Amiodarone versus a beta-blocker to prevent atrial fibrillation after cardiovascular surgery.

BACKGROUND: Both amiodarone and beta-blockers have been shown to decrease the incidence of atrial fibrillation after cardiovascular surgery. However, the superior agent has not been identified. METHODS: We performed a pilot study on 102 patients (68 men, mean age 65 +/- 10 years, mean left ventricular ejection fraction 0.53 +/- 0.12) undergoing cardiovascular surgery (94 coronary artery bypass grafting [CABG], 5 valvular surgery only, and 3 CABG + valvular surgery). The patients were randomized to receive amiodarone (1 g/d intravenously x 48 hours, then 400 mg/d orally until discharge) or propranolol (1 mg intravenously every 6 hours x 48 hours, then 20 mg orally four times a day until discharge). Atrial fibrillation was defined as lasting longer than 1 hour or resulting in hemodynamic compromise. RESULTS: The incidence of postoperative atrial fibrillation was 16.0% (8/50) in the amiodarone group and 32.7% (17/52) in the propranolol group (P =.05). The mean length of stay was 8.8 +/- 3.5 days for amiodarone-treated patients and 8.4 +/- 2.7 days for propranolol-treated patients (P not significant). Serious adverse events were uncommon and similar in each group. CONCLUSION: Early intravenous amiodarone, followed by oral amiodarone, appears to be superior to propranolol in the prevention of postoperative atrial fibrillation. It is well tolerated and can be started at the time of surgery. However, the use of amiodarone did not result in a reduction in the length of hospital stay.

Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States).

OBJECTIVES: Few studies of smoking and cervical carcinoma have addressed the rare cervical adenocarcinomas or used DNA-based tests to control for human papillomavirus (HPV) infection. METHODS: This multicenter case-control study included 124 adenocarcinoma cases, 307 community controls (matched on age, race, and residence to adenocarcinoma cases), and 139 squamous carcinoma cases (matched on age, diagnosis date, clinic, and disease stage to adenocarcinoma cases). Participants completed risk-factor interviews and volunteered cervical samples for PCR-based HPV testing. Polychotomous logistic regression generated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for both histologic types. RESULTS: Eighteen percent of adenocarcinoma cases, 43% of squamous carcinoma cases, and 22% of controls were current smokers. After control for HPV and other questionnaire data, adenocarcinomas were consistently inversely associated with smoking (e.g. current: OR = 0.6, 95% CI 0.3-1.1; > or = 1 pack per day: OR = 0.7, 95% CI 0.4-1.3), while squamous carcinomas were positively associated with smoking (e.g. current: OR = 1.6, 95% CI 0.9-2.9; > or = 1 pack per day: OR = 1.8, 95% CI 1.0-3.3). Results in analyses restricted to HPV-positive controls were similar. CONCLUSION: Smoking has opposite associations with cervical adenocarcinomas and squamous carcinomas. Although both histologic types are caused by HPV and arise in the cervix, etiologic co-factors for these tumors may differ.

Accelerated dobutamine stress testing: safety and feasibility in patients with known or suspected coronary artery disease.

BACKGROUND: Dobutamine pharmodynamics require approximately 10 min to reach steady state. Despite this, standard dobutamine stress echo typically uses 3-min stages of advancing dobutamine doses because of safety concerns. HYPOTHESIS: In patients with a high pretest probability of coronary artery disease (CAD), a continuous infusion of high-dose dobutamine is a feasible and safe method for performing a dobutamine stress test. METHODS: Forty-seven consecutive patients (mean age 64 +/- 11 years) with 3.0 +/- 1.4 cardiac risk factors underwent dobutamine stress testing utilizing a single, high-dose (40 mcg/kg/min), continuous dobutamine infusion. The 40 mcg/kg/min infusion was continued for up to 10 min or until a test endpoint had been reached. If a test endpoint was not achieved, atropine (up to 1.0 mg) was added. RESULTS: Heart rate rose from 71 +/- 12 to 137 +/- 18 beats/min at peak (p<0.0001) with a concomitant change in systolic blood pressure (143 +/- 35 vs. 167 +/- 38 mmHg; p = 0.001) but no change in diastolic blood pressure (74 +/- 19 vs. 75 +/- 18 mmHg; p = NS). Target heart rate was achieved in 20 of 47 (43%) patients with accelerated dobutamine alone and in 34 of 47 (72%) with the addition of atropine. An average of 11.6 +/- 3.7 min was required to obtain target heart rate. Subjective sensations from the dobutamine occurred in 49% of patients (palpitations 21%, nausea 6%, chest pain 6%, headache 6%, dizziness 13%), mild arrhythmia in 48% of patients (ventricular premature beats 38%, supraventricular tachycardia 10%), and one patient had nonsustained ventricular tachycardia. CONCLUSION: A single, high-dose (40 mcg/kg/min) dobutamine-atropine protocol provides an efficient means of performing dobutamine stress echocardiography with a similar symptom profile as conventional dobutamine infusion protocols in patients with a high pretest probability of CAD. Randomized, controlled studies will be necessary to assess the sensitivity and specificity of this accelerated dobutamine echo protocol.

Evaluation of self-collected cervicovaginal cell samples for human papillomavirus testing by polymerase chain reaction.

As human papillomavirus (HPV) becomes accepted as the central cause of cervical cancer, longitudinal studies are shifting focus away from causality to a more detailed investigation of the natural history of HPV infections. These studies commonly require repeated samples for HPV testing over several years, usually collected during a pelvic exam, which is inconvenient to the participants and costly to the study. To alleviate the inconvenience and cost of repeated clinic visits, it has been proposed that women collect cervicovaginal cells themselves, hopefully increasing participation in the natural history studies. We evaluated the technical feasibility of self-collection of cervicovaginal cells using a Dacron swab for HPV DNA detection. We compared the self-collected swab sample and two clinician-administered swab samples (one from the endocervix and another from the ectocervix) from a total of 268 women participating in a case-control study of adenocarcinoma and squamous cell carcinomas of the uterine cervix (111 cases and 157 controls). HPV DNA was detected and genotyped using an L1 consensus PCR assay. The overall agreement between the clinician- and self-collected swabs was excellent [88.1%; kappa = 0.73 (95% confidence interval (CI), 0.61-0.85)]. The correlation was highest between the two clinician-administered swabs [kappa = 0.81 (95% CI, 0.69-0.93)] but was still excellent when comparing either clinician-administered swab to the self-administered sample [kappa = 0.75 (95% CI, 0.63-0.87) and 0.67 (95% CI, 0.55-0.79) for ectocervix and endocervix, respectively]. The type-specific agreement between samples was higher for high-risk, or cancer-associated, HPV genotypes than for low risk, noncancer-associated HPV genotypes when comparing the self-administered swab sample to the clinician-administered swab sample (kappa = 0.78 for high-risk versus 0.66 for low-risk HPV infections, t = -1.45, P = 0.15). The decrease in agreement for low risk types was largely attributable to an increased detection of these types in the self-administered sample (McNemar's chi2 = 6.25, P = 0.01 for clinician- versus self-administered swab comparisons). The agreement did not vary significantly by age, menopausal status, case status, or clinic center. We have demonstrated that a self-collected Dacron swab sample of cervicovaginal cells is a technically feasible alternative to clinician-administered cervical cell collection in natural history studies of HPV and cervical cancer.

Atrial pacing for the prevention of atrial fibrillation after cardiovascular surgery.

OBJECTIVE: The purpose of this study was to determine the efficacy of atrial pacing in the prevention of atrial fibrillation following cardiovascular surgery. BACKGROUND: Although pharmacologic therapy has been used to help prevent postoperative atrial fibrillation, it suffers from limited efficacy and adverse effects. In the nonoperative setting, novel pacing strategies have been shown to reduce recurrences of atrial fibrillation and prolong arrhythmia-free periods in patients with paroxysmal atrial arrhythmias. METHODS: A total of 154 patients (115 men; mean age, 65 +/- 10 years; ejection fraction, 53 +/- 10%) undergoing cardiac surgery (coronary artery bypass surgery, 88.3%; aortic valve replacement, 4.5%; coronary bypass + aortic valve replacement, 7.1%) had right and left atrial epicardial pacing electrodes placed at the time of surgery. Patients were randomized to either no pacing, right atrial (RAP), left atrial (LAP) or biatrial pacing (BAP) for 72 h after surgery. Beta-adrenergic blocking agents were administered concurrently to all patients following surgery. RESULTS: There was a reduction in the incidence of postoperative atrial fibrillation from 37.5% in patients receiving no postoperative pacing to 17% (p < 0.005) in patients assigned to one of the three pacing strategies. The length of hospital stay was reduced by 22% from 7.8 +/- 3.7 days to 6.1 +/- 2.3 days (p = 0.003) in patients assigned to postoperative atrial pacing. The incidence of atrial fibrillation was lower in each of the paced groups (RAP, 8%; LAP, 20%; BAP, 26%) compared with patients who did not receive postoperative pacing (37.5%). CONCLUSION: Postoperative atrial pacing, in conjunction with beta-blockade, significantly reduced both the incidence of atrial fibrillation and the length of hospital stay following cardiovascular surgery. Additional studies are needed to determine the most effective anatomic pacing site.

Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix.

INTRODUCTION: Exogenous hormones may influence the development of cervical adenocarcinomas. Incidence rates of adenocarcinomas and use of noncontraceptive hormones have increased since the 1970s, but few studies have investigated this potential relationship. METHODS: We conducted a multicenter case-control study of 124 women with adenocarcinomas, 139 women with squamous cell carcinomas matched on age, diagnosis date, clinic, and stage of disease (in situ or invasive) to adenocarcinoma cases, and 307 healthy community controls who were also matched on age, ethnicity, and residence to adenocarcinoma cases. Participants completed in-person interviews regarding exogenous hormone use before diagnosis and other risk factors and volunteered cervical samples for human papillomavirus (HPV) testing via a PCR-based method. Odds ratios (ORs) with 95% confidence intervals (CIs) estimated relative risks. RESULTS: Only 13 adenocarcinoma cases (10.5%), 7 squamous carcinoma cases (5%), and 20 controls (6.5%) had used noncontraceptive hormones for menopausal symptoms, irregular periods, or disease prevention; most use was short-term, former use. Ever-use was associated with adenocarcinomas (OR = 2.1, 95% CI 0.95-4.6) but not squamous carcinomas (OR = 0.85, 95% CI 0.34-2.1). No trends were seen with duration of use or ages at first use, but unopposed estrogens were positively associated with adenocarcinomas (OR = 2.7). Unopposed estrogens remained associated with adenocarcinomas (OR = 2.0) when analyses were restricted to the HPV-positive controls. Menopausal status was not associated with adenocarcinomas or squamous carcinomas and did not modify the other associations. CONCLUSION: Although small numbers warrant tentative conclusions, exogenous estrogens, especially unopposed estrogens, were positively associated with adenocarcinomas. Noncontraceptive hormones were negatively but weakly associated with squamous carcinomas.

Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica.

BACKGROUND: Human papillomavirus (HPV) is the main cause of cervical neoplasia. Because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of HPV infection and the risk associated with various HPV types. METHODS: We screened 9175 women in Guanacaste, Costa Rica, to obtain a referent standard final diagnosis, and tested 3024 women for more than 40 types of HPV with a polymerase chain reaction-based system. RESULTS: Among women with normal cytology, HPV infections peaked first in women younger than 25 years, and they peaked again at age 55 years or older with predominantly non-cancer-associated types of HPV and uncharacterized HPV types. Low-grade squamous intraepithelial lesions (LSILs) (n = 189) decreased consistently with age. The prevalence of high-grade squamous intraepithelial lesions (HSILs) (n = 128) peaked first around age 30 years and again at age 65 years or older. Seventy-three percent of LSILs were HPV positive, with HPV16 being the predominant type (16% of positive subjects). HPV was found in 89% of HSILs and 88% of cancers, with HPV16 being strongly predominant (51% and 53% of positive subjects). Virtually all HSILs and cancers had cancer-associated HPV types, with high odds ratios (ORs) and attributable fractions around 80%. Risk for HPV16 was particularly high (OR for HSILs = 320, 95% confidence interval [CI] = 97-1000; OR for cancer = 710, 95% CI = 110-4500). CONCLUSIONS: We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.

HPV DNA testing in cervical cancer screening: results from women in a high-risk province of Costa Rica.

CONTEXT: Human papillomaviruses (HPVs) are known to cause most cervical cancer worldwide, but the utility of HPV DNA testing in cervical cancer prevention has not been determined. OBJECTIVE: To provide comprehensive data on the screening performance of HPV testing for the most common carcinogenic types, at different levels of analytic sensitivity. DESIGN: Laboratory analysis conducted during 1993-1995, using 3 cytologic techniques and cervicography, followed by colposcopic examination of women with any abnormal cervical finding, to detect all high-grade intraepithelial lesions and cancer (reference standard of clinically significant disease). The HPV testing was performed subsequently with masking regarding clinical findings. SETTING: Guanacaste Province, Costa Rica, a region with a high age-adjusted incidence of cervical cancer. PARTICIPANTS: Of 11742 randomly selected women, 8554 nonpregnant, sexually active women without hysterectomies underwent initial HPV DNA testing using the original Hybrid Capture Tube test; a stratified subsample of 1119 specimens was retested using the more analytically sensitive second generation assay, the Hybrid Capture II test. MAIN OUTCOME MEASURES: Receiver operating characteristic analysis of detection of cervical high-grade intraepithelial lesions and cancer by HPV DNA testing based on different cut points of positivity. RESULTS: An analytic sensitivity of 1.0 pg/mL using the second generation assay would have permitted detection of 88.4% of 138 high-grade lesions and cancers (all 12 cancers were HPV-positive), with colposcopic referral of 12.3% of women. Papanicolaou testing using atypical squamous cells of undetermined significance as a cut point for referral resulted in 77.7% sensitivity and 94.2% specificity, with 6.9% referred. Specificity of the second generation assay for positivity for high-grade lesions and cancer was 89.0%, with 33.8% of remaining HPV DNA-positive subjects having low-grade or equivocal microscopically evident lesions. The higher detection threshold of 10 pg/mL used with the original assay had a sensitivity of 74.8% and a specificity of 93.4%. Lower levels of detection with the second generation assay (<1 pg/mL) proved clinically nonspecific without gains in diagnostic sensitivity. CONCLUSIONS: In this study population, a cut point of 1.0 pg/mL using the second generation assay permitted sensitive detection of cervical high-grade lesions and cancer, yielding an apparently optimal trade-off between high sensitivity and reasonable specificity for this test. The test will perform best in settings in which sensitive detection of high-grade lesions and cancer is paramount. Because HPV prevalence varies by population, HPV testing positive predictive value for detection of high-grade lesions and cancer will vary accordingly, with implications for utility relative to other cervical cancer screening methods.

Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas.

To assess the hypothesis that oral contraceptives (OCs) increase the risk of cervical adenocarcinomas, we conducted a six-center case-control study of 124 patients with adenocarcinomas, 139 with squamous cell carcinomas, and 307 population controls. Women between the ages of 18 and 69 who were newly diagnosed with cervical adenocarcinomas between 1992 and 1996 were eligible. Healthy female controls and a second case group of incident cervical squamous cell carcinomas were matched to the adenocarcinoma cases. All participants were interviewed regarding OCs, other risk factors for cervical carcinoma, and utilization of cytological screening, and a PCR-based test determined HPV genotype of cervical samples for both case groups and controls. Use of OCs was positively and significantly associated with adenocarcinomas and positively but weakly associated with squamous cell carcinomas. Associations between OCs and invasive adenocarcinomas (n = 91), squamous cell carcinoma in situ (n = 48), and invasive squamous cell carcinomas (n = 91) disappeared after accounting for HPV infection, sexual history, and cytological screening, but a positive association remained between current use of OCs and cervical adenocarcinoma in situ (n = 33). This association persisted after stratification by screening and sexual history and after restriction according to HPV status, but small numbers made it difficult to exclude detection bias, selection bias, or residual confounding by HPV as potential explanations Current OC use was associated with cervical adenocarcinomas in situ, but we saw no other evidence that OCs independently increase the risk of cervical carcinomas.

Utility of liquid-based cytology for cervical carcinoma screening: results of a population-based study conducted in a region of Costa Rica with a high incidence of cervical carcinoma.

BACKGROUND: In a study using a split-sample design, liquid-based cytology (ThinPrep Processor, Cytyc Corporation, Boxborough, MA) was compared with the conventional Papanicolaou (Pap) smear in Guanacaste, Costa Rica. The study provides the first population-based comparison of the ThinPrep screening technology and includes "gold standard" measures of diagnostic accuracy. METHODS: The population-based study was performed among over 8000 women residing in a Costa Rican province with a high incidence of cervical carcinoma. Conventional smears were prepared and diagnosed in Costa Rica, while the residual material on the sampling device was collected into a liquid preservative and shipped to the U.S., where ThinPrep cytologic slides were prepared and diagnosed. Cytologic diagnoses based on the two techniques, categorized according to the Bethesda System, were compared with a "gold standard" final case diagnosis for each patient, also based on Bethesda terminology, that reflected an integrated interpretation of all available data, including cytology, histology, and cervicography. Results were also compared with the results of HPV DNA detection (Hybrid Capture, Digene Corporation, Silver Spring, MD). RESULTS: ASCUS was the threshold for colposcopy referral. There were significantly more women referred according to this threshold with the ThinPrep slide (12.7%) than with the conventional smear (6.7%, P<0.001). Compared with the final case diagnosis, referral by ThinPrep slides detected 92.9% of cases with high grade squamous intraepithelial lesions (HSIL) and 100% of carcinoma cases. Smears detected 77.8% of HSIL and 90.9% of carcinomas. Thus, ThinPrep cytology was significantly more sensitive in the detection of HSIL and cancer (McNemar test, P<0.001). Adjudication of cases in which the ThinPrep and smear diagnoses disagreed, using the final case diagnoses and the HPV DNA test results as reference standards, suggested that the ThinPrep method was detecting additional true SIL as opposed to false-positives. CONCLUSIONS: In a population-based study of high risk women, ThinPrep cytology demonstrated significantly increased sensitivity for detecting HSIL and carcinoma, with a concurrent significant increase in colposcopy referrals.

Evaluation of the patient with blunt chest trauma: an evidence based approach.

The patient who has sustained blunt trauma to the chest can present a diagnostic challenge to the emergency physician. There are several diagnostic modalities available for treating life-threatening injuries to these patients. The authors review published studies to support the use of these tests in diagnosing injuries from blunt thoracic trauma. The article focuses chiefly on two current areas of controversy, the diagnosis of blunt aortic and blunt myocardial injury. Finally, the authors make recommendations for the use of various tests based on the available evidence.

Cervicography screening for cervical cancer among 8460 women in a high-risk population.

OBJECTIVE: Cervicography was evaluated as a primary screening method for cervical cancer. STUDY DESIGN: Cervigrams of 8460 women were taken on enrollment into a population-based study of cervical neoplasia. Cervicography results were compared with a referent diagnosis determined by histologic analysis and 3 cytologic tests, and with the performance of conventional cytologic evaluation. RESULTS: Cervicography identified all 11 cancers, whereas cytologic testing missed 1. Cervicography yielded sensitivities for detecting high-grade squamous intraepithelial lesions or cancer of 49.3% overall (specificity, 95.0%), 54.6% in women younger than 50 years of age, and 26.9% in women 50 years of age and older. Cytologic testing yielded sensitivities for detecting high-grade squamous intraepithelial lesions or cancer of 77.2% overall (specificity, 94. 2%), 75.5% in women younger than 50 years of age, and 84.6% in women 50 years of age and older. CONCLUSIONS: Cytologic testing performed better than cervicography for the detection of high-grade squamous intraepithelial lesions. Cervicography performed marginally better than cytologic testing for the detection of invasive cervical cancer. Cervicography is not recommended for postmenopausal women.

A prospective study of biopsy-confirmed cervical intraepithelial neoplasia grade 1: colposcopic, cytological, and virological risk factors for progression.

OBJECTIVES: The objective of this prospective study of histologically confirmed cervical intraepithelial neoplasia (CIN) (including equivocal CIN1) was to determine risk factors for progression to histologically confirmed CIN3, particularly human papillomavirus (HPV) types and cofactors. We postulated that HPV DNA positivity would be a strong, prospective risk factor for progression. MATERIALS AND METHODS: Possible participants were referred with an abnormal cytological diagnosis of CIN1 or lower-grade disease or external genital warts. Women with histologically confirmed CIN1 (including koilocytotic atypia) or equivocal CIN1 were eligible for follow-up. Of these, 163 women were assessed every 3 months (if a lesion were present) or every 6 months (if a lesion regressed colposcopically during the course of the study), for up to 52 months. Progression was defined histologically, whereas persistence and regression were defined by combined cytological, colposcopic, and histological assessments. Subjects who progressed to a biopsy-confirmed CIN3 or who developed a lesion that was clinically unsafe to follow up (i.e., because of movement into the endocervical canal), were removed from the study and were treated. RESULTS: A total of 237 patients were evaluated as possible participants. The 74 exclusions at enrollment included 33 patients who had an entry diagnosis of CIN2 to CIN3 or who had lesions that were otherwise already unsafe to follow up, 39 who did not have a lesion on colposcopically directed biopsy, and 2 who were immediately noncompliant. Among the remaining 163 participants, the overall progression rate to histologically confirmed CIN3 was 8%, the persistence rate was 49%, and the regression rate was 43%. All progressions occurred among women who were HPV DNA-positive and had colposcopically immature abnormal transformation zones.

Performance of a semiautomated Papanicolaou smear screening system: results of a population-based study conducted in Guanacaste, Costa Rica.

BACKGROUND: Automated cytology devices have utility in quality assurance applications, but the effectiveness of these devices in primary screening is unknown. METHODS: Enrollment smears obtained from 7323 women participating in a population-based study sponsored by the National Cancer Institute were screened manually in Costa Rica and then evaluated independently in the U.S. with the PAPNET system (Neuromedical Systems, Inc., Suffern, NY), a semiautomated, neural network-based device. Smears with abnormal PAPNET images were microscopically rescreened and then diagnosed by a U.S. cytopathologist. ThinPrep slides (Cytyc Corporation, Boxborough, MA), prepared from rinses of the cytologic sampler, and cervigrams (National Testing Laboratories, Fenton, MO) were also evaluated. Women with any abnormal cytologic diagnosis or a positive cervigram were referred for colposcopy with biopsy and definitive therapy if indicated. RESULTS: Based on the U.S. cytotechnologist's review of the PAPNET images, 1017 (13.9%) of 7323 smears were selected for manual screening, resulting in the selection of 492 (6.7%) possibly abnormal slides for referral to the U.S. pathologist. Ultimately, 312 smears (4.3% of the total) were diagnosed as containing squamous cells of undetermined significance or a more severe abnormality (> or =ASCUS), resulting, hypothetically, in the referral of 66.5% of women with a final diagnosis of a squamous intraepithelial lesion or a more severe abnormality (> or =SIL) and 86.0% of patients with > or =high grade SIL. Conventional microscopic screening performed in Costa Rica resulted in the hypothetical referral of 6.5% of patients with > or =ASCUS for colposcopy, including 69.5% of patients with > or =SIL and 79.8% of those with > or =high grade SIL. CONCLUSIONS: In this study, PAPNET-assisted cytologic screening accurately identified smears obtained from women with high grade SIL or carcinoma. Determination of the clinical cost-effectiveness of PAPNET-assisted screening in routine practice awaits future study.

Safety and efficacy of 0.5% podofilox gel in the treatment of anogenital warts.

OBJECTIVE: To determine the safety and efficacy of a new gel formulation of podofilox in the treatment of anogenital warts. DESIGN: Double-blind, randomized, multicenter, vehicle-controlled investigation. SETTING: Private dermatology practices, university clinics (dermatology, gynecology, and infectious diseases), and contract research organizations. PATIENTS: Three hundred twenty-six patients with anogenital warts. MAIN OUTCOME MEASURE: Number of patients with clearing of all treated warts (treatment success). RESULTS: The 0.5% podofilox gel was significantly better than vehicle gel for successfully eliminating and reducing the number and size of anogenital warts. In the intent-to-treat population, 62 (37.1%) of 167 patients treated with 0.5% podofilox gel had complete clearing of the treated areas (treatment successes) compared with 2 (2.3%) of 86 patients who had clearing of warts with the vehicle gel (P < .001) after 4 weeks. Nineteen additional patients treated with 0.5% podofilox gel and 2 patients treated with vehicle gel had clearing of warts with continued treatment up to 8 weeks. After 8 weeks, 35.9% of the baseline anogenital warts treated with 0.5% podofilox gel remained; this was significantly fewer than in the vehicle-treated group (88.4% of the baseline number) (P = .001). The 0.5% podofilox gel was generally well tolerated, with predominantly mild or moderate local adverse reactions occurring in the majority of patients. Only 7 patients (3.2%), all receiving 0.5% podofilox gel, discontinued study treatment because of drug-related local reactions. CONCLUSIONS: The results demonstrated that 0.5% podofilox gel is safe and significantly more effective than vehicle gel in the treatment of anogenital warts.

Colposcopy Quality Control: Establishing Colposcopy Criterion Standards for the National Cancer Institute ALTS Trial Using Cervigrams.

OBJECTIVES: The colposcopy quality control (QC) group of the Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesions (ASCUS/ LSIL) Triage Study (ALTS) monitors colposcopists at four clinical centers by direct observation and indirectly by assessment of digitized computer colposcopic images transferred nightly by modem. The purpose of this preclinical study was to determine the agreement among colposcopy QC monitors' colposcopic impressions and biopsy site placement through evaluation of cervical photographic images. MATERIALS AND METHODS: A nonparticipant selected 100 Cervigram slides representing four pathologically confirmed categories: cervical intraepihelial neoplasia 1(CIN), CIN2 and CIN3, normal, and cancer. our colposcopy QC monitors and two certified Cervigram evaluators independently interpreted the images for colpocopic impression on two separate occasions. Measures of agreement were calculated for intraobserver, pairwise interobserver, and observer versus histological diagnoses. Participants also indicated the most severe biopsy site by marking an χ on a 4 × 6-inch color print duplication. Mean distances between biopsy site annotations for each pair of evaluators were calculated. RESULTS: The ALTS observer agreement with histology ranged from 75.3% (K = .66) to 47.4% (K = .36) for the first evaluation and 71.1 % (K = .63) to 50.5% (K = .38) for the second evaluation. ALTS interobserver agreement varied between 71 % and 57% for the first interpretation and 76% and I2% for the second evaluation. ALTS intraobserver agreement varied from 86% (K = .86) to 68.0% (K = .60). The mean listances between biopsy site annotations for each pair of ALTS observers varied from 0.99 ± 0.93 mm to 1.44 ± 1.19 nm. CONCLUSIONS: The ALTS colposcopy QC monitors achieved poor to good observer agreement with histology, fair to excellent interobserver agreement, and good to excellent intraobserver agreement in assessing the severity of cervical images. These levels of agreement are similar to many reported by pathologists for cervical cytology and histology interpretations. Monitors also demonstrated a very narrow variation of distance (< 2 mm) for ideal biopsy site placement.

Quality indicators for out-of-hospital emergency medical services: the paramedics' perspective.

OBJECTIVE: Out-of-hospital emergency medical services (EMS) need relevant and measurable indicators of quality. Those front-line workers who provide service directly to the customer are integral to the process of defining quality. The authors' objective was to obtain from paramedics, the front-line workers in the EMS system, their perspective on quality of care. METHODS: During regularly scheduled education sessions, 102 of the 140 field paramedics from a large municipal EMS system attended a presentation on total quality management. The paramedics were then assigned to focus groups and asked to identify quality indicators and provide recommendations for how they should be measured. RESULTS: Eighteen different quality indicators were identified. In addition, the paramedics suggested 17 ways to measure these proposed quality indicators. CONCLUSIONS: From the perspective of the study participants, indicators of the quality of out-of-hospital care differ from many used in traditional EMS quality assurance programs. Future studies should investigate the applicability of these indicators to the total quality management of EMS systems.

Clinical manifestations and natural history of genital human papillomavirus infections.

Over the past decade, the ever-increasing volume of evidence implicating HPV types in genital neoplasia has stimulated much research interest into all aspects of the biology of this interesting group of viruses. This research has led to the identification of growing heterogeneity of HPV types. It is not surprising, therefore, that the clinical profile of disease associated with genital HPV types is much broader than previously recognized. Knowledge of this clinical spectrum is mandatory to the understanding of the possible role of specific HPV types in human carcinogenesis.