Aptima HPV E6/E7 mRNA test is as sensitive as Hybrid Capture 2 Assay but more specific at detecting cervical precancer and cancer.

Detection of human papillomavirus (HPV) E6/E7 oncogene expression may be more predictive of cervical cancer risk than testing for HPV DNA. The Aptima HPV test (Gen-Probe) detects E6/E7 mRNA of 14 oncogenic types. Its clinical performance was compared with that of the Hybrid Capture 2 DNA test (HC2; Qiagen) in women referred for colposcopy and those routinely screened. Aptima was also compared with the PreTect HPV-Proofer E6/E7 mRNA assay (Proofer; Norchip) in the referral population. Cervical specimens collected in PreservCyt (Hologic Inc.) were processed for HPV detection and genotyping with the Linear Array (LA) method (Roche Molecular Diagnostics, Laval, Quebec, Canada). Histology-confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN 2+) served as the disease endpoint. On the basis of 1,418 referral cases (CIN 2+, n = 401), the sensitivity of Aptima was 96.3% (95% confidence interval [CI], 94.4, 98.2), whereas it was 94.3% (95% CI, 92.0, 96.6) for HC2. The specificities were 43.2% (95% CI, 40.2, 46.2) and 38.7% (95% CI, 35.7, 41.7), respectively (P < 0.05). In 1,373 women undergoing routine screening (CIN 2+, n = 7), both Aptima and HC2 showed 100% sensitivity, and the specificities were 88.3% (95% CI, 86.6, 90.0) and 85.3% (95% CI, 83.5, 87.3), respectively (P < 0.05); for women ≥ 30 years of age (n = 845), the specificities were 93.9% (95% CI, 92.3, 95.5) and 92.1% (95% CI, 90.3, 93.9), respectively (P < 0.05). On the basis of 818 referral cases (CIN 2+, n = 235), the sensitivity of Aptima was 94.9% (95% CI, 92.1, 97.7) and that of Proofer was 79.1% (95% CI, 73.9, 84.3), and the specificities were 45.8% (95% CI, 41.8, 49.8) and 75.1% (95% CI, 71.6, 78.6), respectively (P < 0.05). Both Aptima and Proofer showed a higher degree of agreement with LA genotyping than HC2. In conclusion, the Aptima test is as sensitive as HC2 but more specific for detecting CIN 2+ and can serve as a reliable test for both primary cervical cancer screening and the triage of borderline cytological abnormalities.

Clinical performance of the PreTect HPV-Proofer E6/E7 mRNA assay in comparison with that of the Hybrid Capture 2 test for identification of women at risk of cervical cancer.

Human papillomavirus (HPV) DNA testing has a higher clinical sensitivity than cytology for the detection of high-grade cervical intraepithelial neoplasia or worse (CIN 2+). However, an improvement in specificity would be desirable. As malignant transformation is induced by HPV E6/E7 oncogenes, detection of E6/E7 oncogene activity may improve specificity and be more predictive of cervical cancer risk. The PreTect HPV-Proofer assay (Proofer; Norchip) detects E6/E7 mRNA transcripts from HPV types 16, 18, 31, 33, and 45 with simultaneous genotype-specific identification. The clinical performance of this assay was assessed in a cross-sectional study of women referred for colposcopy in comparison with the Hybrid Capture 2 (HC2; Qiagen) test, which detects DNA of 13 high-risk oncogenic HPV types collectively. Cervical specimens were collected in PreservCyt, and cytology was performed using the ThinPrep method (Hologic). The samples were processed for HPV detection with Proofer and HC2 and genotyping with the Linear Array method (Roche Molecular Systems). Histology-confirmed CIN 2+ served as the disease endpoint to assess the clinical performance of the tests. A total of 1,551 women were studied, and of these, 402 (25.9%) were diagnosed with CIN 2+ on histology. The Proofer assay showed a sensitivity of 78.1% (95% confidence interval [CI], 74.1 to 82.1) versus 95.8% (95% CI, 93.8 to 97.8) for HC2 (P < 0.05) and a specificity of 75.5% (95% CI, 73.0 to 78.0) versus 39.6% (95% CI, 36.8 to 42.4), respectively (P < 0.05). The lower sensitivity and higher specificity of Proofer for detection of CIN 2+ can be attributed to the fact that this test detects the expression of E6/E7 genes beyond a threshold from a limited number of oncogenic HPV types. In conclusion, Proofer is more specific than HC2 in identifying women with CIN 2+ but has a lower sensitivity.

Randomized trial of oral misoprostol before endometrial biopsy.

OBJECTIVE: To determine if the use of oral misoprostol in women undergoing endometrial biopsy reduces procedural discomfort. METHODS: Women undergoing endometrial biopsy were randomized to receive either 400 microg misoprostol or a vitamin B6 placebo orally 12 hours prior to the procedure, and were stratified based on menopausal status. The primary outcome was procedural discomfort on a visual analogue scale (0-10). Secondary outcomes included the need to dilate the cervix or use a tenaculum, and side effects. Subgroup analyses were planned for premenopausal and postmenopausal women separately. Sample size calculation was based on detecting a 50% reduction in pain, with alpha = 0.05 and beta = 0.10, in the premenopausal group. RESULTS: A total of 72 women (49 premenopausal and 23 postmenopausal) were enrolled; 35 received misoprostol (23 premenopausal and 12 postmenopausal) and 37 received placebo (26 premenopausal and 11 postmenopausal). There were no significant differences in procedural discomfort (misoprostol vs. placebo 5.8 +/- 2.9 vs. 5.5 +/- 3.2, P = 0.77; premenopausal women 4.9 +/- 3.3 vs. 5.1 +/- 3.1, P = 0.85; postmenopausal women 7.1 +/- 1.9 vs. 7.1 +/- 2.3, P = 0.99), need to dilate the cervix (6.1% vs. 5.6%, P = 0.93) or use a tenaculum (44.1% vs. 48.6%, P = 0.70). Significantly more women in the misoprostol group experienced nausea (31.4% vs. 2.7%, P = 0.001), diarrhea (20.0% vs. 2.7%, P = 0.02), abdominal pain (22.9% vs. 5.4%, P = 0.03), menstrual-like cramping (42.9% vs. 2.7%, P < 0.001) and vaginal bleeding (11.4% vs. 0%, P = 0.03). CONCLUSION: The use of 400 microg oral misoprostol 12 hours prior to endometrial biopsy did not reduce procedural discomfort and was associated with more side effects than use of placebo. This finding was noted in all women as well as among subgroups of premenopausal and postmenopausal women.

Guidelines for operative vaginal birth.

OBJECTIVE: To provide guidelines for operative vaginal birth in the management of the second stage of labour. OPTIONS: Non-operative techniques, episiotomy, and Caesarean section are compared to operative vaginal birth. outcome: Reduced fetal and maternal morbidity and mortality. EVIDENCE: MEDLINE and Cochrane databases were searched using the key words 'vacuum' and 'birth' as well as 'forceps' and 'birth' for literature published in English from January 1970 to June 2004. The level of evidence and quality of recommendations made are described using the Evaluation of Evidence from the Canadian Task Force on the Periodic Health Examination. RECOMMENDATIONS: 1. Non-operative interventions such as one-to-one support, partogram use, oxytocin use, and delayed pushing in women using epidurals will decrease need for operative birth. (I-A) 2. Manual rotation may be used alone or in conjunction with instrumental birth with little or no increased risk to the pregnant woman or to the fetus. (III-B) 3. Routine episiotomy is not necessary for an assisted vaginal birth. (II-1E) 4. When operative intervention in the second stage of labour is required, the options, risks, and benefits of vacuum, forceps, and Caesarean section must be considered. The choice of intervention needs to be individualized, as one is not clearly safer or more effective than the other. (II-B) 5. Failure of the chosen method, vacuum and/or forceps, to achieve delivery of the fetus in a reasonable time should be considered an indication for abandonment of the method. (III-C) 6. Adequate clinical experience and appropriate training of the operator are essential to the safe performance of operative deliveries. Hospital credentialing boards should grant privileges for performing these techniques only to an appropriately trained individual who demonstrates adequate skills. (III-C). VALIDATION: The Clinical Practice Obstetrics Committee and Executive and Council of the Society of Obstetricians and Gynaecologists of Canada approved these guidelines.

Exercise in pregnancy and the postpartum period.

OBJECTIVE: To design Canadian guidelines advising obstetric care providers of the maternal, fetal, and neonatal implications of aerobic and strength-conditioning exercises in pregnancy. OUTCOMES: Knowledge of the impact of exercise on maternal, fetal, and neonatal morbidity, and of the maternal measures of fitness. EVIDENCE: MEDLINE search from 1966 to 2002 for English-language articles related to studies of maternal aerobic and strength conditioning in a previously sedentary population, maternal aerobic and strength conditioning in a previously active population, impact of aerobic and strength conditioning on early and late pregnancy outcomes, and impact of aerobic and strength conditioning on neonatal outcomes, as well as for review articles and meta-analyses related to exercise in pregnancy. VALUES: The evidence collected was reviewed by the Society of Obstetricians and Gynaecologists of Canada (SOGC Clinical Practice Obstetrics Committee) with representation from the Canadian Society for Exercise Physiology, and quantified using the evaluation of evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS: 1. All women without contraindications should be encouraged to participate in aerobic and strength-conditioning exercises as part of a healthy lifestyle during their pregnancy. (II-1,2B) 2. Reasonable goals of aerobic conditioning in pregnancy should be to maintain a good fitness level throughout pregnancy without trying to reach peak fitness or train for an athletic competition. (II-1,2C) 3. Women should choose activities that will minimize the risk of loss of balance and fetal trauma. (III-C) 4. Women should be advised that adverse pregnancy or neonatal outcomes are not increased for exercising women. (II-1,2B) 5. Initiation of pelvic floor exercises in the immediate postpartum period may reduce the risk of future urinary incontinence. (II-1C) 6. Women should be advised that moderate exercise during lactation does not affect the quantity or composition of breast milk or impact infant growth. (I-A) VALIDATION: This guideline has been approved by the SOGC Clinical Practice Obstetrics Committee, the Executive and Council of SOGC, and the Board of Directors of the Canadian Society for Exercise Physiology. SPONSORS: This guideline has been jointly sponsored by the Society of Obstetricians and Gynaecologists of Canada and the Canadian Society for Exercise Physiology.

Bereavement support for women and their families after stillbirth.

OBJECTIVES: (1) To heighten awareness of the grieving process of the mother and her family experiencing the death of a baby; (2) to offer suggestions to health-care providers of the type of support that will achieve optimal grief resolution. OPTIONS: Early, late, or no interventions for women and families who experienced stillbirths. OUTCOME: Success of health-care providers in preventing, recognizing, and treating psychological problems in the bereaved parents and families, and also in helping these families to build meaningful experiences and positive memories from their loss. EVIDENCE: English-language articles and their references on grief and bereavement after perinatal death, through a search of MEDLINE, the Cochrane Library, and publications of other national bodies including the Canadian Paediatric Society, and the American College of Obstetricians and Gynecologists.

The management of nausea and vomiting of pregnancy.

OBJECTIVES: To review the evidence-based management of nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum. EVIDENCE: MEDLINE and Cochrane database searches were performed using the medical subject headings (MeSH) of treatment, nausea, vomiting, pregnancy, and hyperemesis gravidarum. The quality of evidence reported in these guidelines has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam. BENEFITS: NVP has a profound effect on women's health and quality of life during pregnancy, as well as a financial impact on the health care system, and its early recognition and management are recommended. (III-B) COST: Costs, including hospitalizations, additional office visits, and time lost from work, may be reduced if NVP is treated early.

Hemorrhagic shock.

OBJECTIVE: To review the clinical aspects of hemorrhagic shock and provide recommendations for therapy. OPTIONS: Early recognition of hemorrhagic shock and prompt systematic intervention will help avoid poor outcomes. OUTCOMES: Establish guidelines to assist in early recognition of hemorrhagic shock and to conduct resuscitation in an organized and evidence-based manner. EVIDENCE: Medline references were sought using the MeSH term "hemorrhagic shock." All articles published in the disciplines of obstetrics and gynaecology, surgery, trauma, critical care, anesthesia, pharmacology, and hematology between 1 January 1990 and 31 August 2000 were reviewed, as well as core textbooks from these fields. Selected references from these articles and book chapters were also obtained and reviewed. The level of evidence has been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination. RECOMMENDATIONS: 1. Clinicians should be familiar with the clinical signs of hemorrhagic shock. (III-B) 2. Clinicians should be familiar with the stages of hemorrhagic shock. (III-B) 3. Clinicians should assess each woman's risk for hemorrhagic shock and prepare for the procedure accordingly. (III-B) 4. Resuscitation from hemorrhagic shock should include adequate oxygenation. (II-3A) 5. Resuscitation from hemorrhagic shock should include restoration of circulating volume by placement of two large-bore IVs, and rapid infusion of a balanced crystalloid solution. (I-A) 6. Isotonic crystalloid or colloid solutions can be used for volume replacement in hemorrhagic shock (I-B). There is no place for hypotonic dextrose solutions in the management of hemorrhagic shock (I-E). 7. Blood component transfusion is indicated when deficiencies have been documented by clinical assessment or hematological investigations (II-2B). They should be warmed and infused through filtered lines with normal saline, free of additives and drugs (II-3B). 8. Vasoactive agents are rarely indicated in the management of hemorrhagic shock and should be considered only when volume replacement is complete, hemorrhage is arrested, and hypotension continues. They should be administered in a critical care setting with the assistance of a multidisciplinary team. (III-B) 9. Appropriate resuscitation requires ongoing evaluation of response to therapy, including clinical evaluation, and hematological, biochemical, and metabolic assessments. (III-B) 10. In hemorrhagic shock, prompt recognition and arrest of the source of hemorrhage, while implementing resuscitative measures, is recommended. (III-B)VALIDATION: These guidelines have been reviewed by the Clinical Practice Obstetrics Committee and approved by Executive and Council of the Society of Obstetricians and Gynaecologists of Canada. SPONSORS: The Society of Obstetricians and Gynaecologists of Canada.