By Nancy K. Lowe, PhD, CNM, FACNM, FAAN, and Nancy A. Ryan-Wenger, PhD, RN, CPNP, FAAN

Transcription

1 Uncomplicated UTIs in women Abstract: Empirical diagnosis and treatment of lower urinary tract infection (UTI) in women is the most common clinical approach due to the urgency of symptoms and cost. This study examines the importance of recognizing common symptoms and accurately diagnosing UTIs in the primary care setting. By Nancy K. Lowe, PhD, CNM, FACNM, FAAN, and Nancy A. Ryan-Wenger, PhD, RN, CPNP, FAAN Photo zilli /istockphoto.com S ymptoms of urinary tract infection (UTI) remain a common presenting problem among women in primary care. Approximately 9 million women per year are seen in offices, clinics, or EDs for UTIs, at a cost of over $2.47 billion. 1 The lifetime prevalence of at least one occurrence of UTI is estimated at over 50% for women. 1 Diagnosis and treatment based on a woman s demographic characteristics and symptoms, sometimes combined with urine dipstick tests for nitrites and leukocyte esterase (LE), are the mainstay of clinical management and consistent with contemporary guidelines by the American College of Obstetricians and Gynecologists. 2 However, the relative inaccuracy of clinical diagnosis of UTIs continues to be raised in the literature, especially due to heightened concerns about unnecessary treatment with antibiotics and antibiotic-resistant bacteria. 1,3-5 The authors conducted a study of 263 military women with either urinary symptoms or both urinary and vaginal symptoms, and systematically evaluated the accuracy of urinary symptoms, urine dipstick tests, and combinations of the two tests in comparison to the standard diagnosis of UTI via urine culture. The study also evaluated advanced practice registered nurses (APRN) clinical diagnoses of UTI compared to urine culture results. Despite current practice recommendations that the diagnosis of lower UTI is based primarily on signs, symptoms, and patient history, the gold standard for diagnosis of UTI is a clean-catch urine culture positive for uropathogens. 6 Given the cost and time delay for results of urine cultures, a range of empirical diagnostic methods is employed including dipstick urinalysis. 6 Research shows that the amount and type of information used to diagnose women with urinary symptoms has no significant impact on diagnostic accuracy. Key words: diagnosis of urinary tract infection, urinary tract infection, urine dipstick tests, urine culture. The Nurse Practitioner May

2 Empirical diagnosis and treatment of urinary symptoms The effectiveness of telephone management of urinary symptoms is rarely evaluated by urine culture because of the difficult logistics of obtaining urine specimens. Safety and effectiveness are typically evaluated by the percentage of women who experience continued or recurrent symptoms after empirical treatment. For example, within 8 weeks (N = 273) and 6 weeks (N = 4,177) after empirical treatment by telephone triage, the percentage of women who made subsequent office visits for recurrent or persistent symptoms was 16.8% (n = 46) and 17.9% (n = 748), respectively. 7,8 Pyelonephritis was diagnosed in 2.2% (n = 6), and 0.5% (n = 21), respectively. In a third study, 72 women with urinary symptoms who called for a primary care provider appointment were randomized to telephone management (n = 36) or office management (n = 36). 9 All of the women were diagnosed and treated for UTI, and all but five provided a urine specimen for analysis and culture prior to taking antibiotics. Positive urine cultures were found in 64.2% (n = 43) of the women. The two groups were not significantly different on symptom scores, satisfaction with care, or urine culture results. The authors noted that the percentage of positive cultures in women diagnosed with UTI was similar to that of a study published in 1980, but did not express concern that nearly one-third of the women had negative cultures, indicating that they were misdiagnosed and treated with antibiotics unnecessarily. Even when women are diagnosed and treated in office or clinic settings, the accuracy of providers diagnoses is not unfailing. For example, in a sample of 111 women with urinary symptoms, 68 (61.3%) received antibiotics, but only 27 (39.7%) had positive urine cultures, and of the 43 (38.7%) women who were not treated, 9 (20.9%) had positive urine cultures. 10 The scope of information used by these providers to make their diagnoses was not described. Diagnostic value of urinary symptoms and point-of-care tests The search for better diagnostic tools for UTI prompted research on the accuracy of urinary symptoms and pointof-care tests in the diagnosis of UTI compared to the gold standard of urine culture. Results from nine research articles were summarized in a systematic review. 11 The highest positive likelihood ratios (LR + ) of single observations were achieved from dipstick urinalysis (LR + = 4.2) and selfdiagnosis based on previous symptoms of UTI (LR + = 4.0), compared to symptoms of hematuria, urinary frequency, costovertebral angle pain, back pain, fever, or dysuria (LR + = 2.0, 1.8, 1.7, 1.6, and 1.6, respectively). Many studies show similar diagnostic accuracy levels for urine nitrites (N) and leukocyte esterase (LE) dipstick tests compared to urine culture. The results of two studies showed that in a sample of 1,583 women with urinary symptoms, compared to urine culture of 100 colony-forming units (CFUs)/mL or greater, the presence of N had a positive predictive value (PPV) of 90%, and a negative predictive power (NPV) of 30%. When N was negative, the PPV of LE + was 79%. 4 This indicates that theoretically, a positive LE test will catch 79% of UTI cases when nitrites are negative. In another study of 408 women with symptoms of UTI, the odds ratios for signs and symptoms were highest for N + at 6.36, and leukocytes (4.52), followed by dysuria (2.76), blood (2.23), protein (1.12), and urgency (1.1). Combinations of signs and symptoms did not improve the odds ratio for N +, although no data were provided to support this statement. 12 Comparison of accuracy rates across studies is complicated by the use of different statistics (LR +, odds ratio, PPV, NPV, sensitivity, specificity) and lack of a standard definition for a positive urine culture. For example, the above studies define UTI as greater than 10 2 CFU/mL greater than 10 3 CFU/mL, or greater than 10 5 CFU/mL of a single pathogenic organism. As the CFU standard increases, the number of UTI diagnoses decrease, the number of non-uti diagnoses increase, and the risk for false negative diagnoses increase. In addition, sample inclusion and exclusion criteria varied among studies. Women with vaginal symptoms accompanying urinary symptoms were often excluded. Despite the fact that in clinical practice women often present with both urinary and vaginal symptoms, the authors found no studies within the last 20 years that reported the accuracy of UTI diagnoses for women with and without vaginal symptoms. The authors current study extends knowledge about the diagnostic value of urinary symptoms and urine dipstick tests among women who seek care for urinary symptoms alone or in combination with vaginal symptoms. Previous research has evaluated providers accuracy in the diagnosis of UTI under various circumstances such as telephone management and in office settings where the knowledge of patient history, physical exam, and point-of-care testing used to make clinical diagnoses is varied. This study was unique in that experienced APRNs followed a systematic protocol that included all of these recommended sources of data and that the authors compared the accuracy of their clinical diagnoses to urine culture in women with and without vaginal symptoms. The research questions were: 1. What is the accuracy (PPV and NPV) of urinary symptoms, dipstick urinalysis (N and LE), and their combinations, compared to urine culture in the diagnosis of UTI in symptomatic women with or without vaginal symptoms? 42 The Nurse Practitioner Vol. 37,. 5

3 2. What is the accuracy of APRNs clinical diagnoses of UTI compared to urine culture in symptomatic women with or without vaginal symptoms? Methods Setting and sample This report is a secondary analysis of data from the authors study on the accuracy of self-diagnosis of genitourinary infection in 715 military women. 13 The participants included in this analysis are the subset of military women (N = 263) who presented at a United States Army or Navy troop medical clinic with one or more of the classic symptoms of UTI (burning, urgency, or frequency). The participants ranged from 18 to 54 years of age (mean = 26.4, median = 24, mode = 21), and nearly half were married/living with a significant other (24, 47.4%) and one-third were single (n = 87, 33.3%) (see Demographic characteristics). Consistent with the demographics of military women, the racial and ethnic distribution was 41% White, 30% Black, and 20.1% Hispanic, and rank distribution was 1/4 enlisted, 1/3 noncommissioned officer, and less than 10% commissioned officers. Procedure The procedure for the parent study has been previously described in detail. 13 A relevant aspect of this report is that women presenting with at least one symptom of UTI who consented to participate were seen by one of four mastersprepared APRNs who were nationally certified in women s health, and had 6 to 11 years of experience in that role. The APRNs used a standardized clinical research protocol to conduct a clinical interview and evaluate clinical signs through a physical exam and assessment of a clean-catch urine specimen for N and LE. The APRNs made their own clinical diagnoses at the time of exam and treated the women as appropriate. Clean-catch urine specimens from all the women were sent to the hospital lab for culture. A positive urine culture was defined as 10 5 CFU/mL or greater of uropathic organisms, consistent with traditional criteria and past research. 2,10,11 Follow-up for untreated positive urine culture results occurred as needed. Analysis The accuracy of urinary symptoms, urine N and LE, and their combinations in the diagnosis of culture-confirmed UTI was measured in terms of PPV and NPV, and their 95% confidence intervals. Ideally, both PPV and NPV should approach 100%. These statistics reflect the realities of clinical practice, such as the probability that symptoms and signs will accurately differentiate UTIs and non-utis confirmed by urine culture. The accuracy of APRN s clinical diagnoses was evaluated further for error in treatment decisions. Demographic characteristics (N = 263) Demographic Characteristic n % Race/Ethnicity American Indian/Alaska Native or Native Hawaiian/Pacific Islander Asian Black White Hispanic More than one race Education High School Graduate or GED Some College Associate Degree College Graduate Post-Graduate Marital Status Single Married/Living with significant other Divorced/Separated Military Branch Army Navy Air Force/Marine/Coast Guard Military Rank Enlisted ncommissioned Officer Warrant Officer/Junior Officer Senior Officer Results Of the 263 participants, 153 (58.2%) presented with urinary symptoms alone and 110 (41.8%) presented with a combination of urinary and vaginal symptoms. Overall, there were 137 positive urine cultures representing 10 different uropathic microorganisms, of which Escherichia coli (E. coli) was the most common (03, 75.2%) (see Frequency and percentage of uropathic microorganisms cultured at 10 5 CFU/mL). Predictive value of urinary symptoms and dipstick urinalysis One hundred forty-three women presented with only urinary symptoms. Among 50 women with negative N and LE, there were 14 positive urine cultures (28%), and for the 7 women who had positive N only, all 7 had a positive urine culture. Sixty-four women had a positive LE only, of whom The Nurse Practitioner May

4 49 (76.6%) had positive urine cultures, while 32 women had positive N and LE, of whom 27 (84.4%) had positive cultures (see Women presenting with urinary symptoms only). One hundred ten women presented with both urinary and vaginal symptoms. Among the 49 women with a negative urine dipstick for both N and LE, there were 8 (16.3%) positive urine cultures. Only 3 women had positive N only, and 2 of the urine cultures were positive. Among the 41 women with LE positive only, there were 15 (36.6%) positive urine cultures, and for the 17 women with both N and LE positive on dipstick, there were 14 (82.4%) positive urine cultures (see Women presenting with urinary and vaginal symptoms). The data were further analyzed to determine the PV and NPV of urine culture for symptoms alone, urine dipstick results alone, and urine dipstick in combination with symptoms (see Accuracy of symptoms, urine dipstick, and combinations to predict urine culture). Only combinations with a frequency of 10 or more cases were analyzed. In the entire sample of 263 participants, one-fourth (n = 66, 25.1%) of the women experienced only one of the three classic urinary symptoms, 29.7% (n = 78) had two symptoms, and 44.9% (n=118) had the symptom triad of burning, urgency, and frequency. The PPV of a single symptom or combination of other symptoms ranged from 28% for only frequency symptoms to a high of 66.1% for the symptom triad. NPVs are important because they indicate the probability that the absence of selected symptoms and/or negative dipstick results would be consistent with a negative culture result. NPV was fairly stable at 45.4% to 48.7%, with the exception of the symptom triad (59.4%). The 95% confidence intervals Frequency and percentage of uropathic microorganisms cultured at 10 5 CFU/mL. Microorganism Frequency Percent growth E. coli Group B streptococcus Staphylococcus saprophyticus Proteus mirabilis Citrobacter koseri Klebsiella pneumoniae Enterobacter aerogenes Citrobacter freundii Gamma Streptococcus group D enterococcus Serratia species Total were wide for all of the symptoms, ranging from 17.7% to 58.9% for PPVs and 12.4% to 15.9% for NPVs. A narrow confidence interval minimizes the potential margin of diagnostic error (see Positive and negative predictive values). 14 While it is unlikely that urine dipstick would be the only information used to diagnose UTIs, it is instructive to note that with positive LE alone and in combination with positive N, the PPV increases to 84% and 100%, respectively, but these findings occurred in only about one-fourth of the women in the study. NPVs were similar to those found with symptoms alone, and again, 95% confidence intervals were wide for both PPVs and NPVs. When symptoms and urine dipstick results were combined, only an estimated 44% of the sample had one of the four combinations. The most accurate prediction of positive culture occurred when all three classic symptoms were present, and the urine was positive for both N and LE (PPV = 89.1%). However, only 29 (11.5%) of the entire sample had this combination. NPVs were similar to those for symptoms and urine dipstick results alone, and 95% confidence intervals were wide. Accuracy of APRNs clinical diagnosis of UTI Of the 263 diagnoses made by APRNs, 65.7% (73) were confirmed by urine culture. APRNs accurately diagnosed 124 (47.1%) women with UTI and 49 (18.6%) women with non-uti. The false positive rate was 29.3%, indicating that 77 women were unnecessarily treated with antibiotics (commission errors of treatment), and the false negative rate was 4.9%, indicating that 13 women did not receive appropriate antibiotics for their UTI infection (omission errors of treatment) at the time of their clinical evaluation. Diagnostic accuracy rates were similar between the two groups of women without vaginal symptoms (64.7%, n = 90) and with vaginal symptoms (67.3%, n = 74). False positive and false negative rates for the two groups were also similar to those of the entire group. It is important to note that the women with both urinary and vaginal symptoms were less likely to have a culture-confirmed UTI (30.9%) as opposed to women with urinary symptoms only (58.8%). Discussion The findings support current knowledge about the relatively poor diagnostic value of urinary symptoms alone, urine N and LE alone, or in combination. The study protocol required APRNs to conduct a standardized clinical history, physical exam, and clean-catch dipstick urinalysis before making a diagnosis using their own clinical judgment. The research setting also guaranteed that the APRNs had sufficient time to conduct the clinical protocol in an uninterrupted manner without time constraints. Despite the additional time and clinical information, only approximately two-thirds of their 44 The Nurse Practitioner Vol. 37,. 5

5 Women presenting with urinary symptoms only The flow chart represents the urine dipstick results, urine culture results, and clinical diagnoses of UTI for women with urinary symptoms only. Women presenting with urinary symptoms only N = 153 Clean-catch urine dipstick results N LE n = 50 (32.7%) n = 7 (4.6%) LE + n = 64 (41.8%) N + LE+ n = 32 (20.9%) Uropathic culture results CFU 10 5 CFU 10 5 CFU 10 5 CFU 10 5 n = 36 (23.5%) 4 (9.2%) n = 0 n = 7 (4.6%) 5 (9.8%) n = 49 (32%) n = 5 (3.3%) n = 27 (17.6%) APRN clinical diagnosis of UTI prior to urine culture results n = 6 (3.9%) n = 30 (19.6%) n = 4 (2.6%) 0 (6.5%) n = 0 n = 7 (4.6%) n = 2 (1.3%) 3 (8.5%) n = 2 (1.3%) n = 47 (30.7%) (0.6%) n = 4 (2.6%) (0.6%) n = 26 (17%) N = nitrites, LE = leukocyte esterase, CFU = colony-forming units/ml, APRN = Advanced Practice RN, UTI = urinary tract infection. Accurate diagnosis False positive diagnosis False negative diagnosis of UTI The Nurse Practitioner May

6 Women presenting with urinary and vaginal symptoms The flowchart represents the urine dipstick results, urine culture results, and clinical diagnoses of UTI for women with both urinary and vaginal symptoms. Women presenting with urinary and vaginal symptoms N = 110 Clean-catch urine dipstick results N LE N = 49 (44.5%) N + N = 3 LE + N = 41 (37.3%) N + L+ N = 17 (15.5%) Uropathic culture results CFU 10 5 CFU 10 5 CFU 10 5 CFU 10 5 n = 41 (37.2%) n = 8 (7.3%) n = 0 n = 3 n = 26 (26.3%) 5 (1.5%) N + n = 3 4 (12.7%) APRN clinical diagnosis of UTI prior to urine culture results n = 31 (28.2%) 0 (9%) n = 3 n = 5 (4.5%) (0.9%) n = 2 (1.8%) n = 9 (8.2%) 7 (15.5%) (0.9%) 4 (12.7%) n = 0 n = 3 (0.9%) 3 (11.8%) N = nitrites, LE = leukocyte esterase, CFU = colony-forming units/ml, APRN = Advanced Practice RN, UTI = urinary tract infection. Accurate diagnosis False positive diagnosis False negative diagnosis 46 The Nurse Practitioner Vol. 37,. 5

7 Accuracy of symptoms, urine dipstick, and combinations to predict urine culture Symptoms N (%) PPV (CI) NPV (CI) Burning only 31 (11.4%) 29.0% ( ) 45.5% ( ) Urgency only 10 (3.7%) 60.0% ( ) 48.7% ( ) Frequency only 25 (9.2%) 28.0% ( ) 46.0% ( ) Burning and urgency 17 (6.2%) 52.9% ( ) 48.4% ( ) Burning and frequency 12 (4.4%) 58.3% ( ) 48.7% ( ) Urgency and frequency 49 (17.9%) 42.9% ( ) 46.4% ( ) Burning, urgency, and frequency 118 (43.2%) 66.1% ( ) 59.4% ( ) Urine dipstick LE only 107 (39.2%) 60.7% ( ) 54.2% ( ) N only 10 (3.7%) 100% ( ) 50.2% ( ) LE and N 50 (18.3%) 84.0% ( ) 55.6% ( ) Negative LE and negative N 106 (38.8%) 22.6% ( ) 29.9% ( ) Combination of symptoms with positive N and/or LE Burning, urgency, and LE 10 (3.7%) 70.0% ( ) 49.0% ( ) Urgency, frequency, and LE 21 (7.7%) 52.4% ( ) 48.4% ( ) Burning, urgency, frequency, and LE 53 (19.4%) 69.8% ( ) 52.7% ( ) Burning, urgency, frequency, N and LE 29 (10.6%) 89.7% ( ) 52.9% ( ) diagnoses were accurate when evaluated against the gold standard of urine culture. An estimated 30% of the women were erroneously diagnosed and treated for UTI with antibiotics, a finding similar to the results of other studies. Regardless of the amount and type of information used to diagnose UTI, error rates range from 25.8% to 39.7%. 9,10 This is a concern because the unnecessary use of antibiotics contributes to the development of antibiotic-resistant organisms. Only about 5% of the APRN s diagnoses of non- UTI were in error, meaning that 5% of the women actually had a UTI but were not treated for it. The authors have extended the science of UTI diagnosis by demonstrating that a comprehensive clinical history and physical exam does not appreciably improve diagnostic accuracy of UTI in women with urinary symptoms with and without vaginal symptoms. The presence of vaginal symptoms does not interfere with the accuracy of UTI or non-uti diagnoses, but it is important to note that the accurate diagnosis of non-uti was six times greater in women with vaginal symptoms (36.4%) than women with only urinary symptoms only (5.9%). This study confirms that despite the actions of welltrained and experienced clinicians with adequate time for a full clinical evaluation, the accurate diagnosis of UTI from clinical symptoms and signs remains difficult. APRNs were more likely to over treat for UTI (29.3% commission errors of treatment) than under treat (4.9% omission errors of treatment) when using a diagnostic urine culture criterion of 10 5 CFU/mL. Therefore, with a goal to reduce unnecessary treatment with antibiotics, data suggest that in both women presenting with symptoms of UTI alone or in combination with vaginal symptoms and negative urine dipsticks for both N and LE, an appropriate clinical consideration is to postpone antibiotic treatment until culture results are known since only 28% and 16.3% of these women had positive cultures. Depending on the population and the individual woman s sexual history, screening for sexually transmitted infections (STIs) may also be appropriate. However in this sample, in which STI screening was done on all participants per protocol, only 7 women (2.8%) had chlamydia and 2 had gonorrhea (less than 1%). Urethritis rather than cystitis (UTI) may be the explanation for the presence of clinical symptoms and may be amenable to symptomatic treatment unless it is related to chlamydia. Until culture results are known, symptomatic treatment with pyridium, cranberry extracts, and increased fluids can be initiated. The study data did not include the investigation of more subtle aspects of clinical assessment and diagnostic reasoning. Data were not collected to allow the evaluation of severity of symptoms, other related signs and symptoms, or rapid onset that the APRNs may have used in their clinical decision making. The APRNs undoubtedly incorporated additional clinical data such as internal versus external dysuria, onset of dysuria, small voids, gross hematuria, and suprapubic pain or tenderness into their clinical decisions. However, treatment errors as determined by urine culture still occurred. The Nurse Practitioner May

8 Positive and negative predictive values Positive Predictive Value Negative Predictive Value Percentage Frequency only Sx = Symptom n=25 n=31 n=49 n=17 n=12 n=10 n=118 n=21 n=53 n=10 n=29 Burning only Urgency & frequency Burning & urgency Burning & frequency Urgency only Burning urgency & frequenct (Sx Triad) Urgency, frequenct & leukocyte esterase + Sx Triad & leukocyte esterase + Burning, urgency & leukocyte esterase + Sx Triad, leukocyte esterase + & Nitrites + Consistent with the body of the clinical literature, E. coli was the most predominant organism associated with UTI. Therefore, APRNs must continue to teach women and young girls the essentials of protective perineal hygiene and other health behaviors known to reduce the incidence and/or reoccurrence of UTIs. The findings also support the need for a systematic detailed history when evaluating women either over the phone or in person with symptoms of UTI. While empiric treatment is common and considered a cost-effective standard of care with or without dipstick urinalysis, further research is indicated to identify whether a systematic analysis of severity of symptoms can improve diagnostic accuracy particularly with a goal to reduce unnecessary antibiotic treatment. REFERENCES 1. Griebling TL. Urologic diseases in America project: trends in resource use for urinary tract infections in women. J Urol. 2005;173(4): American College of Obstetricians and Gynecologists (ACOG). Treatment of urinary tract infections in nonpregnant women. Obstet Gynecol. 2008; 111(3): Little P, Turner S, Rumsby K, et al. Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study. Health Technol Assess. 2009;13(19):iii-iv, ix-xi, Nys S, van Merode T, Bartelds AI, Stobberingh EE. Urinary tract infections in general practice patients: diagnostic tests versus bacteriological culture. J Antimicrob Chemother. 2006;57(5): Epub 2006 Mar Ellington MJ, Livermore DM, Pitt TL, Hall LM, Woodford N. Mutators among CTX-M beta-lactamase-producing Escherichia coli and risk for the emergence of fosfomycin resistance. J Antimicrob Chemother. 2006;58(4): Epub 2006 Aug National Guideline Clearinghouse. Guideline Synthesis: Diagnosis and Management of Uncomplicated Lower Urinary Tract Infection. Rockville, MD: National Guideline Clearinghouse; Schauberger CW, Merkitch KW, Prell AM. Acute cystitis in women: experience with a telephone-based algorithm. WMJ. 2007;106(6): Vinson DR, Quesenberry CP. The safety of telephone management of presumed cystitis in women. Arch Intern Med. 2004;164: Barry HC, Hickner J, Ebell MH, Ettinhofer T. A randomized controlled trial of telephone management of suspected urinary tract infections in women. J Fam Pract. 2001;50(7): O Brien K, Hillier S, Simpson S, Hood K, Butler C. An observational study of empirical antibiotics for adult women with uncomplicated UTI in general practice. J Antimicrob Chemother. 2007;59(6): Epub 2007 Apr Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 2002;287(20): Little P, Turner S, Rumsby K, et al. Developing clinical rules to predict urinary tract infection in primary care settings: sensitivity and specificity of near patient tests (dipsticks) and clinical scores. Br J Gen Pract. 2006;56(529): Ryan-Wenger NA, Neal JL, Jones AS, Lowe NK. Accuracy of vaginal symptom self-diagnosis algorithms for deployed military women. Nurs Res. 2010;59(1): Straus SE, Richardson WS, Glasziou P, Haynes RB. Evidence-based Medicine: How to Practice and Teach EBM. 3rd ed. Edinburgh: Elsevier, Churchill, Livingstone, This study was funded by the National Institutes of Health, National Institute of Nursing Research. Nancy K. Lowe is a professor and division chair of Women, Children, and Family Health at the University of Colorado College of Nursing in Aurora, Colo. Nancy A. Ryan-Wenger is the director of nursing research at Nationwide Children s Hospital in Columbus, Ohio. The authors have disclosed that they have no financial relationships related to this article. DOI /01.NPR f8 48 The Nurse Practitioner Vol. 37,. 5