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Background: Neonatal research, particularly neonatal emergency research is a challenging area, notably in relation to obtaining valid prospective informed consent. The aim of this study is to determine parental perceptions of the consent process involved in performing research in newborn care, to explore methods used to obtain consent and their acceptability to parents.Methods: A parental questionnaire was developed that examined attitudes towards research and hypothetical research studies, in which the acceptability of various methods of consent was examined (informed, waived, deferred). These research scenarios were of varying time sensitivity and perceived risk level. The study setting was an Irish maternity hospital.Results: There were 600 responses to the questionnaire. In 93% of cases, parents felt that their involvement in the consent process was essential. In emergency situations, 52% felt full prospective informed consent was necessary; however, almost 28% of parents would feel pressure to consent. Most (75%) parents would prefer to be approached to discuss neonatal research studies antenatally, irrespective of study type and 40% of parents felt that neonates involved in research studies received overall better care. Acceptability of deferred consent was greater than waived, and was highest for the more emergency-based scenarios presented.Discussion: Parents feel that they should play a central role in research involving their children. There were differences in the acceptability of various consent methods with strongest agreement for informed consent and lowest agreement for waived consent. Parents were more willing to accede to deferred consent in the cardiopulmonary resuscitation scenario study. These findings provide useful insights to consent strategies in future newborn research studies. [ABSTRACT FROM AUTHOR]

Objective: To estimate the efficacy of a fluid-based, thin-layer preparation (TP) compared with the conventional Pap (CP) test to detect biopsy confirmed precancerous cervical lesions.Materials and Methods: A total of 10,226 evaluable patients at 10 separate clinical sites were screened for cervical abnormalities using the TP (ThinPrep pap test; Cytyc Corporation, Boxborough, MA). Results were compared with an historical control cohort of 20,918 patients from a similar patient population and with a similar patient profile who had received CP screening.Results: The TP significantly increased the detection rate of high-grade squamous intraepithelial lesion and more severe (HSIL+) cytologic results as compared with the CP smear. Overall, the TP method yielded a 59.7% increase in the detection of HSIL+ compared with the CP smear. Overall, the TP method yielded a 59.7% increase in the detection of HSIL+ compared with the conventional method (3.9% vs. 2.4%; p < .001). There was also a significant increase in the detection of low-grade squamous intraepithelial lesions with TP (p < .01). The rates of cancer, atypical squamous cells of undetermined significance, and atypical glandular cells of undetermined significance were similar for the TP and CP groups.Conclusions: The overall cytologic detection of HSIL and low-grade squamous intraepithelial lesions with the TP method was significantly increased compared with a control group screened with the CP method. Histologic confirmation showed increased detection, not an increased false-positive cytologic interpretation. [ABSTRACT FROM AUTHOR]

Objective: To determine practice patterns of the American Society for Colposcopy and Cervical Pathology (ASCCP) 2000 Biennial Meeting participants for management of women with atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGUS).Materials and Methods: A three-page survey was developed to query participants about their standard practices for managing atypical squamous cells and atypical glandular cells on Pap tests; use of human papillomavirus testing; and use of vaginal estrogen cream in postmenopausal women before follow-up.Results: There were 217 completed surveys (47.0% response rate). Responses of 194 qualified surveys are presented here. For women with first-time ASCUS (unqualified) and no previous history of cervical intraepithelial neoplasia (CIN), 16.4% of respondents would perform colposcopy. For ASCUS (favor squamous intraepithelial lesion [SIL]), a significantly higher percent, 74.9%, would proceed immediately to colposcopy (p < .001). For ASCUS (unqualified or favor SIL) in a woman with a previous history of CIN, 82.7% and 95.5% would perform colposcopy, respectively (p < .001). For a patient with AGUS, 97.5% would perform colposcopy (with or without endocervical curettage or endometrial biopsy). Human papillomavirus testing was seldom used in the management of ASCUS (10.4%) and AGUS (7.8%).Conclusions: Participants at the 2000 ASCCP Biennial Meeting made clear distinctions between ASCUS and AGUS in managing women with abnormalities on Pap, and management was consistent with guidelines published by the ASCCP, American College of Obstetricians and Gynecologists, and the National Cancer Institute. [ABSTRACT FROM AUTHOR]

PURPOSE: To compare cytology with cervicography in HIV-infected and uninfected adolescent females. METHODS: At the time of analysis, 334 girls aged 13-19 years from 13 U.S. cities were participating in a prospective study of HIV infection. All subjects had cytology and a Cervigram (cervicography) performed at two consecutive visits 6 months apart, referred to as visit (V) 1 and 2. Cervigrams were sent to the parent company for diagnosis and were categorized as: 'negative' or 'positive' (compatible with low-grade or high-grade squamous intraepithelial lesions [SIL]). Cytology was considered abnormal if the subject had SIL at either V1 or V2. Sensitivity, specificity, and positive predictive value (PPV) of the Cervigram were calculated compared with repeat Papanicolaou (Pap) smears. RESULTS: Two consecutive adequate Pap smears were available for analysis in 200 adolescents; 51% (95% CI, 43-59) of the 142 HIV-positive youth and 19% (95% CI, 9-29) of the 58 HIV-negative youth had SIL on at least one Pap smear (p < .001). A positive Cervigram was observed in 44% (95% CI, 36-53) of the HIV-infected group and 29% (95% CI, 17-41) of the HIV-uninfected group (p =.06). For the HIV-infected group, the sensitivity, specificity, and PPV of the Cervigram to detect SIL were 58% (95% CI, 45-71), 69% (95%CI, 57-80), and 64% (95%CI, 52-77), respectively. For the HIV-uninfected group, the sensitivity, specificity, and PPV were 64% (95% CI, 31-89), 80% (95% CI, 65-90), and 44% (95% CI, 19-68), respectively. The combined sensitivity, using both the Pap smear and Cervigram result from V1 to detect SIL, was 82% (95% CI, 71-91 for HIV+ and 48-98 for HIV-) in both groups. However, the PPV based the performance of the Cervigram in Pap smear-negative women as 33% (95% CI, 17-53) and 15% (95% CI, 2-45) for the HIV-infected and uninfected group, respectively (p = not significant [ns]). CONCLUSIONS: Although the sensitivity of a single Pap smear increased significantly when the Cervigram was used as an adjunct, the low PPV in both HIV-infected and uninfected groups, suggests that cervicography has a limited utility for precancer and cervical cancer screening in high-risk adolescent populations. Copyright Society for Adolescent Medicine, 2003 [ABSTRACT FROM AUTHOR]

Background: Anal cancers are thought to arise from squamous intraepithelial lesions in the anal canal, and women infected with human immunodeficiency virus-1 (HIV) may be at higher risk of anal cancer. Our aim was to determine the prevalence of human papillomavirus (HPV)-related abnormalities of the anal canal in women and to characterize risk factors for these lesions.Methods: We evaluated HPV-related abnormalities in 251 HIV-positive and in 68 HIV-negative women. We completed physical examinations and obtained questionnaire data on medical history and relevant sexual practices. Univariate and adjusted relative risks (RRs) and 95% confidence intervals (CIs) were computed using the Mantel-Haenszel procedure and regression techniques. All statistical tests were two-sided.Results: Abnormal anal cytology, including atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, or high-grade squamous intraepithelial lesions (HSILs), was diagnosed in 26% of HIV-positive and in 8% of HIV-negative women. HSILs were detected by histology or cytology in 6% of HIV-positive and in 2% of HIV-negative women. HIV-positive women showed increased risk of anal disease as the CD4 count decreased (P<.0001) and as the plasma HIV RNA viral load increased (P =.02). HIV-positive women with abnormal cervical cytology had an increased risk of abnormal anal cytology at the same visit (RR = 2.2; 95% CI = 1.4 to 3.3). Abnormal anal cytology in HIV-positive women was associated with anal HPV RNA detected by the polymerase chain reaction and by a nonamplification-based test (RR = 4.3; 95% CI = 1.6 to 11). In a multivariate analysis, the history of anal intercourse and concurrent abnormal cervical cytology also were statistically significantly (P =.05) associated with abnormal anal cytology.Conclusions: HIV-positive women had a higher risk of abnormal anal cytology than did HIV-negative women with high-risk lifestyle factors. These data provide strong support for anoscopic and histologic assessment and careful follow-up of women with abnormal anal lesions. [ABSTRACT FROM AUTHOR]

Objectives: To determine interrater variability in classifying cervical biopsies from women with human immunodeficiency virus (HIV).Materials and Methods: Cervical biopsies performed on women participating in the Women's Interagency HIV Study (WIHS) were read at the six participating sites. A 10% random sample was retrieved and reviewed using standardized terminology by pathologists with a special interest in gynecologic pathology. Results were compared with kappa values and Mantel-Haentzel tests.Results: Biopsies from 288 HIV-seropositive and 24 HIV-seronegative women were reviewed. The weighted kappa value of 0.67 indicated moderate to strong agreement between original and review diagnoses, with a range of 0.54 to 0.84 across sites. No cancers were identified. Significantly more specimens showing cervical intraepithelial neoplasia (CIN) grade 2 or 3 were identified by review pathologists (p = .02). CIN2 or CIN3 was graded less severely by local pathologists in 18 (51%) of 35 cases, all from HIV-seropositive women. Local pathologists' diagnoses of CIN2 or CIN3 were downgraded by reviewers in 4 of 21 cases (19%). Discrepancies were more common among women with lower CD4 lymphocyte counts.Conclusions: Although discrepancies occur, interrater correlation in the interpretation of cervical biopsies from women with HIV is moderate to strong. [ABSTRACT FROM AUTHOR]

Objective: Our intent was to compare the management of patients with atypical squamous cells of undetermined significance on cytologic screening at an academic center to published guidelines.Study Design: We reviewed the management of 223 atypical squamous cells of undetermined significance cervical smears. Patients with a history of dysplasia were excluded. The time interval to and nature of follow-up testing was determined, and the influence of atypical squamous cells of undetermined significance qualifiers and provider specialty analyzed.Results: Initial follow-up consisted of repeat cytologic examination alone in 94% of cases. Of patients with follow-up, 29% were retested within 2 months and 68% within 4 months. No conclusive differences in management were found by qualifier type or by provider specialty. Subsequent high-grade dysplasia was found in 2.6% of patients.Conclusions: A discrepancy exists between published guidelines and actual management of patients with atypical squamous cells of undetermined significance smears at this medical center. Patients often undergo follow-up testing at shorter intervals than those suggested despite a low likelihood of finding high-grade disease. [ABSTRACT FROM AUTHOR]

Context: Low-grade squamous intraepithelial lesions (LSILs) have been described as a benign cytological consequence of active human papillomavirus (HPV) replication. Several studies have reported that certain behavioral and biological risks exist for LSIL, suggesting that HPV alone is not sufficient for the development of LSIL. However, because most of these studies have been cross-sectional, it is not known whether behavioral and biological risks are simply risks for HPV infection itself.Objective: To prospectively examine risks of incident HPV infection in HPV-negative females and of incident LSIL development in females with HPV infection.Design: Prospective cohort study conducted between 1990-2000, with a median follow-up of 50 months.Setting and Participants: Females aged 13 to 21 years who attended 2 family planning clinics in the San Francisco bay area; 496 had prevalent HPV infection and 105 were HPV-negative.Main Outcome Measure: Incident development of HPV infection and LSIL, analyzed by various demographic, behavioral, and clinical risk factors.Results: Fifty-four incident HPV infections occurred in the 105 females who were HPV-negative at study entry (median duration of follow-up for those who remained HPV-negative was 26 months). Multivariable analysis showed that risks of HPV included sexual behavior (relative hazard [RH], 10.10; 95% confidence interval [CI], 3.24-31.50 per new partner per month), history of herpes simplex virus (RH, 3.54; 95% CI, 1.37-9.10), and history of vulvar warts (RH, 2.73; 95% CI, 1.27-5.87). Current use of oral contraceptives had a significantly protective effect (RH, 0.49; 95% CI, 0.28-0.86). Among the 496 individuals who were HPV-positive at baseline or in follow-up, there were 109 incident cases of LSIL during the follow-up interval, with a median follow-up time of 60 months for those who never developed LSIL. Human papillomavirus infection was the most significant risk factor for development of LSIL. The multivariable model showed the following risks for LSIL: HPV infection for less than 1 year (RH, 7.40; 95% CI, 4.74-11.57); HPV infection for 1 to 2 years (RH, 10.27; 95% CI, 5.64-18.69); HPV infection for 2 to 3 years (RH, 6.11; 95% CI, 1.86-20.06); and daily cigarette smoking (RH, 1.67; 95% CI, 1.12-2.48).Conclusion: Our results indicate distinct risks for HPV and LSIL. In addition, most women with HPV infection in our study did not develop LSIL within a median follow-up period of 60 months. These findings underscore the hypothesis that certain biological risks thought to be associated with LSIL are, in fact, risks for acquisition of HPV. Cigarette smoking was a risk specific to LSIL, supporting the role of tobacco in neoplastic development. [ABSTRACT FROM AUTHOR]

Background: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.Methods: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer.Results: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test).Conclusions: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.). [ABSTRACT FROM AUTHOR]