN/USPNF/generalChapter797.pdf) accessed 12/4/07 38) AJHP Vol. 63 June 15, 2006 pp 1183 4

Conjunctivits-When is self-care appropriate?

2007-11-01T13:00:00Z

Instructor: Doris E. Hinton, R.Ph.

Introduction Acute conjunctivitis, commonly referred to as Pink Eye, affects one in eight school children each year1, resulting in over 5 million cases in the U.S. alone2. It is one of the most frequent reasons for office visits to ophthalmologists3. Conjunctivitis rarely leads to visual loss or permanent structural damage, yet it accounts for a significant number of lost work and school days each year3. Patients primarily present with a pink discoloration to the whites of the eyes, and may also have a discharge that ranges from clear and watery, to thick and yellow-green in color. A feeling of grittiness or a sensation that there is something in the eye may accompany the redness and discharge3. Traditionally, conjunctivitis has been treated immediately with topical antibiotics, despite the fact that the majority of cases are self-limiting and will resolve without treatment3. With the emergence of antimicrobial resistance and its eventual consequences, it is imperative that physicians and pharmacists discourage the inappropriate use of topical antibiotics. Measures for appropriate self-treatment and supportive care of viral and environmental conjunctivitis are available, while cases with bacterial origin may prove to be self-limiting as well4. A key role of the pharmacist is to educate patients about conjunctivitis and when self-care measures can be appropriate. Prevalence and Epidemiology Acute conjunctivitis is generally contagious, spreading quickly and easily. Although it was once thought that viral conjunctivitis is more contagious than bacterial, it is now commonly known that both forms can be spread easily5 . Left untreated, the process can last up to 10 days5. Conjunctivitis occurs in all age groups, with the largest concentration among children under 10 years of age6 (TABLE 1). A study of conjunctivitis incidence conducted at one pediatric practice tabulated an average age of 24.3 months, with a range of 2 weeks to 16 years5. Most children who visit a physician with a pink eye end up having simple, uncomplicated conjunctivitis without any other symptoms. The majority of cases in children are bacterial or viral5. The incidence of conjunctivitis tends to surge when children return to school and come into close contact with each other after the summer break. One reason that conjunctivitis is more prevalent among younger children is the sharing of toys at daycare centers. A child with conjunctivitis will frequently rub his or her infected eyes, play with available toys, and then another child will pick up the toys. Alternatively, older children sit at desks without close physical contact. However, the availability of computer kiosks at libraries and colleges is changing this dynamic5. Conjunctivitis is significantly more prevalent among females, which account for 61% of incidence6. The cornea, the clear membrane covering the colored iris and pupil, tends to cope well with minor injury and irritation. As an example, if dirt scratches the corneal surface, epithelial cells slide over the abrasion rapidly and patch the injury before infection or vision changes can occur7. The conjunctiva is the protective membrane that lines the eyelids and also covers the white portion of the eye called the sclera8. The term conjunctivitis describes a group of inflammatory conditions that can affect the conjunctiva. The most common causes of mild conjunctivitis can be separated into three classes; bacterial, viral, and environmental8. Conjunctivitis is more commonly caused by bacteria in children (50% of cases) while viral causes are more prevalent in adults3 . The common adenoviruses, which cause most colds and upper respiratory infections, are also the cause of most viral conjunctivitis. The most common cause of bacterial conjunctivitis is S. pneumoniae, with H. influenzae being a secondary causative agent5. The natural progression of the most common types of conjunctivitis is shown in TABLE 2. Corneal infection Complications associated with conjunctivitis are not common; a review of 5 randomized placebo-controlled trials showed no serious outcomes in patients regardless of whether they were in the treatment group or the control group3. Diagnosis The classic symptom of conjunctivitis is a pink discoloration and irritation of the whites of the eyes, possibly accompanied by secretions or mucous9. The type of conjunctivitis can often be differentiated on the basis of history, physical exam, the quality of eye discharge, and whether or not both eyes are affected3,5 . One study of 111 patients who were admitted to a hospital emergency room with conjunctivitis showed that a gluey/sticky eyelid with a mucous discharge was present in 96% of cases10.TABLE 3 shows the typical symptoms and pre-disposing factors associated with the main forms of conjunctivitis. Despite the fact that the specific type of conjunctivitis can often be suspected on the basis of history and a physical exam, general practitioners and pediatricians express difficulty with differentiating between bacterial and viral cases. Diagnostic tests for conjunctivitis are not routinely performed in these settings3. A UK study completed in 2001 observed general practitioners' diagnosis and management practices for acute conjunctivitis. Questionnaires were mailed to 300 GP's, and sadly, 95% stated that they usually prescribe a topical antibiotic despite 58% of them admitting that they think at least half of the cases are viral. Only 36% believed that they could accurately discriminate between bacterial and viral cases11. It is because of the difficulty in differentiating between bacterial and viral causes that it has become standard practice to prescribe a topical antibiotic2 . Most cases of conjunctivitis are examined by family practice and pediatric physicians, while about 30% of patients seek the advice of an ophthalmologist6 . Referral to an ophthalmologist may be warranted when there is blurred vision, persistent photophobia, severe pain, lack of response to topical treatment, or the cause is suspected to be a herpetic virus. Ophthalmologists can perform a slit lamp examination to determine if the infection is bacterial or viral, since there is a pupillary response to this exam in bacterial cases5 . Other ophthalmic conditions that can cause symptoms that tend to be more severe than those experienced with mild conjunctivitis include the following7: 1. Keratitis-A more serious bacterial infection experienced after severe corneal damage, such as penetration by a foreign object. Symptoms include severe pain, decreased visual acuity, and discharge from the cornea. This is the most serious complication that can be encountered with contact lens wear. 2. Ocular Herpes-A recurrent viral infection, usually caused by the HSV-1 virus that leads to cold sores. Ocular herpes is controllable, but not curable, as is the case with other herpetic viruses. Prompt treatment with antiviral agents prevents viral multiplication, and can therefore shorten the duration of the process. 3. Herpes Zoster-Caused by the varicella-zoster virus, which may travel to the head and neck region, possibly leading to a corneal lesion. The process usually resolves on its own, but antiviral treatment decreases the risk of the infection penetrating deeper into the cornea and causing scarring. Treatment and Prognosis The treatment of conjunctivitis varies by cause. Environmental conjunctivitis is usually as a result of seasonal allergies. Topical OTC antihistamine/vasoconstrictor drops, or topical H1-histamine receptor antagonists are good choices3. Viral conjunctivitis should never be treated with antibiotics, as they are not effective in these cases. The strategy of watchful waiting, which is commonly employed with acute otitis media, may be especially appropriate for adults where conjunctivitis is most often viral. Over-the-counter artificial tears can provide comfort, as may cool compresses3. One study of 200 patients observed the effect of OTC treatment versus supportive care for viral conjunctivitis. Half were given a topical antihistamine/vasoconstrictor, while the other half were told to wash their eyes with cold water and to use ice packs. Symptoms resolved for the treatment group in an average of 4.9 days while symptoms resolved in 7.86 days among the group that used supportive care. This indicates that although viral conjunctivitis is self-limiting without antibiotics, both OTC treatment and supportive care can reduce the severity and duration of the process from its natural 10-14 day course4. If the conjunctivitis is as a result of contact lens irritation, lens wear should be discontinued for at least 2 weeks. A topical steroid to be administered for 1-2 weeks may be prescribed by the physician3. Conjunctivitis of bacterial origin may be self-limiting without treatment in mild cases. A Cochrane Review sought to assess the benefit of antibiotic treatment for acute bacterial conjunctivitis by meta-analysis. It showed that bacterial cases resolved within 2-5 days in 64% of placebo-treated cases11. Additionally, a 2005 UK study published in The Lancet examined 326 children with conjunctivitis aged 6 months through 12 years. Half were administered chloramphenicol eye drops for 7 days, while the other half were given placebo. Results showed that the cure rate was 83% in the treatment group, and 86% in the placebo group. These results indicate that most cases of acute conjunctivitis will resolve spontaneously without antibiotic treatment1, and that the automatic prescribing of a topical antibiotic for conjunctivitis should come into question2. However, if the bacterial infection is considered more moderate, a 5-7 day course of treatment with a broad-spectrum topical antibiotic may be warranted3. The preferred choice is a fourth generation fluoroquinolone such as moxifloxacin, due to its tolerability, convenient 3 times a day dosing, and speed of eradicating the infection5. Consequences of Antibiotic Overuse Penicillin was first mass produced in 1943; antibiotics have dramatically reduced illness and death from bacterial infections ever since12. However, it took only 4 years for microbes to experience evolutionary changes that would make them resistant to the very life-saving drugs that once wiped them out13. Bacteria are single-celled organisms with a small number of genes. A single gene mutation can greatly affect the organism's virulence and resistance. Because these organisms divide and reproduce quickly, the new resistant mutant can become dominant throughout the microbial population when the antibiotic is present13. It is the widespread use of antibiotics, versus the controlled use only when absolutely necessary, that promotes antibiotic resistance. In fact, the Centers for Disease Control and Prevention (CDC) claim that virtually all important bacterial infections throughout the world are developing some resistance to antibiotics13. S. pneumoniae, the pathogen responsible for most AOM, is resistant to penicillin in up to 30% of cases in some areas of the U.S., and up to 11% are resistant to third generation cephalosporins15. Greater resistance has led to the use of broader spectrum antibiotics, which are generally more expensive16. This leads to even greater resistance. It is important to note that antibiotics are not effective against viral infections such as the flu, most sore throats, the common cold, and seasonal allergies. Antibiotic use in these instances is a waste of money and further exacerbates bacterial resistance14. Parental pressure to prescribe antibiotics is a big concern; a recent study showed that pediatricians prescribe antibiotics 65% of the time when they sense that the parent expects it, but only 12% of the time when they sense the parent will not pressure them into writing a prescription14. In 2002, the Council for Affordable Quality Healthcare (CAQH) surveyed 1000 adults to determine their beliefs about antibiotics and found that misperceptions persist about their appropriate use17 (Table 4). Until recently, it was thought that the use of topical antibiotic drops did not lead to bacterial resistance, since they are applied in small amounts, directly to the infected area8 . However, it is now recognized that some resistance to topical medications for conjunctivitis is developing 5. A 1988 study of antibiotic susceptibility to 1291 ocular bacterial isolates found that fluoroquinolones were the most effective class, yet 18% of staphylococci were resistant to them. These organisms were very resistant to other antibiotics traditionally used for conjunctivitis, such as Gentamicin, Tobramycin, and Erythromycin18. These results suggest that physicians that prescribe fewer antibiotics for other types of infections should be considering reducing antibiotic usage for conjunctivitis as well2. Resistance to topical antibiotics can be prevented if physicians do not automatically prescribe one for every patient with a red eye. Antibiotics should never be prescribed for viral or environmental conjunctivitis and in most cases bacterial conjunctivitis may be self-limiting as well5. Simple measures that parents can take to prevent the spread of bacterial resistance include the following: -do not expect or demand an antibiotic prescription with every physician visit. -do not take an antibiotic for a viral infection. -understand that antibiotics are not appropriate for some bacterial infections. -Unless advised otherwise by a physician, complete the full course of an antibiotic prescription. -never save some of an antibiotic for the next time you get sick. -never take an antibiotic prescription that was prescribed for someone else. In 1995, the CDC launched a national campaign designed to reduce antimicrobial resistance by educating both the public and healthcare providers.14 Pharmacists can help inform the public by providing useful educational materials to patients which can be ordered from the CDC at http://www.cdc.gov.drugresistance/community/orderform.htm#bulk. School Policies School policies that regulate absenteeism are in some cases antiquated and are largely set by the school district versus the CDC5 .The typical school policy states that children with conjunctivitis can be sent back to school or daycare 24 hours after antibiotic treatment is started8. This policy is despite the fact that experts consider the period of infectiousness to be 7 days from the onset of symptoms; some studies suggest the infectious period may be as long as 10-14 days3. Except where viral or bacterial conjunctivitis is accompanied by other signs of illness, children should be allowed to remain in school once therapy is started . Specifically, the Red Book does not recommend excluding children from school if their symptoms include only a red eye with a clear discharge with no other signs of systemic disease5. Prevention Avoiding close contact with infected individuals accompanied by frequent hand washing is the cornerstone of preventing the spread of conjunctivitis. One study showed that one school which promoted frequent hand washing or the use of hand sanitizing alcohol gel had a 50% lower absence rate versus a control school5 . The CDC has instituted the Ounce of Prevention campaign, created by the National Center for Infectious Diseases, with the goal of teaching the public the benefits of cleaning, and disinfecting, and hand washing19. Pharmacists can help with this campaign by providing consumer educational brochures, which can be ordered from the CDC at http://www.cdc.gov/ounceofprevention. Other preventive measures for reducing the spread of conjunctivitis include the following3: 1. Contact lens wearers should be instructed in proper lens care and encouraged to replace lenses frequently. 2. Eye protection should be worn when appropriate to prevent exposure to chemical and toxic irritants. 3. Daycare centers should routinely sanitize toys and surfaces that are shared by children. 4. Infected individuals should not share towels with other family members. 5. Infected individuals should never share topical eye drops with others. Over the Counter Pain Medications Topical eye drops specifically for viral and environmental conjunctivitis are now available OTC in the U.S and may be used as a safe, soothing alternative in patients over 2 years of age. These eye drops should not be used if the patient is experiencing eye pain, sensitivity to light, vision changes, a lesion on the cornea, or a thick white, yellow, or green discharge7. Patients with these symptoms should be referred to a physician. Topical antihistamine/vasoconstrictors and H1-antihistamine receptor antagonists are also available for environmental conjunctivitis caused by seasonal allergens. Over-the-counter artificial tears may be a soothing alternative as well3. Patient Counseling Patients see their pharmacist more often than any other healthcare provider; therefore pharmacists are in an excellent position to educate patients about appropriate conjunctivitis care20. Pharmacists can play an instrumental role in advising of the dangers of antibiotic over-prescribing both to the individual and to society. Pharmacists can help parents understand when antibiotics may be appropriate and when they are not. Of particular value is the pharmacist's ability to suggest OTC products and appropriate supportive measures that can be used in mild cases of viral and environmental conjunctivitis. It is important for the pharmacy technician to ensure that patients with conjunctivitis who approach the pharmacy counter be counseled by the pharmacist. Suggested points for discussion include the following: 1. Inform parents that according to studies, 64% of conjunctivitis cases tend to resolve spontaneously without antibiotics. 2. Make parents aware that avoiding contact with other infected individuals will reduce the likelihood of spreading conjunctivitis. 3. Discuss that certain daycare situations may contribute to increased incidence of conjunctivitis. 4. Inform customers that they should not share towels with family members who have conjunctivitis. 5. Consider displaying educational materials provided by the CDC for parents during critical 6. Explain the dangers of antibiotic over-prescribing to parents. 7. Educate customers about illnesses where antibiotics are not effective and are therefore not appropriate. 8. Always counsel those receiving an antibiotic to take it as directed and finish the full course. 9. Advise patients never to save antibiotics for the next illness and never to share with others. 10. Be familiar with OTC topical eye drops that may be appropriate for mild cases of acute viral and environmental conjunctivitis. Summary Acute conjunctivitis affects over 5 million people each year, yet it is likely to resolve spontaneously in 64% of instances. Due to the alarming increase in antimicrobial resistance seen since their discovery in the 1940's, antibiotics must be used more judiciously if we are to continue to rely upon them for life-threatening illnesses. Research has shown that the majority of cases of conjunctivitis can be managed without prescription antibiotics, making conjunctivitis a prime area for reducing antibiotic overuse. Over-the-counter treatments and supportive measures may be appropriate choices for most cases of mild viral and environmental conjunctivitis. Pharmacists can play a significant role in reducing the inappropriate use of antibiotics by educating consumers about proper conjunctivitis self-care. References 1. 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