THESIS HURS 1998 K656w c.2 Kolpien-Bugaj, Karen. White blood cells on gram stain as a 1998. White Blood Cells on Gram Stain as a Treatment Indicator for Chlamydial Infection by Karen Kolpien-Bugaj, BA, BSN, RNC Submitted in Partial Fulfillment of the Requirements for the Master of Science in Nursing Degree Approved by: Jy^ith S. Schilling; CRNP, PhEjZ Committee Chairperson Edinboro University of Pennsylvania bate kip 7 4? Jeanne M. Weber, EdD, CRNP Committee Member Edinboro University of Pennsylvania Date 'ta Nancy Rea, MHSA Committee Member Erie County Department of Health ______ Date c- A Abstract Chlamydia infection in the United States has the highest incidence of all infectious diseases tracked by the Centers for Disease Control and Prevention. It is often without symptoms and there is no rapid, cost-effective test method that provides both high sensitivity and specificity. Consequently, the spread of the disease often occurs by patients who are unaware that they are infected. Gram stain is one test which can be performed relatively quickly and inexpensively. Although not able to directly detect chlamydia, it is capable of detecting the presence of white blood cells (WBCs) indicative of infection. This study sought to examine what relationship may exist between either the presence or absence of WBCs on Gram stain and chlamydia infection. It also sought to identify other clinical factors with relationships to chlamydia infection. The clinic charts from 54 patients of a public health sexually transmitted diseases clinic in northwestern Pennsylvania, were reviewed. A matched groups design comparing the Gram stain WBC results of patients who tested DNA chlamydia-positive and DNA chlamydia-negative was performed. Other clinical factors were also compared between the two groups. ii The Gram stain detected 93% (P=0.00014) of the chlamydia infections present. In the group without chlamydia it erroneously predicted infection in 44% of the patients. No other factors were identified as more specific indicators of chlamydial infection. The author concluded that of the factors studied, the Gram stain was the best clinical tool for prescribing presumptive treatment for chlamydia. The data also support the literature by indicating that Gram stain is neither highly sensitive nor specific for chlamydia, and further research and better tests are needed for rapid effective detection of chlamydial infection. iii Table of Contents Chapter Page Chapter 1. Introduction 1 Background of the Problem 2 Conceptual Framework 5 Statement of the Problem 16 Assumptions 17 Definition of Terms 18 Limitations 21 Summary 22 Chapter 2. Review of Literature 24 Goals and Guidelines for Screening and Treatment 24 Diagnostic Tests 26 Screening Characteristics 29 Treatment Characteristics 34 Treatment before test results 34 Treatment after test results 35 Nurse Practitioner Role 38 Summary 41 iv Chapters. Methodology 44 Hypothesis 44 Operational Definitions 44 Research Design 46 Procedures 46 Sample 47 Informed Consent 49 Instrumentation 49 Demographics 49 Independent Variables 49 Dependent Variable 50 Data Analysis 51 Summary 51 52 Chapter 4. Results Demographic Data 52 Clinical Indicators and DNA Probe Results 52 Gram Stain Versus Other Clinical Indicators 56 Gonorrhea Versus Chlamydia Results 57 59 Chapters. Discussion 59 Conclusions v Recommendations 61 References 64 Appendixes 69 A. Application for Access to Protected Data 70 B. User’s Guide to Access to Protected Data 86 C. Erie County Department of Health STD Clinic 92 Patient Consent Form 93 D. Data Collection Spreadsheet vi List of Tables Table Page 1. Chlamydia Infection in Heterosexual Men in a Study Reported by Rietmeijer et. al. (1991) 31 2. Gram Stain Urethral Smear Results in 219 Men With and Without Urethral Discharge from a Study Reported by Janier et al 33 3. Patients With Positive Screening Tests Who Were Not Treated at Initial Visit, and Time Intervals Until Treatment Was Received, in a Study of 24,823 Patients 36 by Schwebke et. al 4. Criteria For Presumptive Treatment for chlamydia as Reported by Nurse Practitioners in a Survey Performed by Alexander et. al 40 5. Demographic Data for Study Sample Groups 53 6. DNA Probe Chlamydia Results and Results of Other Clinical Indicators in Patients From the STD Clinic in this 54 Study vii List of Figures Figure Page 6 1. The Epidemiologic Triangle 2. The Dever Epidemiologic Model 10 3. The Epidemiologic Prevention Process Model 13 4. The Holistic Epidemiologic Prevention Process 15 Model for Advanced Practice Nursing viii 1 Chapter One Introduction In this chapter, the history of sexually transmitted diseases (STDs) and their impact on the health of individuals and communities will be examined utilizing models of epidemiology as they are applied to public health and advanced practice nursing. Specifically, the need for more consistent testing and treatment guidelines for screening and treatment of patients with Chlamydia trachamatis (chlamydia) will be reviewed. The use of Gram stain and its clinical indications for the presence or absence of chlamydia are a focus. Historically, Hippocrates described syphilitic-type sores as early as 460 B.C. (Hippocrates, -460 B.C./1972). By 1953, penicillin was being heralded as “the drug which would eradicate venereal disease” (Commonwealth of Pennsylvania Department of Health [CPDH], 1970, p.17). The incidence of syphilis fell from 106,539 cases in 1947, to a low of 6,516 in 1955. With these dramatic results, funding that had supported a nationwide venereal disease program was drastically decreased. The consequences were evidenced by a rebound to more than 100,000 new cases of syphilis in 1962 (CPDH, 1970). Richard D. Lamm, former governor of Colorado and director of 2 the Center for Public Policy and Contemporary Issues at the University of Denver, has written “The Ten Commandments of Health Care” (Lamm, 1990). In it he cautions, “We must. . . establish norms and standards for diagnostic and therapeutic practice that encompass both costs and medicine” (p. 129). With chlamydia having pushed into the forefront as the leading infectious disease in the United States (Eng & Butler, 1997), the domain of public health has a challenge in effectively combating a 1990s compliment to the syphilis of the past. Additionally, it comes at a time when limited resources and increased competition within health care are mandating that financial costs be examined more closely than ever before (U.S. Department of Health & Human Services [HHS], 1994). For these reasons, it is paramount that all primary health care providers judiciously strive to identify patients at risk for chlamydia (Eng & Butler, 1997) in order to examine, test, and appropriately treat them utilizing both valid and cost-effective means. Background of the Problem Tracked for the first time in 1995, chlamydia was the most common infectious disease in the United States (Centers for Disease Control and Prevention [CDC], 1996b). The 477,638 reported cases cited in the annual report from the Centers for Disease Control and Prevention (CDC) showed the incidence of chlamydia exceeded not just other sexually transmitted 3 diseases (STDs), but all other infectious diseases as well (CDC, 1996b). The State of Pennsylvania counted 22,828 cases of chlamydia in 1995, with 825 of those being from Erie County (Erie County Department of Health, 1998). In October 1997 the report of statistics for 1996 revealed that chlamydia retained its position as the leading infectious disease (CDC, 1997d). In PA and Erie County the 1996 cases numbered 18,445 and 624, respectfully (Erie County Department of Health, 1998). Additionally, at the close of the 40th week in 1997 when the 1996 report was released, the year-to-date national case total for chlamydia in 1997, exceeded those for 1996 by 10,325 cases (CDC, 1997e). Screening for chlamydia has been deemed a priority by the CDC because 75% of infected women and 50% of infected men are asymptomatic (CDC, 1997c). In women, untreated chlamydia can progress to pelvic inflammatory disease, infertility, or potential ectopic pregnancy. The cost of treating these complications exceeds $2 billion annually (CDC, 1997c). The CDC estimated that one-half of all chlamydia cases occurred in teens ages 15 to 19, and predicted that the impact to both lives and cost could be greatly reduced by expanded screening for the disease. Although less likely to suffer from untreated complications, men have rarely been included in routine screenings. They can, however, develop sequelae such as epididymitis or 4 proctitis and their untreated chlamydial infections become a risk to female sexual partners who, if pregnant, may pass that risk onto an unborn fetus (CDC, 1996a). Because chlamydia is sexually transmitted, decreasing the incidence of this disease and its complicating sequelae must include screening and appropriate treatment for both men and women (CDC, 1996a). Traditionally, consistent guidelines for screening have been lacking due to the large number of screening tests available (Schachter et. al., 1992). Additionally, once screened, patients are often unable to be located or refuse to return for treatment. (Schwebke, Sadler, Sutton, & Hook, 1997). This has created a need for tests that provide immediate results and, in the absence of such tests, clear guidelines or indicators for presumptive chlamydia treatment (Schachter et. al., 1992). As of 1994, major medical authorities including the American Academy of Pediatrics, the American Academy of Family Practice, the American College of Obstetricians and Gynecologists, the American Medical Association, the Centers for Disease Control and Prevention, and the United States Preventive Services Task Force have advocated routine screening for STDs (Eng & Butler, 1994). Criteria for identifying patients at risk and in need of screening include all patients in STD, family planning, or adolescent clinics, as well as anyone under the age of 20 who admits to 5 multiple sex partners. They added that prostitutes, patients with a past history of STDs, or those who are untreated since sexual contact with an infected partner, should also be screened. Conceptual Framework In developing the conceptual framework for this study, three existing conceptual frameworks were reviewed. They were; a) The Epidemiologic Triangle, b) The Dever Epidemiologic Model, and c) The Epidemiologic Prevention Process Model. These models were then integrated to form The Holistic Epidemiological Prevention Process Model for Advanced Practice Nursing, used in this study. Screening has been encouraged for the identification of infection and for risk factors that, when appropriately acted upon, will prevent disease (Mausner & Bahn, 1974). Historically, the theory of epidemiology originated with Hippocrates in the 5th century B. C., in his writings titled “On Airs, Waters, and Places” (Hippocrates, -460 B. C./1972). Utilizing this premise, in 1958, Leavell and Clark (1979) developed an epidemiological concept that depicts the natural history of disease in man. It states that disease begins via a stimulus generated by interrelations between the agent, host, and environment. These three factors are depicted in The Epidemiologic Triangle (Figure 1) as the three points of the triangle. Epidemiology theory seeks to 6 ENVIRONMENT AGENT FIGURE 1 HOST The Epidemiologic Triangle (Adapted from Mausner, J. S., & Bahn, A. K.: Epidemiology An Introductory Text. W. B. Saunders Company, Philadelphia, 1974, p. 33.) 7 identify, then remove or interrupt, interrelations between these factors as a means of disease prevention and control (Mausner & Bahn, 1974). For epidemiological purposes Mausner and Bahn defined these three factors. The first, the host, is the organism whose health is being focused upon. There are conditions which must be true of the host for disease to occur. In this study the hosts were the STD patients, and sexual activity of the host would be a condition necessary for the disease of chlamydia to occur. The second factor is the agent and is something which may be present or absent, but alone is not sufficient to cause disease without certain conditions within the other two factors being met. Chlamydia is the agent that was examined in this study. The third factor is the environment. This is the surroundings of the host and contains conditions that impact the host. Often these surroundings are separated into the three categories of biological, social, and physical environments. STD patients had biologic environments (ie: individual immune status), social environments (ie: peer pressure), and physical environments (ie: accessibility to a location conducive for sexual activity to occur) as potential catalysts for chlamydia infection. As primary care providers, nurse practitioners need to be aware of which patients (potential hosts) to screen for chlamydia. They must have adequate knowledge of which testing methods will provide optimal accuracy 8 for the diagnosis and effective treatment of chlamydia (the agent). Additionally, they must be aware of methods for prevention of reinfection, spread of the disease, and complicating sequelae (environmental influences). Leavell and Clark’s (1979) model defined the point at which interrelations between the host, agent, and environment first generate a stimulus for disease as a period of “Prepathogenesis.” During this phase they cite two components of possible intervention termed “health promotion” and “specific protection.” Preventive measures implemented within this phase are called “primary prevention.” The second period of disease according to Leavell and Clark (1979), is that of “Pathogenesis.” In this phase the host produces a response to the stimulus from phase one. They listed the following three components of possible prevention within this period: a) early diagnosis and prompt treatment, b) disability limitation, and c) rehabilitation. Measures of prevention implemented in the first two they called “secondary prevention.” Any preventive measures instituted during the rehabilitation phase they termed “tertiary prevention. Primary prevention measures such as educational campaigns that focus on sexuality, condom use, disease education, and esteem building, are all utilized within the scope of public health. Secondary prevention is 9 accomplished through early diagnosis and effective treatment and has three objectives that are: a) to prevent and cure disease processes, b) to prevent the spread of communicable diseases and, c) to prevent complications and sequelae of communicable diseases (Leavell and Clark, 1979). These basic definitions of primary, secondary, and tertiary prevention continue to be utilized within epidemiology today, but have been broadened to accommodate science and medicine by taking diseases far beyond the confines of the “germ theory” (Phillips, 1986). Expounding upon the three factors of The Epidemiologic Triangle Alan Dever, health-policy analyst, created The Dever Epidemiological Model (Figure 2) (Clark, 1992). Dever identified four determinants of health status and listed three comprising components within each. They are: a) human biology comprised of genetics, physiological function and maturation, b) environment comprised of physical, psychological and social elements, c) life-style comprised of employment, consumption, and leisure, and d) health-care system comprised of availability, accessability, and utilization. Dever’s model was relevant to the STD patients in this study as follows: 1 Biology. Each patient’s genetics were individual and although patients were matched for age, gender, and race physiologic function and 10 human biology Genetics Physiologic Function Maturation ENVIRONMENT Physical Psychological Social LIFE-STYLE Employment Consumption Leisure HEALTH-CARE SYSTEM Availability Accessibility Utilization FIGURE 2 The Dever epidemiologic model (From Clark, M. J.: Nursing In The Community. Appleton & Lange, Norwalk, Connecticut, 1992, p. 114.) 11 maturation levels were unique to each patient. The numbers of white blood cells seen on each patient’s Gram stain was the biologic indicator used in the study. 2. Environment. The physical environment included the surroundings where the patient lives. The psychological and social encompassed dynamics of interpersonal relationships, values, and emotions that all influenced the choices surrounding the patients’ sexual activities. Whether the patient had contact to a sexual partner infected with chlamydia, and other sexual history of the patient were environmental indicators for infection. 3. Life-style. Whether the patients were employed or in school, and whether or not they used alcohol or recreational drugs is data that was included on the patients’ charts but not recorded as part of this study. Leisure time activities often are largely influenced by the above. The combination of these factors influenced patient choices that were determinants of patients’ health status (ie: decisions to be sexually active, have multiple sex partners, condom use etc.) As an indicator of lifestyle, patients in the study were matched as either “established" or “first visit” clients. 4 Health-care system. Patients can only utilize health care that is accessible and available to them. The clinic studied provided anonymity and 12 provided testing and treatment at no charge and offered various clinic schedules as a means of heightening availability and client accessability. T. S. Eliot wrote, “The whole earth is our hospital” (1943, p. 30). This premise has traditionally separated community or public health from other forms of health care. Specifically, in community nursing the principles of epidemiology are utilized as a foundation for practice which is geared not just to the individual but to the “whole earth,” the community. By combining the levels of prevention identified by Leavell and Clark (1979) with Dever’s Epidemiological Model, the Epidemiologic Prevention Process Model (Figure 3), utilized in community health nursing, was developed (Clark, 1992). In this model, the above four components make up “Step 111 or the “client assessment” phase of the nursing process. In “Step 2" a “nursing diagnosis” is derived from the assessment. Steps 3 through 5 utilize the three levels of prevention; primary, secondary and tertiary. Using these, in “Step 3" a nursing plan of intervention is decided upon. In “Step 4" the plan is implemented and in “Step 5" an evaluation of the outcome completes the nursing process. By building upon the epidemiologic prevention process from nursing and combining it with the holisitic approach characteristic of advanced practice nursing, The Holistic Epidemiologic Prevention Process for 13 Nursing Process Step 1 Client assessment Epidemiologic perspective Human Biology Environment Life-style Health System Step 2 Nursing diagnosis Step 3 Planning intervention Step 4 Implementing the plan Levels of prevention Primary prevention Secondary prevention Tertiary prevention Step 5 Evaluating FIGURE 3 The epidemiologic prevention process model (From Clark, M. J.: Nursing In The Community. Appleton & Lange, Norwalk, Connecticut, 1992, p. 119.) 14 Advanced Practice Nursing Model (Figure 4) can be derived (Chinn & Kramer, 1995). The components of this model are as follows: Step 1. The performance of a holistic client history, assessment, and examination. Step 2. Determination of a clinical diagnosis based upon the assessment data. Step 3. Development of a plan of treatment and/or therapy. Step 4. Execution of the plan via order, prescription, or referral. This plan may combine the various levels of prevention and may include medications, behavior modification, and lifestyle changes. It also may incorporate ancillary or alternative health care providers as needed to provide a holistic plan of care. Step 5. Evaluation of the plan, and a holistic client reassessment. The medical community has traditionally been one that is disease focused, not patient focused (Keeling, 1996). Assessment for appropriate treatment, patient education, and contact notification for communicable diseases such as chlamydia were historically referred to public health nurses and officials, who retrospectively applied principles of epidemiology to medical diagnoses and treatments already rendered. Nurse practitioners are educated to see patients holistically and provide care that incorporates 15 Advanced Practice Nursing Process Step 1 Holistic client examination & assessment Epidemiologic perspective Human Biology Environment Life-style Health System Step 2 Formulation of a clinical diagnosis Step 3 Developing a plan of care & prevention Step 4 Ordering & prescribing the plan Levels of prevention Primary prevention Secondary prevention Tertiary prevention Step 5 Evaluation & holistic reassessment FIGURE 4 The holistic epidemiologic prevention process model for advanced practice nursing (Developed by Kolpien-Bugaj, K. 1998) 16 health promotion through disease prevention and patient education, as well as to diagnose and treat the disease process (Keeling, 1996). The nurse practitioner role incorporates elements of both medicine and traditional public health which may make it one of the best suited to combat diseases such as chlamydia. To effectively do so requires that the most reliable assessment tools be utilized. If the number of WBCs on Gram stain is a valid predictor for chlamydia diagnosis, NPs could be trained to do them. If it is not a reliable indicator, are there other clinical characteristics that could be obtained using a holistic examination and assessment which would more reliably predict infection? Identifying such indicators could assist the screening and treatment of individuals with chlamydia seen in clinical practice. Statement of the Problem Documented cases of chlamydia occur in the United States more frequently than any other infectious disease (CDC, 1997c). An estimated 3.5 million cases go undetected and unreported each year with consequent lack of screening, diagnosis, and treatment largely attributed to its asymptomatic nature. There are no consistent guidelines for the detection of chlamydia. The testing methods most often used do not provide results at the time of the patient’s office visit. Once a positive result is received, patient compliance 17 with treatment follow-up is often difficult to obtain. A method for detection of chlamydia, or clinical indicators with a high positive predictive value for infection, could facilitate immediate treatment and improve the prevention and control of further disease. Because a concentration of WBCs is a biologic response to inflamation, and since an infection such as chlamydia should evoke the inflammatory response, WBCs should be present in biologic tissues infected with chlamydia. This study sought to answer the following research question: What relationship is there between the presence of white blood cells on female cervical and male urethral Gram stains, and chlamydial infection? Assumptions This study was based upon the following assumptions: 1. Guidelines for the diagnosis and treatment of chlamydia, nongonococcol urethritis, and mucopurulent cervicitis, as designated by the CDC, were valid. 2. Generally accepted performance standards had been met and maintained by all medical and laboratory personnel who performed testing, diagnosis, and treatment of patients at risk for chlamydia and related sexually transmitted diseases. 3 Patient records provided accurate information regarding medical 18 history, physical examination findings, appropriate laboratory test specimens, patient contact information, test results, medical diagnosis, and treatments prescribed. 4. Testing supplies were uncontaminated, unexpired, and capable of accurately assessing for the presence or absence of infection. 5. The presence of white blood cells on Gram stain was indicative of inflammation and/or infection due to some underlying agent of pathology, and chlamydia as an agent stimulates the presence of WBCs. 6. Untreated chlamydia could result in complicating sequelae and an increased risk of infection with the human immunodeficiency virus, (CDC, 1997c). 7. Treatment indicated that a patient received either medication, or a prescription for medication, approved by CDC guidelines for treatment of chlamydia. Definition of Terms The succeeding terms were defined for this study as follows: 1 Chlamydia trachomatis are nonmotile, obligate, intracellular parasites that were once thought to be viruses. They now are known to more closely resemble bacteria because they contain both Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) genetic material, and have a cell wall 19 similar to the one seen in Gram-negative bacteria. They are transmitted between human hosts via the contact and exchange of infected genital body fluids. They are generally vulnerable to specific macrolide and tetracycline antibiotic treatments. 2. Nongonococcal urethritis is an inflammation of the urethra with an etiology other than Neisseria gonorrhoeae or Trichomonas vaginalis (CDC, 1997a). 3. Mucopurulent cervicitis is an inflammation of the cervix with an etiology other than Neisseria gonorrhoeae or Trichomonas vaginalis (CDC, 1997a). 4. Gram stain is a laboratory test used to look for evidence of the presence of microorganisms by examination of the number and type of blood and tissue cells observed, and/or the evidence of various bacteria, following a specified staining process (Laboratory Corporation of America [Lab Corp], 1997-1998). When observed under a microscope, Gram-positive organisms will appear blue, and Gram-negative organisms will appear red (Lennette et. al., 1980). The test is useful for identifying the presence of Neisseria gonorrhoeae in genital specimens due to the distinct Gram-positive diplococci bacteria evident in gonorrhea infection. Gram stain is also a screening tool for the presence or absence of other infections, as determined 20 by the number of polymorphonuclear (PMN) white blood cells viewed per microscopic field (Lab Corp, 1997-1998). Because Chlamydia trachamatis is an intracellular organism it cannot be detected on Gram stain. Therefore, the absence of Gram-positive diplococci, and the presence of PMN-WBCs indicate an infectious process from an agent other than Neisseria gonorrhoeae. Because chlamydia has the highest incidence of all STDs, WBCs on Gram stain, in the absence of Gram-positive diplococci, may be due to chlamydial infection. 5. Transcription Mediated Amplification (TMA) is a laboratory test utilizing a Hybridization Protection Assay method. It uses specimen DNA probes that are acidinium ester-labeled, and specific to the target organism’s amplified sequence. The organism is released by either chemical or mechanical means. The TMA targets ribosomal RNA (rRNA) with the breakdown of a single bacterial cell resulting in up to 10,000 copies of rRNA being made. This gives the test an assay sensitivity of less than one cell (Hill, 1996). 6. White Blood Cells (WBCs) are immune cells that can kill many pyogenic bacteria and fungi. They are a defense mechanism of the human body, mobilized by the inflammatory response to the infection of the host by a foreign (or biologically perceived foreign) agent (Groer & Shekleton, 1989). 21 7. A specimen is a sample from a potential host of cells, tissues, or fluids known to act as a reservoir for an agent of disease (Fischbach, 1988). 8. A wet mount is a cervical mucous specimen added to 5-7 drops of normal saline on a glass slide. It is covered with a coverslip and viewed under a microscope for the presence of yeast buds or hyphae, Trichomonas vaginalis organisms, or large WBCs known as “clue cells” present in bacterial vaginosis (Carr, Freund, & Somani, 1995) 9. Presumptive treatment is any patient who received a CDC approved treatment regime for chlamydia prior to the availability of results from a laboratory test specific for chlamydia. Limitations This examination of the research question was limited by the following factors: 1. The data collected had an optimum accuracy equivalent to that which is reasonably attainable with those tests being utilized because all available methods of testing for chlamydia can give false-negative results (Eng & Butler, 1994). 2. Only data from one clinic site was utilized which decreases the generalization of the results obtained to other populations and types of medical sites. 22 3. Laboratory results were derived from male urethral or female cervical specimens and were obtained by multiple practitioners who, while following clinical guidelines, may still have some variability in clinical technique. 4. Race, gender, age, and visit status as a new patient or established patient, were all controlled for to limit bias from any of these confounding variables. Summary Chlamydia is currently being reported with a greater incidence than any other infectious disease (CDC, 1997c). It is often asymptomatic and, left untreated, can lead to costly, complicating sequelae (CDC, 1997c). Certain groups have been targeted by leading medical organizations for screening of chlamydia, in an attempt to decrease its spread by utilizing principles of epidemiology. Tests used for screening often give false-negative results, and no consistent guidelines for screening and presumptive treatment have been firmly established (Schachter, et. al., 1992). Knowledge of which patients to screen, and accurate diagnosis and appropriate treatment for chlamydia, fall within the scope of practice of nurse practitioners. With the knowledge that white blood cells are mobilized by the immune system to the site of invasion by foreign agents, it can be concluded that they would be 23 directed to the mucous membranes of the genital tracts of human hosts infected by the agent of chlamydia. Patients who exhibit symptoms related to the inflammatory response of infection, such as pain or evidence of infectious exudate in the form of cervical or urethral discharge, would be assumed to have white blood cells present as a part of this bodily response. But, what about patients who have no complaint of symptoms and no clinical signs of inflammation upon exam? Are signs and symptoms absent due to a lack of an inflammatory response or, in a Gram stain of a specimen from the site, would evidence of infection and inflammatory response be detectable by the presence of white blood cells? If so, then a Gram stain with white blood cells in the absence of any Gram-positive diplococci indicative for gonorrheal infection, could be a valid predictor of chlamydial infection. If a lack of signs and symptoms coincides with a lack of white blood cells on Gram stain in patients with confirmed chlamydia infection, then it may be a poor diagnostic indicator. 24 Chapter 2 Review of Literature In this review of literature, studies focusing on patient screening strategies, diagnostic laboratory tests utilized for screening, and approaches to treatment for chlamydia have been examined. Changes in laboratory technology and requirements, and their effect on the screening process, are discussed. The role of the nurse practitioner in effectively screening, testing, and treating patients for chlamydia is also reviewed. Goals and Guidelines for Screening and Treatment. Ideally, decreasing the incidence of sexually transmitted diseases requires that many variables be competently addressed (Eng & Butler, 1997). These include assessment of risk; laboratory testing and screening; physical examination; appropriate diagnosis and treatment; partner notification and follow-up; and patient education and counseling regarding the disease, its method of transmission, consequences of nontreatment, and behavioral change for future risk reduction. The degree to which these goals are met is often directed by the availability of resources. Traditionally, assessments of the quality of public health measures to address these variables have been limited (Eng & Butler, 1997). In a recent report, the Institute of Medicine found that, upon conducting on-;■site visits and in personal work with public 25 health STD clinics, that there was little emphasis placed on quality indicators for screening and treatment of chlamydia. Emphasis was on the number of patients screened, not upon the number that tested positive and who were adequately or appropriately treated (Eng & Butler, 1997). This finding correlated with the CDC’s (1993a) recommendations for chlamydial program evaluation. The CDC suggested that information should be gathered to provide quantitative estimates about diseases, and follow trends. This should include any interventions that are performed, and an evaluation of their impact. They further recommended that such data be analyzed from an epidemiologic perspective and be used as the basis for decisions regarding future allocation of resources and evaluation of chlamydia prevention programs. In Healthy People 2000, Health Status Objective 19.2 states, “Reduce Chlamydia trachamatis infections, as measured by a decrease in the incidence of nongonococcal urethritis, to no more than 170 cases per 100,000 people (Baseline: 215 per 100,000 in 1988)” (HHS, 1991, pp. 498). In it’s most recent treatment guidelines for sexually transmitted diseases, the CDC defined nongonococcal urethritis (NGU) in men as urethral inflammation not caused by Neisseria gonorrhoeae. The diagnosis of urethral inflammation is based upon the presence of urethral discharge, the presence 26 of white blood cells (WBCs) on a Gram stain smear, or a positive urine leukocyte esterase test (for any man under 60, who has no history of urogenital diseases). A diagnosis of NGU also requires that no laboratory evidence of N. gonorrhoeae be detected (CDC, 1997a). Women may also get urethritis from various agents, including chlamydia, but they are more often tested and evaluated via endocervical specimen. The CDC defines mucopurulent cervicitis (MPC) in women as cervical inflammation that is not the result of Neisseria gonorrhoeae or Trichomonas vaginalis. Any mucopurulent secretion noted from the endocervix that is yellow or green when viewed on a white cotton swab (positive swab test) is considered diagnostically positive. In addition, any induced endocervical bleeding that results when the swab is first introduced into the endocervical canal is also criteria for diagnosis of MPC. Laboratory tests must also show no evidence of either Neisseria gonorrhoeae or Trichomonas vaginalis (CDC, 1997a). Diagnostic Tests In 1995, a group of researchers from the CDC performed a national survey of STD testing sites across the United States. The purpose was to evaluate laboratory testing being used for sexually transmitted diseases. What Consuelo M. Beck-Sague (1996) and her colleagues discovered was 27 that, when asked what test, or tests, had been added within the past 2 years, nonculture tests for chlamydia were most often sited by survey respondents (34 of 81 [42%]). When asked to specify why that particular test had been recently included at their site, the most frequent response was that of available funding specifically targeted for chlamydia testing (25 of 81 [30.9%]), (Beck-Sague, et. al.). Of the sites using the nonculture chlamydia tests, 51.4% reported that they were using either enzyme immunoassays (ElAs), (55 of 254 [21.6%]), deoxyribonucleic acid probes (nucleic acid probes or DNA probes), (51 [20.1%]), direct flourescent antibody (DFA), (20 [7.9%]), or polymerase chain reaction (PCR), (2 [<1%]) tests (Beck-Segue, et. al., 1996). The remaining 126 of 254 (49.6%) of respondents failed to designate which nonculture test was utilized at their site. In the same study, when asked to list any test, or tests, that their site had ceased using within the past 2 years, the tests most often listed were the Gram stain or culture for gonorrhea (Beck-Sague, et. al., 1996). The number of facilities that performed stat Gram stains decreased from 170 in 1992 to 111 by the time of this study's 1994 survey (Beck-Sague, et. al.). When asked the reason for dropping that particular test, 91.9% of respondents cited their inability to comply with the more stringent requirements implemented by 28 the Clinical Laboratory Improvement Act as the reason for the discontinuation (Beck-Sague et. al.). Another test for chlamydia, which was not mentioned at all in the study by Beck-Segue et. al., (1996), is the ligase chain reaction (LOR) urine test. A study performed at Johns Hopkins University (Gaydos et. al., 1995), compared the sensitivity and specificity of the LCR to the EIA for chlamydia. Their results showed the LCR to be both highly sensitive (100% for males and 100% for females tested) and specific (99.6% for men and 98.5% for women) in its detection of chlamydia. By comparison, the EIA was found to be far less sensitive (10% for men and 15.2% for women); its specificity was also less, but not as dramatically ( 99.6% for men and 98.9% in women), (Gaydos et. al.). The LCR is still a relatively new test. It is a more expensive test than the other methods currently available and, therefore, not yet as widely used (Gaydos et. al.). To perform this test, urine specimens need to be centrifuged, then supernatant aspirated by pipet and a urine buffer added. This mixture is then heated to 100°C, cooled, frozen and shipped to a research laboratory. There, a probe amplification of the chlamydial DNA is performed by target-dependent ligation of complementary oligonucleotide probes by DNA ligase, after they have annealed to the gene target sequence. The specimens are then thermocycled after being added to hapten- 29 conjugated probes, buffer, and ligase, the thermostable enzyme. Once thermocycling is completed, amplified chlamydial DNA is detected by using an automated EIA test. Part of the problem in effectively combating chlamydia is the fact that there is no test for chlamydia which has been established as the “gold standard” (Schachter et. al., 1992). Newer nonculture tests for chlamydia have been developed with sensitivities and specificities exceeding those of the chlamydia culture. Schachter and colleagues concluded that due to the variety of tests that are available, and the characteristics of chlamydia, there is a need for a comprehensive control program that sets criteria for diagnosis and treatment of both symptomatic and asymptomatic individuals. Screening Characteristics Although high risk women are often screened through routine health care sought for birth control or illness, women with chlamydia are more likely to be asymptomatic (75%) than are men (50%) (CDC, 1997c). Conversely, CDC research found that although men may more often be symptomatic, they often have fewer screening opportunities. In one study of untreated, symptomatic heterosexual men, 45% spontaneously became asymptomatic within 1 month of testing (Rietmeijer, Judson, Boele Van Hensbroek, Ehret, & Douglas, 1991). This lead the researchers to conclude that, while there has 30 been less attention to screening and follow-up of men in the past, it may be worth increasing emphasis on men, as an indirect means of lowering the incidence of chlamydia infection in women. In a total of over 4500 clinic visits, Rietmeijer et. al. (1991) found that 42% of the men met the traditional treatment criteria for chlamydia. Twenty­ seven percent were diagnosed with NGU based upon the presence of > 4 PMN/HPF on Gram stain. There were 11% who were treated because of their diagnosis of gonorrhea and almost 4% who had had sexual contact with a female partner who had been diagnosed with, or was suspected of having, chlamydia. Men who remained asymptomatic comprised almost 41% of the total. The final 17% presented with complaints consistent with urethritis, but were not diagnosed or treated because they had not met any of the above criteria (Reitmeijer et. al., 1991). The results revealed that using the 1989 screening and testing recommendations of the CDC had failed to detect and promote treatment in 23.4% of the infected population. Table 1 contains the data from this Reitmeijer et. al. study. In an attempt to increase the sensitivity of the Gram stain as a screening tool, Rietmeijer et. al. (1991) used successively decreasing numbers of PMNs, down to a low of > 1 PMN/HPF, as the criteria for diagnosis of NGU. Even at that lowest level, they found that 45% of 31 Table 1 Chlamydial Infection in Heterosexual Men in a Study Reported by Rietmeijer et. al. (1991). Diagnostic Category Infected with Gonorrhea Total Tested Total Positive n (%) n (%) 516 (11-0) 62 (8-1) 1266 (27.0) 494 (64.9) 179 (3.8) 27 (3-5) 803 (17.1) 52 (6.8) Infected with NGU by > 4 PMN/HPF on Gram Stain Contact to Infected Partner Symptomatic but without Objective Evidence Asymptomatic 1917 (40.9) 126 (16.6) Total 4681 761 (100.0) (100.0) Note. NGU=Nongonococcal Urethritis, PMN=Polymorphonucleocyte, HPF=High Power Field. 32 infections still would have been missed by the Gram stain. Based upon this finding, these researchers concluded that the best method for detecting chlamydial infection and the need for treatment at the time of the initial clinic visit is not clear. They further indicated that additional research is needed to determine the most effective, expedient, and economic approach towards maximizing treatment at initial patient visits (Rietmeijer et. al., 1991). Another group of researchers did a comparison of overall STD testing results for men with and without presenting symptoms (Janier et. al., 1995). They utilized Gram stain, but with >5 PMN/HPF as the cut-off criteria for diagnosis of NGU (Table 2). In their conclusions, Janier et. al. (1995) emphasized the low sensitivity that a Gram stain smear had for indicating chlamydial infection in patients who reported no symptoms. They also pointed out that even in patients with symptoms, the sensitivity of the Gram stain was still only 86%. They concluded that every patient who presents with urethral symptoms should have a PGR for chlamydia performed, regardless of whether discharge is noted or PMNs are present on Gram stain. They noted that when discharge was present, Gram stain remained a valuable tool for the exclusion of N. gonorrhoeae. 33 Table 2 Gram Stain Urethral Smear Results in 219 Men With and Without Urethral Discharge from a Study Reported by Janier et. al. (1995). With Discharge (n=122) Pathogen Category Without Discharge (n=97) Smear + Smear - Smear+ Smear - n (%) n (%) n (%) n (%) Chlamydia 18 (19) 3 (11) 2 (7) 5 (7) Gonorrhea 23 (24) 2 (8) 0 (0) 0 (0) Ureaplasma 9 (9) 3 (11) 1 (4) 2 (3) Mycoplasma 25 (26) 4 (15) 4 (15) 4 (6) Trichomonas 3 (3) 0 (0) 0 (0) Indeterminate results 7 7 23 0 (0) 23 Patients with > 1 67 (70) 12 (46) 7 (26) 11 (16) Pathogens 9 (9) 6 (23) 7 (26) 23 (33) No Pathogen 20 (21) 8 (31) 13 (48) 36 (51) Total Patients 96 Pathogen Patients with Only Indeterminate 26 27 70 34 Treatment Characteristics. Once a patient has completed the screening and testing processes, the question of treatment arises. In a recent study, clinical records covering an 18 month period from over 35,000 patients of a county health department STD clinic were reexamined (Schwebke et. al., 1997). This study was one of the first to question how many patients with positive test results were actually treated. Treatment Before Test Results. The study by Schwebke et. al. (1997) revealed that only 1% of men who had positive cultures for gonorrhea had not been treated at their initial clinic visit, while the rate of untreated chlamydia at initial visit was 11%. For women, the rates were 12% and 44%, respectively. Of all the patients who reported no symptoms at their initial clinic visit, and left without receiving any kind of treatment, 12% had tests that showed they were infected with N. gonorrhoeae and 44% had tests showing they were infected with chlamydia. This rate was only 1% below the 45% failure rate of Gram stain screening that was found by Rietmeijer et. al. (1991). In the same study, Schwebke et. al. (1997) also discovered that screening detection rates for women were higher than for men. Patients’ charts from an STD clinic were reviewed for a designated 18 month interval. 35 The numbers of patients who tested positive for gonorrhea and chlamydia were compared to those who received presumptive treatment for these infections. They found that chlamydia went untreated at a much higher rate than did gonorrhea, and that women were more likely to go untreated than were men (Table 3). Treatment After Test Results. Once notified of infection, 20% of patients in the Schwebke et. al. (1997) study had not returned for treatment 30 days later. An additional 30% who returned to be treated did not do so until 2 or more weeks after their initial visit (Table 3). From an epidemiologic perspective, this 2 or more weeks of untreated time was viewed as a facilitator of disease spread due to the characteristics of the sexual practices among high risk populations. It allowed others to become infected by those who never returned for treatment, or during the 2-week interval between the visits of those who did return. With the discovery that high screening numbers did not assure treatment of patients who tested positive, Schwebke et. al. (1997) suggested that future emphasis needs to be placed on evaluating and identifying the best indicators for initial visit treatment. They further concluded that failing to treat patients deemed infected nullifies the value of the screening process. Based upon the constructs of epidemiology, Schwebke et. al. (1997) 36 Table 3 Patients With Positive Screening Tests Who Were Not Treated at Initial Visit, and Time Intervals Until Treatment Was Received, in a Study of 24,823 patients by Schwebke et. al. (1997). Patients No Treatment Treatment Within 30 Days Treatment In < 13 Days In 14-30 Days n / total (%) n / total (%) n / total (%) GC 95 / 530 (18) 286 / 530 (54) 149/530 (28) CT 125/634 (20) 286 / 634 (45) 223 / 634 (35) GC 20/34 (59) 8/34 (23) 6/34 (18) CT 11/43 (26) 20/43 (46) 12/43 (28) GC 115/564 (20) 294 / 564 (52) 155/564 (28) CT 136/677 (20) 306 / 677 (45) 235 / 677 (35) Females Males Totals Note. GC=gonorrhea, CT=chlamydia. 37 concluded that one method of increased treatment compliance among infected individuals may be through direct observation therapy, fashioned after the tuberculosis model for treatment, and by utilizing single-dose therapy. They further determined that the data from their study had important implications for future efforts to control and prevent sexually transmitted diseases. In the studies previously sited, Rietmeijer et. al. (1991) studied only Gram stain as it applied to men; Schwebke, et. al. (1997) found that screening cultures for both gonorrhea and chlamydia detected infection in women far more often than in men. Neither of these studies looked at Gram stain as a screening tool for women. This researcher found no data on women for comparison to the data Rietmeijer et. al. collected for men. If other indicators of chlamydial infection that occur simultaneously with positive Gram stain in women can be identified, they could facilitate future criteria for chlamydia treatment in the private health sector. Beck-Segue et. al. (1996) found that most primary care settings did not have the capability to maintain the requirements necessary for a laboratory certified to perform Gram stains. They also identified the fact that, while screening numbers and positive tests in private sector offices may be far fewer than in large public clinics, their role or value in the total picture of 38 combating STDs is still important. Nurse Practitioner Role As nurse practitioners (NPs) become more common in primary care offices, they will increasingly be in settings where on-site laboratory facilities may be less accessible than in the past. A national survey sought to examine NPs’ knowledge levels and treatment practices concerning chlamydia in their female patients (Alexander, Treiman, & Clarke, 1996). Of over 1600 questionnaires mailed, a response rate of 38% was obtained resulting in over 600 respondents. Of those, 49% identified their work site as a family planning or public health clinic. Overall, 88% of respondents had a scope of practice which included family planning, STDs, or gynecology. This study revealed that chlamydia was the most common STD identified in the tests of their patients. Fifty-five percent felt “very knowledgeable” and 40% “knowledgeable” about STDs, while 60% to 80% answered questions regarding chlamydia accurately. The only NP knowledge deficits identified by the study were related to appropriate screening and treatment of pregnant patients with chlamydia (Alexander et. al., 1996). When questioned about the type of diagnostic testing their facility utilized, 72% of the NPs reported that tests were performed at an off-site laboratory (Alexander et. al., 1996). The types of tests varied, with enzyme 39 immunoassay (EI A), direct flourescent antibody (DFA), nucleic acid hybridization (DNA), and culture all being named. Only 3% reported use of a rapid diagnostic test, which takes less than 30 minutes for on-site results. This study echoed previous ones by Schachter et. al. (1992) and Janier et. al. (1995) by declaring that “no single test has yet emerged as simple, noninvasive, inexpensive, specific and sensitive” (p. 51). The most frequently cited reason for delayed or absent treatment, was the lag time between the screening tests and the availability of the results (Alexander, et. al., 1996). The rates of presumptive treatment reported in the survey were compared to the current CDC guidelines (Table 4). Of all the survey treatment scenarios, patients were most likely to be presumptively treated for chlamydia (by 93% of the NPs) when they reported a sex partner infected with chlamydia (Alexander et. al., 1996). Conversely, they were least likely to be presumptively treated for chlamydia (by only 39% of the NPs) if they reported that a sex partner had acute urethral syndrome. Of all of the patients who did receive presumptive treatment reported in the survey, 24% of the nonpregnant and 34% of pregnant patients received either inappropriate or inadequate treatment according to the CDC guidelines. These data, obtained from NPs working predominantly (88%) in family planning, STD, and gynecology settings, reinforce the need for more 40 Table 4 Criteria For Presumptive Treatment for Chlamydia as Reported by Nurse Practitioners in a Survey Performed by Alexander et. al, (1996). Treatment Circumstance NPs (n=611) Patient says partner has CT* 93% Patient has signs and systems of PID* 88% Patient has MPC** 84% Patient says partner has NGU 72% Patient says partner has GC* 68% Patient has signs / symptoms of GC* 66% Wet prep shows high WBC count 61% Patient says partner has epididymitis 40% Patient has acute urethral syndrome** 39% Never presumptively treat 0% Notes. ‘Conditions which indicate presumptive treatment based upon CDC recommendations. **Conditions which may indicate presumptive treatment depending upon other risk factors, based upon CDC recommendations. CT=Chlamydia, GC=Gonorrhea, PID=Pelvic Inflammatory Disease, MPC=Mucopurulent Cervicitis, NGU=Nongonococcal Urethritis, NP=Nurse Practitioner, WBC=White Blood Cell. 41 specific guidelines and criteria regarding which patients to screen, what tests to use, and whom to treat. Is this study reflective of all NPs, or would the knowledge level and treatment deficits of NPs who work in family practice differ at all from those whose practice is primarily with women, reproduction, and public health? If NPs must play a role in the fight against chlamydia and its sequelae, what screening criteria, and testing data will best equip them? What role, if any, could use of Gram stain play in screening and presumptive treatment for chlamydia? Alexander et. al. (1996) concluded that nurse practitioners do need continuing education to perform adequate management of all sexually transmitted diseases within their patient populations. Summary The literature supports the application of the Epidemiologic Model with regard to chlamydial infection and barriers to its successful control. The “host” factors of variances between men and women, pregnant versus nonpregnant, symptomatic versus asymptomatic, have been examined. Characteristics of the “agent” that promote the of spread of chlamydia, while simultaneously making development of a single reliable test difficult, have also been reviewed. The “environment” has been viewed by factors such as a social climate of risk and noncompliance, a biologic risk from other STD 42 co-infections which may be present, or as physical risks where results of tests simply are not available on-site or in a timely manner. All of these epidemiologic factors have been reviewed in an attempt to learn what can be done differently, in a better attempt to control chlamydial infection. Gram stain has been identified as one component within the matrix of chlamydia control. In this review of literature, studies that identified the lack of current, consistent guidelines for screening and treatment of chlamydia, were examined. Various diagnostic testing methods, and comparisons of their effectiveness, have been mentioned. Screening methods and criteria for presumptive treatment, as well as lack of treatment and difficulty of patient compliance, have also been reviewed. The role of the nurse practitioner in the screening, testing, and treatment of chlamydia was discussed because their increasing numbers as primary care providers necessitate adequate knowledge for management and control of all sexually transmitted diseases, including chlamydia. Because of the holistic approach that nurse practitioners bring to primary care, they are well equipped to focus on the epidemiology of chlamydia control and may be able to serve as a bridge between the medical and public health communities. This could result in a positive impact on 43 chlamydia control efforts. 44 Chapter 3 Methodology If presumptive gonorrheal infection can be ruled out using a Gram stain, but white blood cells (WBCs) are still present, perhaps their presence is due to chlamydial infection. If their presence is a reliable positive predictor of patients infected with chlamydia, even in the absence of signs or symptoms, utilizing Gram stain would be a relatively simple, inexpensive, and immediate test for infection. These are all attributes of a desirable screening or diagnostic test for chlamydia. However, since the Gram stain may identify WBCs associated with conditions other than chlamydia, it is not a specific test. This chapter presents the hypothesis, operational definitions, research design, procedures, sample, informed consent, instrumentation, and data analysis that were utilized to execute this study. Hypothesis Patients with chlamydia infection will have white blood cells on Gram stain with or without clinical signs or symptoms. White blood cells on Gram stain, in patients with or without clinical signs or symptoms, will not empirically indicate chlamydia infection. Operational Definitions The following terms were operationally defined for this study. 45 1. White blood cells (WBCs) refer to polymorphonuclear (PMN) white blood cells, as identified by Gram stain laboratory testing. 2. Nongonococcal urethritis (NGU), a diagnosis for any male patient, is defined by a Gram stain smear without Gram positive diplococci indicative of gonorrhea that exhibits > 5 WBCs per oil immersion field (oim) (CDC, 1993b). 3. Mucopurulent cervicitis (MPC), a diagnosis for any female patient, is defined by a Gram stain smear without Gram positive diplococci indicative of gonorrhea that exhibits >10 WBC/oim (CDC, 1993b). 4. Chlamydial infection or chlamydia refers to genital Chlamydia trachamatis infection of adults and adolescents who have sought testing and treatment, and who were tested using transcription mediated amplification (TMA) obtained via male urethral or female cervical DNA probes. 5. Gram stain refers to either a male urethral or female cervical slide smear prepared as follows: After the slide is fixed by heating with a flame, it is flooded with a crystal violet solution which is left on for 1 minute. It is washed briefly with tap water, and drained. It is then flooded with iodine which is allowed to stand for 1 minute. It is then washed with tap water again. Next it is decolorized with a mixture of 95% ethyl alcohol and 5% acetone, until it runs clear. The slide is then counterstained with safranine 46 for 10 seconds, washed with tap water, and blotted dry (C. Cancilla, personal communication, November 12, 1997). Research Design This study was conducted utilizing a quantitative, matched groups design. It was implemented through a retrospective examination of clinical patients’ charts from the Erie County, PA Health Department’s sexually transmitted diseases (STD) clinic. Procedures Charts of patients seen in clinics conducted over a 6 month time period from July 1, 1997 through December 31, 1997, were reviewed. These months were chosen to coincide with the health department’s contracts for the chlamydia test method, and laboratory analysis of the tests, both of which began on July 1, 1997. Only those charts indicating that a nurse assigned to the STD division saw the patient and obtained the specimens fortesting, were considered. Any records indicating that nurses from another division obtained the clinical data were excluded due to what could be a lower level of experience and proficiency. The data to be examined were from patients who presented during sessions consistently staffed by one physician who had extensive experience M with STD patients. Additionally, the same laboratory technician was also present and had experience performing Gram stains. Sample The sample of 54 patients was derived from the population of patients who sought testing and treatment for STDs over a six month period in 1997, at the Erie County, PA Health Department. A second case control sample matched by race, gender, age, and clinic status as either a new patient or established patient, was chosen from the same population and same six month time period. Patients were included regardless of race, sex, religion, ethnicity, age, income, or health insurance status. Permission for use of the sample population data was obtained utilizing a written Access to Protected Data contract between the researcher and the Erie County Department of Public Health (Appendix A). It was completed according to the standards set by the Division of Health Statistics, Pennsylvania Department of Health, User’s Guide for Access to Protected Data (Appendix B). All patients signed a dated written consent for testing and treatment (Appendix C). The patients were referred to by an assigned clinic number whenever addressed outside of a clinic room. They were assured of confidentiality and were not required to produce any type of identification. No billing was conducted, so no insurance cards or social security information was 48 obtained. Although a patient’s address and phone number were recorded, if patients requested no calls or mail, they were not contacted unless there was an emergency. Prior to leaving the clinic, patients were issued a code number to use if they called the clinic in regards to their visit or to obtain any test results. If they called without the number, no information was given until they appeared in person and produced identification. This prevented parents, sex partners, spouses, friends, or any other medical establishment from accessing information without written consent. Medical information from charts was never sent over a FAX, unless a clear threat to the patient’s life or well-being had been established and the patient’s permission to release information had been received. From the population of patients as described, seen within the designated time period for this study, two matched sample groups were chosen for inclusion. The first group was comprised of any patient who tested positive for chlamydia. The second was comprised of patients who tested negative for chlamydia. The groups were matched for age, gender, race, and whether they were first time attenders to the STD clinic, or had been seen on previous visits in the past. 49 Informed Consent Due to the security, anonymity, and confidentiality regarding all patient clinical records, any follow-up contact with patients regarding the information reviewed for this study was prohibited by the policies and procedures of the health department’s medical division. Because individuals whose chart information was utilized were never identified, informed consents from the patients whose records were reviewed, were not required fortheir inclusion in the study. The Access to Protected Data included consent to utilize the records in a confidential manner on-site, with the agreement that no identifying information be recorded or utilized in the study. Instrumentation In accordance with the study design a spreadsheet was used to record the data from each patient’s chart (Appendix D). The following data were collected: 1. Demographic Characteristics . The age, gender, race, and the patient’s status as a “first visit” or “established patient” were recorded. 2. Independent Variables. Several independent variables were recorded and included: a. Was there a patient complaint of urethral or vaginal discharge? b. Were any signs of urethral or cervical discharge recorded by the 50 nurse who performed the patient’s examination and testing? c. Was urethral or cervical bleeding recorded by the nurse when the test specimen was obtained? d. The results of the Gram stain to include: 1) Gram-positive diplococci, indicating gonorrheal infection, 2) WBCs sufficient to meet criteria for diagnosis of NGU or MPC, 3) the presence of both Gram-positive diplococci and WBCs sufficient to meet the criteria for diagnosis of NGU or MPC and gonorrhea. e. Wet mount results (female patients only), for detection of: 1) yeast, 2) Trichomonas, 3) clue cells indicative of bacterial vaginosis. f. Any medications prescribed for the presumptive treatment of chlamydia on the date of the clinic visit. g. Whether the patient returned for chlamydia treatment at a later date. h. The nurse who performed the examination and testing. 3. Dependent Variable Results of any laboratory tests sent to an off-site lab for Transcription Mediated Amplification (TMA) chlamydia and gonorrhea testing: a. TMA/DNA probe gonorrhea result. b. TMA/DNA probe chlamydia result. 51 Data Analysis The data from each patient’s chart were tabulated utilizing the Statistical Package for Social Scientists (SPSS) for Windows Base System User’s Guide Release 6.0 version. They were statistically analyzed using frequency tables, and T-tests for continuous variables. Pearson uncorrected chi square analysis and Fisher’s two-tailed test were used for categorical variables. Differences between groups were considered statistically significant if P< 0.05. These statistical analyses were then reviewed as a basis for either accepting or rejecting the hypothesis of the study. Summary This chapter has outlined the methods of the study. The hypothesis was defined and the operational definitions, the research design, and procedures to be used in the testing of the hypothesis were detailed. The sample was discussed, as was the instrumentation used for data collection, and the statistical analysis of the data. 52 Chapter 4 Results In this chapter, the statistical analysis of the data collected from 54 patient charts are discussed. It includes comparisons of clinical indicators and Gram stain results to DNA probe results. Additionally, a comparison of gonorrhea and chlamydia results are reviewed. Demographic Data There were 22 (40.7%) white and 32 (59.3%) black patients included in the study. Thirty-six (66.7%) were male and 18 (33.3%) were female. Patients who had been to the clinic on at least one other occasion numbered 12 (22.2%), while those who were there for the first time were 42 (77.8%). The mean age of the clients was 19.6 years, with a range from 16 to 30 years of age. However, 36 (66.6%) of the 54 patients included in the study were aged 16 to 19 years (Table 5). Clinical Indicators and DNA Probe Chlamydia Results The results of the Gram stains for WBCs and the DNA probes for chlamydia did show a statistically significant relationship (P=0.00014). These results and those of the other clinical indicators examined, and their corresponding DNA test results are shown in Table 6. Thirty-seven (69%) of the 54 patients were diagnosed with either nonspecific cervicitis (NSC) or 53 Table 5 Demographic Data for Study Sample Groups Patients Chlamydia Positive Chlamydia Negative n=27 n=27 18 18 9 9 White 11 11 Black 16 16 Age 16-19 18 18 Age 20 - 30 8 8 Age > 30 1 1 21 21 6 6 Males Females First patient visit Established patient 54 Table 6 DNA Probe Chlamydia Results and Results of Other Clinical Indicators in Patients From the STD Clinic in This Study. DNA Probe Chlamydia + DNA Probe Chlamydia - P (chi-squared n=27 No.(%) n=27 No.(%) Patients Yes No Yes No Totals 27 0 27 0 25(93) 2(7) 12(44) 15(55) P=0.00014 Patient Reports Discharge 10(37) 17(63) 10(37) 17(63) P=1.0 NS Gram+ Diplococci on GS 5(19) 22(81) 5(19) 22(81) P=1.0 NS 14(52) 13(48) P=0.09087 NS 6(22) 21(78) P=0.75026 NS test)** WBCs on GS Diagnosed as NSC/NGU Nurse Reported Discharge Observed on Exam 20(74) 7(26) 20(74) DNA+ for Gonorrhea 7(26) First Visit to the Clinic 20(74) 7(26) 22(81) 5(19) P=0.51269 NS Note. DNA Deoxyribonucleic acid, GS=Gram stain, NSC=Nonspecific cervicitis, NGU=Nongonococcal urethritis, WBCs=White blood cells. **P=The probability as computed by using the Pearson chi square two- tailed level of significance value < 0.05. 55 nongonococcal urethritis (NGU) based upon their Gram stain results. All of them were presumptively treated for chlamydia except for one, whose results were inadvertently misinterpreted by the physician. One patient was not diagnosed with NSC or NGU but was treated presumptively for chlamydia based upon sexual contact to a partner infected with chlamydia. Ten patients (19%) had Gram-positive diplococci present on the Gram stain and were presumptively diagnosed with gonorrhea as a result. All ten of these also had white blood cells (WBCs) sufficient on Gram stain to be diagnosed with either NSC or NGU. They were treated for chlamydia based upon either of those criteria as, designated by the Centers for Disease Control and Prevention treatment guidelines (CDC, 1993b). When the laboratory results of the DNA probes were received they revealed that 13 patients (24%) had been treated presumptively for chlamydia who tested negative for chlamydia by DNA probe. Conversely, only two patients (<1%) without sufficient WBCs on Gram stain had positive chlamydia results. Of the ten patients diagnosed with gonorrhea based upon the Gram stain, five (9%) had DNA probe results positive for gonorrhea, while the remaining five had negative results. Two patients who had no Gram-positive diplococci, but did have WBCs on Gram stain, had DNA probe results positive for both gonorrhea and 56 chlamydia. Two patients had WBCs and Trichomonas when initially seen but were also DNA-positive for chlamydia. One patient had yeast, Gram-positive diplococci, and WBCs all present when first seen with a DNA probe positive for both chlamydia and gonorrhea. Gram Stain Versus Other Clinical Indicators Comparing other data to Gram stain as indicators for chlamydia infection revealed that 20 (37%) of the 54 patients complained of either a vaginal or urethral discharge. Of these, ten (19%) were chlamydia-positive and the other ten were chlamydia-negative (P=1.0), from study totals of 27 chlamydia-positive and 27 chlamydia-negative patients. When clinical data recorded by the nurses who performed the physical examinations and testing were compared, they reported that discharge was observed from 19 (35%) of the patients who also exhibited WBCs on gram stain and were subsequently DNA-positive for chlamydia. One patient who had discharge recorded, as observed by the nurse who performed the exam, did not exhibit WBCs on the Gram stain, but had DNA results positive for chlamydia. The nurses were able to identify 20 of 27 (74%) of the patients infected with chlamydia in comparison to the Gram stain identifying 25 of 27 ([93%] P=0.09). Where the WBCs on Gram stain indicated presumptive treatment of chlamydia in 12 of 27 (44%) patients who tested DNA probe negative, the 57 nurses observed urethral or cervical discharge in 14 of 27 (52%) patients who tested DNA probe chlamydia negative. In patients not observed to have any discharge the nurses missed 7 of 27 (26%) patients who tested DNA-positive, while the absence of WBCs on Gram stain missed just 2 of 27 (7%) positive patients. Gonorrhea Versus Chlamydia Results Overall, there were 8 patients the nurses reported as having no discharge who had WBCs on the Gram stain. Six of these were DNApositive for chlamydia and 2 were DNA-positive for gonorrhea. Both of the patients reported by the nurses as having no discharge, who later were confirmed to have gonorrhea by the DNA probe, had also both lacked Gram-positive diplococci on the Gram stain. In contrast to the two patients who were chlamydia-positive but exhibited no WBCs on the Gram stain, all ten of the patients who tested positive for gonorrhea also were positive for WBCs on the Gram stain, even in the two cases where the Gram-positive diplococci were absent. None of the other clinical indicators were statistically significant in this study besides the relationship between Gram stain WBCs and DNA probe chlamydia results. Due to possible interrelations between the other clinical factors there may be other relationships present that, if isolated, would be 58 clinically and statistically significant to chlamydia infection. 59 Chapter 5 Discussion The relationship between the presence of white blood cells (WBCs) on Gram stain and chlamydia infection was studied in 54 patients who attended a public health clinic for sexually transmitted diseases (STDs). Other clinical indicators were also examined for their relationship to chlamydia. Although a relationship between the Gram stain and DNA chlamydia results was found, the presence of multiple other infections within both the sample groups made other relationships difficult to isolate. This chapter will review conclusions that were drawn and recommendations for future studies that may provide a clearer look at other clinical indicators for chlamydia. Conclusions A Gram stain with an absence of WBCs had a higher predictive value of a DNA chlamydia-negative test than did a Gram stain with the presence of WBCs of a DNA chlamydia-positive test. This supports the research hypothesis being studied. The Centers for Disease Control and Prevention give criteria for presumptive treatment for chlamydia (CDC 1993b). The data of this study support the literature with the conclusion that there is no clear indicator concerning which patients may be infected with chlamydia, and 60 which ones are not. Two patients infected with chlamydia left the clinic without medicine to treat it, based upon their Gram stain results. Conversely, there were twelve patients given medication for chlamydia based on their Gram stains, who didn’t need it because they were actually chlamydia- negative. When compared to the other indicators for infection that were collected, no others were more accurate than the WBCs on Gram stain in predicting which patients might be infected. Urethral or cervical discharge observed by the examining nurse was the closest, but 14 patients (26%) with observed discharge tested DNA-negative for chlamydia, and seven patients (13%) without observed discharge tested DNA-positive for chlamydia. Therefore, the nurses’ observations were not consistent as positive predictors of chlamydial infection. However, of the 54 patient charts reviewed, there were only three patients with discharge observed by the nurse who did not test positive for some type of genital infection and, if studied further may hold statistical significance. One of these three had already tested positive for chlamydia at another facility, and one had a sexual partner infected with gonorrhea. Since all ten patients who were DNA-positive for gonorrhea had WBCs on Gram stain (including the two who lacked any Gram-positive 61 diplococci), in this study the WBCs had a higher positive predictive value for gonorrheal infection than did the presence of Gram-positive diplococci, even though preliminary diagnosis of gonorrhea was based upon the diplococci, not the WBCs being present. Since one-half of those patients with gonorrhea also had chlamydia, it isn’t clear which infection was more or less directly associated with the WBCs present. In the study by Janier et. al. (1995), urethral smears had a sensitivity of 86% for detection of chlamydia in patients with discharge. Comparatively, the data collected in this study had a sensitivity of 68%. The research by Janier et. al. and others that studied the indications of WBCs on Gram stain, have only looked at men. This study included both men and women. It is not clear what differences this may have made in the overall results obtained, but since women with yeast, Trichomonas, and gonorrhea were all identified and any of the three can cause discharge, part of the answer may lie here. Recommendations Due to the small sample size, generalizations cannot be readily made from the data which were obtained. Some interesting questions for future research, however, are raised. Although this study sought to examine testing for chlamydia, one of the most interesting findings was that all patients who tested DNA-positive for gonorrhea had WBCs present on the Gram stain, 62 while two were lacking the Gram-positive diplococci traditionally used as the Gram stain criteria for preliminary gonorrhea diagnosis. A study comparing the WBCs and Gram-positive diplococci for gonorrhea infection is a possible indication for future research. Additionally, while the nurses’ reports of discharge in patients was not as reliable as the Gram stain in predicting chlamydial infection, it was clearly more predictable than the report of discharge by the patients. Due to the multiple possible pathogens with which patients may be infected, it is likely that some patients the nurses reported as having discharge may well have had pathogens other than chlamydia as the source. A future study which used a sample population of patients found to be infected with chlamydia only may be a more specific method of assessing the value of both WBCs on Gram stain, and nurses reports of discharge, as chlamydial indicators. Due to the physiological differences between men and women, and the effects these differences may play in the biological manifestations of infection, studying the relationship of WBCs and discharge to chlamydial infection may be better carried out in studies that examine just men or just women. This study does show that in the interests of public health, and the control of the spread of chlamydia, the presence of WBCs on the Gram stain, and the presence of either urethral or cervical discharge, are both strong 63 enough indicators of infection to treat the patient presumptively. In a private practice where Gram stain is likely to be unavailable, signs of discharge indicative of infection warrant treatment. If wet mount for females is available and is free from Trichomonas, yeast, and clue cells, the presence of WBCs may be an indicator of either a chlamydial or gonorrhea infection. Research to correlate WBCs from Gram stain to wet mount could be valuable in assessing the wet mount as a tool for detection of these two infections. With medications such as azithromycin now available for single-dose therapy for both gonorrhea and chlamydia, and with the health maintenance organizations (HMOs) putting pressure on primary care providers to reduce costs, treating patients who have observable discharge or who exhibit signs of infection using a wet mount, may well be more efficacious than the cost of DNA tests. Using a 2 gram dose of azithromycin would effectively treat both gonorrhea and chlamydia in a single dose not only eliminating the cost of the DNA testing, but also the wait which often results in treatment failure, or the opportunity for disease spread in the interim. 64 References Alexander, L. L., Treiman, K., & Clarke, P. (1996). A national survey of nurse practitioner chlamydia knowledge and treatment practices of female patients. The Nurse Practitioner, 21(5), 48:51:52:54. Beck-Sague, C. M., Cordts, J. R., Brown, K., Larsen, S. A., Black, C. M., Knapp, J. S., Ridderhof, J. C., Barnes, F. G., & Morse, S. A. (1996). Laboratory diagnosis of sexually transmitted diseases in facilities within the United States. Sexually Transmitted Diseases, 23, 342-349. Carr, P. L., Freund, K. M., & Somani, S. (1995). The medical care of women. Philadelphia: W. B. Saunders Company. Centers for Disease Control and Prevention (1993a). Recommendations for the prevention and management of Chlamydia trachamatis infections. Morbidity and Mortality Weekly Review 42 (RR-12), 1- 41. Centers for Disease Control and Prevention (1993b). 1993 Sexually transmitted diseases treatment guidelines. Morbidity and Mortality Weekly Report 42 (RR-14), 1-102. Centers for Disease Control and Prevention (1996a). What we have learned...1990-1995, clinic flow and utilization. Atlanta: Author. Centers for Disease Control and Prevention (1996b). 1996 (October) annual report. Atlanta: Author. 65 Centers for Disease Control and Prevention (1997a). Case definitions for infectious conditions under public health surveillance. Morbidity and Mortality Weekly Review 46 (RR-10), 1 -38. Centers for Disease Control and Prevention (1997c). Chlamydia screening and treatment programs for young women. Atlanta: Author. Centers for Disease Control and Prevention (1997d). 1997 (October) annual report. Atlanta: Author. Centers for Disease Control and Prevention (1997e). Provisional cases of selected notifiable diseases, United States. Morbidity and Mortality Weekly Report 46 (40), 954-955. Chinn, P. L., & Kramer, M. K. (1995). Theory and nursing: A systematic approach (4lh ed.). St. Louis: Mosby-Year Book, Inc. Clark, M. J. (1992). Nursing in the community. Norwalk, CT: Appleton & Lange. Commonwealth of Pennsylvania Department of Health (1970). History of V. D. (Schwartz, W. F., H502.510P, 4/70). Atlanta, GA: Communicable Disease Center, U. S. Department of Health, Education and Welfare. Eliot, T. S. (1943). Four guartets. New York: Harcourt, Brace & World, Inc. Eng, T. R., & Butler, W. T. (Eds.) (1997). The hidden epidemic: 66 Confronting sexually transmitted diseases. Washington, DC: National Academy Press. Erie County Department of Health (1997). Communicable disease statistics. Erie, PA: Author. Fischbach, F. (1988). A manual of laboratory diagnostic tests. Philadelphia: J. B. Lippincott Company. Gaydos, C. A., Ngeow, Y. F., Lee, H. H., Canavaggio, M., Welsh, L. E., Johanson, J., & Quinn, T. C. (1996). Urine as a diagnostic specimen for the detection of Chlamydia trachamatis in Malaysia by ligase chain reaction. Sexually Transmitted Diseases, 23, 402-406. Groer, M. W., & Shekleton, M. E. (1989). Basic pathophysiology: A holistic approach. St. Louis: The C. V. Mosby company. Hill, C. S. (1996, November). Gen-Probe transcription-mediated amplification: System principles. San Diego: Gen-Probe Incorporated. Hippocrates (1972). The genuine works of Hippocrates (F. Adams LL. D., Surgeon, Trans.). Huntington, NY: Robert E. Krieger Publishing Company. (Original work written -460 B. C.). Janier, M., Lassau, F., Casin, I., Grillot, P., Scieux, C., Zavaro, A., Chastang, C., Bianchi, A., & Morel, P. (1995). Male urethritis with and without discharge: A clinical microbiological study. Sexually Transmitted Diseases, 22, 244-252. 67 Keeling, A. W. (1996). Care versus cure-examining the dichotomy through a historical lens. Journal of Professional Nursing, 12, 131. Laboratory Corporation of America (1997-1998). Director/ of services & interpretive guide. Burlington, NC: Author. Lamm, R. D. (1990). The ten commandments of health care. In P. R. Lee, & C. L. Estes (Eds.), The nation's health (3rd ed., pp. 124-133). Boston: Jones and Bartlett Publishers. Leavell, H. R., & Clark, E. G. (1979). Preventive medicine for the doctor in his community, an epidemiologic approach (3rd ed.). Huntington, NY: Robert E. Krieger Publishing Company, Inc. Lennette, E. H. (Ed.). (1980). Manual of clinical microbiology (3rd, ed.). Washington, DC: American Society for Microbiology. Mausner, J. S., & Bahn, A. K., (1974). Epidemiology: An introductory text. Philadelphia: W. B. Saunders Company. Phillips, R. S. (Ed.). (1986). Funk & Wagnells new encyclopedia (vol. 11). New York: Funk & Wagnells Publishing. Rietmeijer, C. A. M., Judson, F. N., Boele Van Hensbroek, M., Ehret, J. M., & Douglas, J. M. (1991). Unsuspected Chlamydia trachamatis infection in heterosexual men attending a sexually transmitted disease clinic: Evaluation of risk factors and screening methods. Sexually Transmitted Diseases, 18, 28-35. 68 Schachter, J., Stamm, W. E„ Chernesky, M. A., Hook, E. W., Jones, R. B„ Judson, F. N., Kellogg, J. A., LeBar, B„ Per-Anders, M., McCormack, W. M., Quinn, T. C., Ridgway, G. L, & Taylor-Robinson, D. (1992). Nonculture tests for genital tract chlamydial infection. Sexually Transmitted Diseases, 20, 243-244. Schwebke, J. R., Sadler, R., Sutton, J. M., & Hook, E. W. (1997). Positive screening tests for gonorrhea and chlamydial infection fail to lead consistently to treatment of patients attending a sexually transmitted disease clinic. Sexually Transmitted Diseases, 24,181-184. U. S. Department of Health and Human Services, Public Health Services (1991). Healthy people 2000: National health promotion and disease prevention objectives. Washington, DC: Public Health Service, 1991: 496-510. (Publication No. PHS-91-50212.) U. S Department of Health and Human Services Staff, Office of Disease Prevention and Health Promotion (1994). Clinician's handbook of preventive services: Put Prevention Into Practice, McLean, VA: International Medical Publishing. 69 Appendixes Appendix A 70 OOOO1 APPLICATION FOR ACCESS TO PROTECTED DATA ERIE COUNTY DEPARTMENT OF HEALTH 606 WEST SECOND STREET ERIE, PA 16507 (814) 451-6700 January, 1998 71 app^tiT^ USER’S GU'DEF°R ACCESS TO PROTECTED DATA before completing this I. ORGANIZATION ORT INDIVIDUAL REQUESTING ACCESS A. Project Directon B. Title: C. Organization: D. Street Address or P.O. Box: E. City, State, Zip Code: F. Telephone: (Area code) G. H. n. Other persons who should be contracted if more information is needed: 1. Name: 2. Telephone: 3. Address (if different than above): 1. Name: 2. Telephone: 3. Address (if different than above): Name and address of sponsor(s) or funding organization(s) for this project: TITLE OF STUDY OR PROJECT 72 in. OTHER ORGANIZATIONS PARTICIPATING IN THIS STUDY OR PROJECT List the names of organizations and/or individuals who will obtain identifiable information or individ­ ual case record data from Erie County Department of Health files and describe their roles in this study Include consultants, outside nosologists, contractors, data processing vendors, subcontractors, and sponsoring or participat­ ing agencies or organizations. A “Supplemental Assurances Form” (see pages 12-15) must be com­ pleted by EACH organization (or individual) listed below and must be signed by responsible officials of that organization. The completed forms must be submined as an attachment(s) to this application form. IV. INSTITUTIONAL REVIEW BOARD FOR THE PROTECTION OF HUMAN SUBJECTS Has this research project been reviewed and approved by an Institutional Review Board (IRB) for the Protection of Human Subjects? (An IRB approval is required if this study or project involved any “followback” activities to families, next-of-kin, or the study subject based on information provided by Erie County Department of Health records.) YES: NO: V. Give the name of the review board and date of approval below and attach a copy of the approval to this application. Indicate reason. SUMMARY OF STUDY PROTOCOL OR PROJECT ACTTVITIES You may append a copy of your complete study protocol (or selected sections) to this application; how­ ever, the abstract that you provide in response to these questions should be self-contained so that it can serve as a complete and accurate description of the project though separate from any appended document. Include the following information (A-F) in the description of your research plan or project activities. It is understood that some requestors might only be indirectly involved in research or statistical activities (e.g., preparing and maintaining data files to be used in the research efforts of other organiza­ tions) or for government agency projects. If any of these situations apply, you should first describe your own activities and then indicate how the identifiable data released to you will be provided to and used by other organizations. IN RESPONDING TO THE FOLLOWING QUESTIONS, BE AS CLEAR AND AS SUCCINCT AS POSSIBLE USING THE SPACE AVAILABLE. If you require additional space for answers, insert a separate page(s) and number each answer. 73 A. Describe the health or medical problem addressed by your study or activities. B. List the primary objectives, and include a description of the hypotheses to be tested. C. Summarize the project’s data collection methods, indicating specific followback procedures, if they •'■oply. D. Summarize the project’s analysis, indicating how the data will be used. Describe any data files that will be linked with the data provided and specify the source of these data files. F. In what form and to whom will the results of your study or activities be released? 74 VI. EMPLOYEE REGISTRY DESCRIPTION This section (pages 5-6) should be completed only if you are planning to include Erie County Department of Health records in an Employee Registry. The following information is required to provide the Department of Health with assurances that Erie County Department of Health records included in an Employee Registry will be used solely for statistical purposes in medical or health research. A. What is the date that the Registry was founded? B. What is the purpose of the Registry? C. What is the eligibility criteria for including persons in the Registry? D. Will ±e records be flagged to identify them as Erie County Department of Health records? YES E. Will the records be stored separately from the administrative records? YES F. NO NO Is your organization OSHA regulated? YES NO If yes, can you guarantee that Erie County Department of Health death records will not be released to OSHA? YES NO 75 G. List below each study which used records from the Employee Registry. All current studies should be included as well as anticipated studies. A summary protocol for each study listed above must be attached to this application form. The summary should include the following information. 1. Title of Study. 2. Description of the health or medical problem addressed by your study. 3. List of the primary study objectives and a description of the hypotheses to be tested. 4. Summary of the project’s data collection methods, indicating specific followback procedures, if they apply. Refer to the User’s Guide for the guidelines which must be followed when using Erie County Department of Health records for followback activities. 5. Summary of the project’s analysis and how the data will be used. 6. Description of any data files that will be linked with the data provided and the sources of these data files. 7. The form in which the results of the study will be released. Copies of any reports that are published externally should be forwarded to the Erie County Department of Health. If the complete protocol is sent in lieu of this summary, the sections from the protocol which contain the above requested information should be highlighted. If Erie County Department of Health records are released for inclusion in your Employee Registry, summary protocols of any future studies (which are not included in this application) must be forwarded to the Erie County Department of Health for written approval prior to using any Erie County Department of Health records in the study. Amy changes to study protocols, particularly with respect to followback and additional uses of the data, must be submitted to the Erie County Department of Health. 76 VIH. RECORDS AND/OR IDENTIFIABLE DATA REQUIRED A. In the matrix below, indicate the type and form of records, identifiable data, and/or individual case record data requested. Provide an “X” in EACH box that is applicable: Review of Records Copies of Records Facsimiles/ Computer Listings Computer Data Tapes Diskettes Death Records Birth Records Fetal Death Records Cancer Records Other (Specify) B. Complete this section only if you are requesting review of records or copies ofrecords. 1. How many names do you expect to submit to the Department? 2. Is year of birth, death and/or date of diagnosis known for each name? YES NO If yes, please specify range of years involved: 3. How many future searches do you expect to request? 4. Name the organization(s), including your own, which will be requesting review of records or copies of records (itemize your responses if more than one organization will be involved). 77 C. vm. Complete this section only if you are requesting cancer facsimiles, computer listings, or computer data tapes. 1. Please list below the specific data items that you expect to obtain from each data file and/or those items that are specifically needed for your study. 2. How many future requests for this data do you expect to make? MAINTAINING THE CONFIDENTIALITY AND SECURITY OF IDENTIFIABLE DATA A. How will you maintain the confidentiality and security of identifiable data obtained from Department of Health records? (Identifiable data refers to any information which could permit the identification of any individual. This is not only name and address, but also individual case record data where other demographic items such as age, sex, race, and place of residence could possibly be used to identify subjects.) B. Disposition of identifiable data: 1. How long will you store copies of records or other identifiable data? 2. How will you dispose of copies of records or other identifiable data? 3. If there are no plans to dispose of some or all of the identifiable data, please explain why. 78 C. Approximate date of study completion: D. Will you require followback investigations based on information provided by Erie County Department of Health records to obtain additional information from decedent’s next-of-kin, study subjects, physicians, hospitals, and/or other individuals or facilitates mentioned in the records? YES NO If YES, briefly describe the following: 1. Types of followback respondents to be contacted. (If the answer to this question includes families, next-of-kin, or the study subject, please answer the following questions 2 and 3.) 2. Information to be obtained from respondents. (A copy of the survey form or ques­ tionnaire must also be attached and labelled appropriately). 3. Methods to be used in conducting such investigations. (A copy of consent form and initial contact letter to be mailed to followback individual must also be attached and labelled appropriately.) 19 E. Will any of the identifiable data obtained from the records and/or followback investigations be used as a basis for legal, administrative, or other actions which may directly affect particular individuals as a result of their specific identification in this project? YES NO If YES, Please explain. F. Will the identifiable data obtained from the records or followback investigations be used either directly or indirectly for any project or purpose other than the one described in Pan V? YES NO If YES, briefly describe the other research project(s) or purpose(s) for which the data will be used. A separate application form must be submitted for each project which will be using protected data obtained from Erie County Department of Health records. 80 IX. applicant assurances The undersigned hereby agrees to the following terms and conditions related to this application and to the use of information obtained from the Erie County Department of Health. A. The identifiable data obtained following written approval from the Department of Health shall be used only for the study proposed and the purposes described in the “Summary of Study Protocol or Project Activities” (Part V) and in the “Employee Registry Description” (Part VI). Use of the information for a project or purpose other than that described in Parts V and VI shall not be undertaken unless a separate application form for the subsequent project has been submitted to, and approved by, the Erie County Department of Health. B. No individually identifiable data shall be released without prior written approval by the Erie County Department of Health. c. If data extracted from Erie County Department of Health records are used in any publication, the following statement must be included in such publication or any other release of the data: These data were supplied by the Erie County Department of Health, Erie County Department of Health, Harrisburg, Erie County Department of Health. The Erie County Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions. A copy of any published materials or study results should be made available to the Erie County Department of Health upon request. D. I have thoroughly reviewed the contents of the User's Guide for Access to Protected Data dated October, 1996, which are incorporated herein by reference, and I shall adhere to the guidelines set forth therein. E. All statements entered in this application are true, complete, and correct to the best of my knowledge and belief. Project Director’s Name Project Director’s Title Organization Signature Date 81 ATTACHMENT A ERIE COUNTY DEPARTMENT OF HEALTH APPLICATION FOR ACCESS TO PROTECTED DATA SUPPLEMENTAL ASSURANCES FORM A separate Supplemental Assurances Form (pages 12-15) must be completed and signed by EACH organization listed on page 3 of the application form as participating in this study. The Supplemental Assurances Form(s) must then be submitted as an attachment to the application form. Additional copies of pages 12-15 may be made as required. Name: Title: Organization: Street Address or P.O. Box: City, State, Zip Code: Telephone: (area code) A. How will you maintain the confidentiality and security of identifiable data obtained from the Department of Health records? (Identifiable data refers to any information which could permit the identification of any individual. This is not only name and address, but also individual case record data where other demographic items such as age, sex, race, and place of residence could possible be used to identify subjects.) B. Disposition of identifiable data: 1. How long will you store copies of records or other identifiable data? 2. How sill you dispose of copies of records or other identifiable data? 3. If there are no plans to dispose of some or all of the identifiable data, please explain why. 82 C. Approximate date of study completion: D. Will you require followback investigations to obtain additional information from decedent’s next-of-kin, study subjects, physicians, hospitals, and/or other individuals or facilities mentioned on the records? YES NO If YES, briefly describe the following: 1. Types of followback respondents to be contacted. (If the answer to this question includes families, next-of-kin, or the study subject, please answer the following questions 2 and 3.) 2. Information to be obtained from respondents. (A copy of the survey form or questionnaire must also be attached and labelled appropriately.) 3. Methods to be used in conducting such investigations. (A copy of consent form and initial contact letter to be mailed to followback individual must also be attached and labelled appropriately.) 83 E. Will any of the identifiable data obtained from the records and/or followback investigations be used as a basis for legal, administrative, or other actions which may directly affect particular individuals as a result of their specific identification in this project? YES NO If YES, please explain. F. Will the identifiable data obtained from the records or followback investigations be used either directly or indirectly for any project or purpose other than ;the one described in Part V of the Application for Access to protected Data? YES NO If YES, briefly describe the other research project(s) or purpose(s) for which the data will be used. A separate application form must be submitted for each project which will be using protected data obtained from Erie County Department of Health records. 84 APPLICANT ASSURANCES The undersigned hereby agrees to the following terms and conditions related to this application and to the use of information obtained from ±e Erie County Department of Health. A. The identifiable data obtained following written approval from the Department of Health shall be used only for the study proposed and the purposed described in the "Summary of Study Protocol or Project Activities” and “Em­ ployee Registry Description: (Parts V and VI of the Application for Access to Protected Data). Use of the infor­ mation for a project or purpose other than that described in Parts V and VI shall not be undertaken unless a separat application form for the subsequent project has been submitted to, and approved by, the Erie County Department or Health Department of Health. B. No individually identifiable data shall be released without prior written approval by the Erie County Department or Health. C. If data extracted from Erie County Department of Health records are used in any publication, the following statement must be included in such publication or any other release of the data: These data were supplied by the Erie County Department of Health, Erie County Department of Health, Harrisburg, Erie County Department of Health. The Erie County Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions. A copy of any published materials or study results should be made available to the Erie County Department of Health upon request. D. I have thoroughly reviewed the contents of the User’s Guide for Access to Protected Data dated October, 1996, which are incorporated herein by reference, and I shall adhere to the guidelines set forth therein. E. All the statements entered in this application are true, complete, and correct to the best of my knowledge and belief. Name Title Organization Signature applic-doc l/!3/98/»k Date 85 COUNTY OF ERIE Department of Health JuChn M. Lyncn Ccxjnty Executtve 606 West Second Street Erie. Pennsytvcnia 16507 814/451-6700 Fax: 814/451-6767 Jo*eon IrzyoruJa Ontcror ERIE COUNTY BOARD Of HEALTH SnxwyJ-Zogor>d V*nc*nri_ Jonco. D.O. ^0*00 A Noowomy. M.O. 0. Zum Bonrra K. Book* Application Review Committee The following committee members have reviewed and approved the contents of the attached application. The committee reviewed the application for the proper and secure use of identifiable data and assure proper disposal of data as stated in the proposal at the end of the study . No identifiable data will be released. The principal investigator has signed the applicant assurance statement of the application. The Erie County Deparment of Health and Review Committee specifically disclaim responsibility for any analyses, interpretations or conclusions. A copy of any published material or study results will be made available to the Erie County Department of Heal±. The review committee and principal investigator has reviewed the Users Guide for Access to Protected Data which are incorporated herein by reference, and shall adhere to the guidelines set forth therein. Title of Study:. Principal Investigator:. Signature: Reason for Study:. Date of Review by Committee:. .* Approved by: Signature t Date / Charlotte Berringer, Director Personal Health Services Erie County Department of Health __ f /. Nancy K. Rea, Public Health Administrator Administration Erie County Department of Health I Joseph Trzybinski, Director Administration Erie County Department of Health Signature Date Signature __ /_ Date Public Health is an Organized Community Effort Aimed at Preventing Disease, Prolonging Ute, and Improving Emotional and Physical Efficiency. Appendix B 86 ’ < h< 0 0 1X1 H Q UJ 0 CE H C/> ~ Ul 0 D CE UJ co “■ £ o 0 0 0 UJ Q Q < CZl O H 2 _ z © ,PO J —3 CA ~ - u. — H < < KJ = - oo o o = 5p“^ F H -J <2 "" 00 a UJ “ o -1 d co -2 =h3§S °< O Z) < C2 ~ < cn rs < Q © ■o ■> o Q. >• 2 I fell i shi cn I X o 1 o a a o « D O’ © . m § § ® E J2 >- - 2. ra ?■ g x: o 5 ss h ~ s S.S © Q « - g » § x o >■ o c « 5 H Q_ « © © •C — H o Q 87 e £.§ 1 | 1 iOl 2 n^i = o io ill? Jl 8^ f "li a = 5 Is J 3H y-s t 3 5 i 1 - - 1■h 3U = fl dl umi 1 o c 5 re 5 “ 1 s fl E ©. I f E a t •§■•a s I §e “ 5 I g 3 2- tn 0) Z o .2 1“^ E £•==§=.!< S mu sssnn 1 «s in i? §k z E LU o ■g o o u GC t: X I = J re Si ig < > 5 Cg-= = ~ 211 = § .2 ’“ re .2 s £■•= § < ."i Q tn re re re Z o Q Z> 0 O CC H Z u o o c. o 8 s •§ o 5 § u o cn i 2 55 •» x: 1 5 £ •3 Z u 2 1 ItiiU 2z £ -tc 01 C 8=2? = 2 — 2 = iJ-s ■K HIM i 2 2 3 S £E < e £• •2 i i 2 8 = •I h I ’! i I Ko.:;! .2 - < g. E •f £ _g £ » Hu he r 3ul* O O f- X " 3 £ *3 3 Q t_ 3 .2 Ss8. - 1 3. P1 h O 2 3= 2 o =s s w t> ^2 re .2 < X a > UH31 8 - s g >* V «* u « •* H 7= * U 8 5 = ‘B S g. ,1I ie li n § p >>■= re Z - ».g ° •;2 s -zj E 8 ! 5 o 2 -E. e. s 8 5-^ w o * E H £ 5 .2 •h 'i= c ° E 3 “.2 = .± — S— 2 u tn h- C o o — Z = Z 11 li i i ^11 i ii u I ii V 2 I II i o z U u •■Hre z I. _ o 11 M = h eV eQeo oc~ r-s 1= »1 i8 iS *o §“ iis ^-2 re js li ■g I5 < .2 .2 - 2 | I •5 o tz: ■8 3 “ g.l£ 3 — » p a « .E 3 3 5 H = 5 ““ '-» £ 11 *> tc tn = e 2 y o ! 2 2 •= se £| 5 2 | c -1 i.1 Li •■n 1 I !i 5iIiH in U= =1^ E = •o H iSiil s ll 3 = 5 C 5 H 2g= 1= 3 2 =■ 54 5 2 E 11§ ! B IS 1lz=o re I* il z i g 8 § -J Z 2 E E 1 § 5 *o re — I re ll-■n s > 2? 3 = 8 8|< fa I I « I •111 illiiif f g s 2 s §d u £ .^2 ii I A tn 5 .2 2 2“ i - E - E •8 = u E u g. V .2 3 Z 5 3 & o? til Hire 3 8. fl lh - re " * 8 g. 3o .11 = ^e g V) — k_ 8 =£ £ I § I" < 111 -a = — O- - I Si HI re a §3 ^1-i Si 5i _o |z ,° S M H o = H 2 Q oi rn Zs c ri ° 3 I JE X <2 f =a Si! I -S i J I § 2 ® ~ "c re I F lii "u s cc •E o E LL £ E iH r 3 G- F < O JP 2 re -d LU z F LL O z o LU -I Q. 5 o o = g ® =1 if j u P ii ill . g e-I 1 3 = >2 E £-8 = re 4 s ii i? 1 I O ■5 g 21 3. fl I -11 i CO Q UJ LU Q. o 0 0 F LU CC Q. o E 5 12 s "3 !•= § 1 i. -J J. SEE — o 3 Q & O .S < H ® >» -2 U E G. c S: g c E S Q o g CU w o U S> ff E •c 5 = v> 2 « ~ 3 - ^11 E 3 8 5 al E E O P *o , < fZ— P• L2 z: lj gq u. S H o &2 w > O .£ til ° 5- o Ftls 0 O i< - 2 S Z .= I II I Uli lil 1 — -o — ■i re > 2 re .E Ir I G 3 = 2 e 3 S 5* re 5 * c o S s Q O' - 5 LI _CJ o cc LU LU Ct F } fI 1 il I I h I if I I 'i-3 " “i= -3 & 8 = !:P L la is f dl •Sol « 5£ o E re 1I I s‘j 0 F 0 O > *” - o 1 I o Q *Zk Q G “ —5 o < > < u 51 -2 CZ 3 << 0 H Z < F Q o LL — re re “i 5 3 *£. i 5° cZ-j ■58“ = 2 .2 > = H 2 o o c c £ = -- re g if •= u s LU o ® Q co W -o m < < F < 0 II F 8 3 S tn co § l I e o —* •O lE •- y 2 re <« CC > F CJ ? G « CL CL _ § -£ ,1g Z2 ’o IS 3 Eo T3 sE 1£^9 5 S z o £-2 E 2 8 d= v t CO “ 88 I 1 o S2 < C. c d Z e >5 5 - « re « -S c c 5 § o .2 J2 » Z. c. o § •= 8 -E Q ip a5 >X— O = S .£ “o tj- -±£ 3 *5 8 .2 3 CO gi? ~oC 2 ~ r» 5-P ■= 0 LU F 0 LU F O 2 * ap _6 cc CL 0 z z < co o cc •3 2 o Q 51 I fs ^8 i o LL a 11 < F < Q o CJ -g 2 3S c~ 5 a." 5 § § _ ■I < < 5 z- F» R1 h: £ -2 S 0 0 UJ 0 O a: o. sg ge H re i! 1 I 1 ?I £ I y ii "i z o co _ y O $2 g H g O co h u O' co < < a H cu .-■ -J ‘ = co t= u. = “ c Qi o Eo £ •E ej £ E & 00 Q .S 2 \O < =5 1^ J 1 *s- s > § —> qs Zao > 8 o *S ;2 .E o 2 8 « 3 « S--g u. E .E £ g re •2 <2 = Q ® L- Hi I 2 § * S § •S-5’5 >g 2 If o 3 .2 « ! o III g. « 53 I w > I-1 35 e 5gI 2 u> O 5 5= III Li O 5- < H C2J Z H “ ~ CU co ■15 -J u. S H < o O H Z) o al r- Z < J = H sgS<2 5 Q > c£ co Q c- v-> Z H g< 2 < s = t °51 •g in "ut II = “ II E u w “22 s>» 89 ’ - I 03 Hl 1'22 £J2 i> I Ii 2.1 a tn H I1 Ii 1 1 “I g = 1 >■ ° 2 £ .2 2 i c life f 1«§ s I = I II= 11 %a_ e u < o E u = •= P r 11 i o -g I ■o _> o .E — 5 E o >» I o co c >» •h’ S o J rr •* < < •d d !•= 1 5.1 " -a 2 C H i f i i ! e i o o fi 2 * •I== J= It g r7 < £ 2 1 11 i I 75 «1.1 I ll •1 I r L I d f 11 I o i a .E 1 ■S C 822“ I o 1 if •le o 3 If < < * C3 .. _ E = J” 2 co LLJ H > cn H Q O £ < 0 o LU o cc £< ll o > LL cn rr Z O U. Q_ C/) 0 Z? 3S Q D 0 •H= i-i ih '2-2 | .2 = U .1 2f s s “£ £ §? li “ =1 i il c -J c= a 5 J .“ .2 omH! f:f n=^>5 = Jc.» = =5§ 1? __ __ 11 =1 CJ cn "E o U “I e s^_S =y it £ o >> J tillI iHoH Ji > 1U = 0 i ss £ > -27- -En-f I o > illE I 8 Z-- z £ 8 £“ S O ■g .2 c 0 if 2 2 - c -o S I"iffiy J -E - e s 2 - -2.73 -^ Ti ■S 1= « >9 2 o c f S £O Q £ w o <— ” "e 5 a 0 0 § £ x .5 = E 00 = S» c-HSoo .2- g ?S<2 frf |» ‘ g E c ~ 1 ■• _ _ .gc 1.2 &c & = 5£ § 2 ca — o oo Q r* §• ■3 u -O M I O Hill I ~ E _ _ a Sfi U HP =-a *1 § 13 = 2 ia 5: a 0 i q c a g 2 u —. S u 2 2 « O §£ | ■g 2 11~u 2 3 § ■5 IslH•s i-s 2h | gg rpHii £ § £ ■Stalls e cI c=12 u. E e .2 ■| 3 2 8 u , U Q «O Q ± C. X — • -= oHl 04 q 5 M U to §- "3 5 2 £.§ c <-> o U — -C Ji ■S 2 | T Ji ° O 2 jii till i§±-i hi 1 -TH H-i-f I nil cn 1 2 E J- *« 11* 5 c 3 t ii g £ Z £ co 2.= iKiii o .s S c .± tHfl Ii lillH-r nil I = I ’ 1 ° i 5 .1 riI f 11 ■h = I sW i! I is 0= 1 .± Cu ll H ii ■3 r 1 s ’ ^8- sb I jl i II “ i iI g 2 - :g ^.S = e u O ’•= Q E Eiiliii I | 8 =■ I8 i3 §■:= » “> 2= 1 5 2 1 8-S § E 12 <° 2 H 2 g a .2 2 o *0 I f-E sfPn x > " o 3 g = «#£» <± S s ! i H 3 o = S 2." = f.s§-g«S2 5 a = £ -i = e 1 S -g &-2 £ s-s £ §• £ S. a-E.«■§ 5 2 2. 90 S,FL> 2 = o dt Hi «h ih I i § p H 2-5 *,> 8 = J 2 ? Q s-= "H =1•5 £ ^■1 2 8 2 :s -= s’i £ u a *o o T O o « a is= £ 58 tu •a Wh 11 |t _ 5 .3 " g •2 | *3 » a Q mu islil I o 5u 01 o o 3 = i & 2 H “ 3 O iI •I = P 2 5 S r2 gE 21 U cn LU cc cn o ” u t-a « as u — — V> 40 « n u ih dn 11 1-=1 I *5 « 5*.E £ -o o -a o —1 LU U < £ c .2 g III< ■E-S —- <0 J* -f I!i-i 1 S'? 8 ■ 8 8 8 „ & E =„ E.& 3 -2 i i 5 Bil ir U 0A « oo 2e j j O .£ Hti lilt : s>2£ 51 g-5 I I8 y i It •5 - g 8-.E 2 2 .2 = I •= I >1 E- !=I Ft .2 E 8 — r- se 1 i o E 2 O 3 •E « 1 3 ES e o 2-3 2 « ^2 ! 3 w Hl ® ■O •Hi •L Hi f g ■“ 0 iqj< 8 « <§1 in O =6 1s -S E Q I s ‘S 5 S > LU LU JF 1’1 in He £-U-l & 5 2 2 S' LU CC n=* s Isl i1aE zr~ e •= « O si 5 3 5 .52 DO g. 2 “■ 8 = c 22Z 1 O o X> -a U "Z 3 — g -□ o <“5 8 a fin UH i 1 i :l Hit .=E 8w xH5 c S £ > I S “S ■“ H - :I11^ J |Ui L - -5 o s ti’U nh »Z<£ it-s !• IF M g 8 2 E § 2 g s 81 2’-3 •t 1 o .E 1st = Q O -O 8> z « ° E 4 »«n s t-M 3 -= JT Z5 1 M.n 3 o it n £ -8 M H li 2 « “ 1 il = i I s J ■= .8 co ii, I 3 H £.5 3 = ■s-Mi-s § I is ■H X I = = ■= e: C. o 2 I Mitill 3 f ” co j p.E •5 ?T-= ! = — 2 31 S 1 = t'i § w <:! 1 & h CM IE= HI |,8 a HI I8 1 O “ I't! Hi! iin v= iE s '"I II jj §I “I 3 t -hilLH ■= 8 g ■= E15 s. cn LU 0 cc < - =S fisc-'is^ = on 11! I 1 -E* o a E 12 o i E ±f 11 I5 U E ■n H H = o c Q Hou 91 CO LU O z e s d < H < O 0 ‘is 5",• » > < CL LU u. -J > z z LU Q. N 1 00 O B 8 I'M i 8 “ §I£ cc “’■ -3't; s K-ipl LU w ° < —I o co 2 ilW° Q. a Q 0 > 5 i £°-8 “ l§3 s 8I ° 8S E| z = MF o. >»■ o IM •o _! 'i 5 -I = = i sg E £ " 2 CO < DO ra C- z g mils «"=2£« 8 -z 8 | -2 § ilH H < O "q tn (S — B -• i-§j5 « o H 2£-3 « <- = 2= 5=k-=21Sox - c o c c w -E « 5 »P. 8= <^o « « - = i B's! 88-S“ "E ; " tr CB < CD D a. e 2 I liH I= f1 I 1 Z-e 1L.1 Q = 1=8 I 11 i OH li 5 § ■eI H ilii llll 1 s =5° I 8^1 I? 1CO 5G_ se II mi i-t II 1 n n t li II H 15 5 5 C-Q Appendix C 92 ERIE COUNTY DEPARTMENT OF HEALTH STD CLINIC PATIENT CONSENT FORM I ___________________ grant permission to the ERIE COUNTY DEPARTMENT OF HEALTH to obtain specimens, perform treatments and share information about myself, or my child ______ as may be necessary for proper medical care, so long as I understand the procedures. Date Patient Signature Witness Date Patient Signature Witness Date Patient Signature Witness Date Patient Signature Witness Date Patient Signature Witness Date Patient Signature Witness Date Patient Signature Witness Date Patient Signature Witness Date Patient Signature Witness Date Patient Signature Witness Date Patient Signature Witness c:klsidcon.96 Z X ct u; Appendix D 93 I M U ■ O *- tt X M < X O X X i JE s z o p -J -J - X k k> X _ g X x >- X O w I z 3a» X >• H X K O UJOXXU-X O m O |h a w< 2 f S wz h. I W w OIj<2>Q-< ii UOZOatCEW< wIEOO- § 3 ! •o C3 CL CO s .© i ll