N JUNE 8, 2006, THE FOOD and Drug Administration (FDA) licensed the quadrivalent human papillomavirus recombinant vaccine (qHPV) (Gardasil; Merck & Co, Inc, Whitehouse Station, New Jersey) for females aged 9 to 26 years to prevent infection with genital human papillomavirus (HPV) types 6, 11, 16, and 18. 1 Later that month, the Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination of females aged 11 to 12 years with 3 doses of qHPV and catch-up vaccination for females aged 13 to 26 years. Doses are administered intramuscularly on a schedule of 0, 2, and 6 months. 2 The viruses HPV-16 and HPV-18 can cause cervical cancer, other anogenital cancers, and precancerous or dysplastic lesions and are responsible for about 70% of cervical cancers worldwide. 3 The viruses HPV-6 and HPV-11 are the most common causes of genital warts. Prior to licensure, clinical trials were conducted in more than 21 000 women. Vaccination with qHPV was 90% to 100% effective in preventing precancerous cervical, vaginal, and vulvar lesions and genital warts caused by infection with the relevant HPV types (6, 11, 16, or 18) in women aged 15 to 26 years who were uninfected prior to vaccination. 4,5 Additional immunogenicity and safety studies in 9-to 15-year-See also pp 781 and 795.

Purpose To assess case-only designs for surveillance with administrative databases. Methods We reviewed literature on two designs that are observational analogs to crossover experiments: the self-controlled case series (SCCS) and the case-crossover (CCO) design. Results SCCS views the 'experiment' prospectively, comparing outcome risks in windows with different exposures. CCO retrospectively compares exposure frequencies in case and control windows. The main strength of case-only designs is they entail self-controlled analyses that eliminate confounding and selection bias by time-invariant characteristics not recorded in healthcare databases. They also protect privacy and are computationally efficient, as they require fewer subjects and variables. They are better than cohort designs for investigating transient effects of accurately recorded preventive agents, for example, vaccines. They are problematic if timing of self-administration is sporadic and dissociated from dispensing times, for example, analgesics. They tend to have less exposure misclassification bias and time-varying confounding if exposures are brief. Standard SCCS designs are bidirectional (using time both before and after the first exposure event), so they are more susceptible than CCOs to reverse-causality bias, including immortal-time bias. This is true also for sequence symmetry analysis, a simplified SCCS. Unidirectional CCOs use only time before the outcome, so they are less affected by reverse causality but susceptible to exposure-trend bias. Modifications of SCCS and CCO partially deal with these biases. The head-to-head comparison of multiple products helps to control residual biases. Conclusion The case-only analyses of intermittent users complement the cohort analyses of prolonged users because their different biases compensate for one another. Copyright © 2012 John Wiley & Sons, Ltd. key words-methods; safety monitoring; self-controlled designs; crossover Pharmacoepidemiologists who monitor the safety of medical products using healthcare administrative databases are increasingly interested to know when case-only designs can or cannot be used. To address this question, we (i) defined case-only designs in relation to each other; (ii) examined their main strength: self-controlled comparisons; (iii) discussed the major difference among the designs: directionality; (iv) described the range of medical products assessed with these designs in relation to their susceptibility to exposure misclassification; and (v) made recommendations to safety surveillance programs. DEFINITIONS AND ILLUSTRATIONSThe defining feature of case-only designs is that the analysis is restricted to cases, that is, people who experience at least one outcome event. Also in these designs, each individual serves as his or her own self-matched control, hence the term self-controlled.1-3 The term crossover arises when the analysis is restricted to people who supply both exposed and unexposed person-time and thus 'crossover' between two or more exposure levels. 4,5

The use of synthetic mesh to augment vaginal repair procedures for pelvic organ prolapse has increased in large part because of dissatisfaction with the success rates of traditional colporrhaphy. Its use, however, is controversial. Four randomized controlled studies comparing traditional colporrhaphy with vaginal repair using mesh augmentation had conflicting results. This unblinded, prospective, randomized controlled trial investigated whether mesh augmentation during vaginal repair would reduce the rate of recurrent prolapse at 12 months compared with traditional colporrhaphy. A total of 139 women with stage 2 or more prolapse who required both anterior and posterior compartment repair were randomized to mesh augmentation (mesh group, n ϭ 69) or colporrhaphy (no mesh group, n ϭ 70). Study subjects were enrolled between 2003 and 2005 at a tertiary teaching hospital. Prolapse was staged using the pelvic-organ-prolapse quantification (POP-Q) system. The primary study outcome was objective success of surgery defined as the absence of POP-Q stage 2 or more prolapse at 12 months following surgery. Questionnaires were used to assess secondary outcomes including symptoms, quality of life, and patient satisfaction.Of the 139 women, 63 of 69 (93.1%) in the mesh group and 61 of 70 (87.1%) in the no mesh group attended the 12-month follow-up. There was no significant difference at 12 months in objective success (POP-Q stage 0 or 1) between the mesh and no mesh groups (mesh: 81.0% ͓51/63͔ vs. no mesh: 65.6% ͓40/61͔; P ϭ 0.07). Although patients in both groups expressed a high level of satisfaction with the surgery and improved symptoms and parameters of quality of life compared to baseline, there was no statistically significant difference in these outcomes between the 2 groups (P ϭ ns). Postoperative complications in the mesh group included four cases (5.6%) of vaginal mesh exposure. At 12 months, de novo dyspareunia was reported in 27.8% (5/18) of the sexually active women without preoperative dyspareunia in the mesh group and in 41.7% (5/12) of those in the no mesh group. These differences were not significant (P ϭ 0.46).These findings show that anterior and posterior vaginal repair with mesh augmentation at 12 months after surgery does not result in significantly less recurrent prolapse than traditional colporrhaphy. GYNECOLOGY Volume 64, Number 12 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACTThe presence of myomas can impair fertility. To preserve fertility in women with myomas wanting to become pregnant, myomectomy can be performed with laparotomy, laparoscopy, or hysteroscopy and achieve pregnancy rates of up to 70%. Advantages of laparoscopic techniques compared with laparotomy include shorter hospital stay, more rapid recovery, and less intra-abdominal adhesions. In addition, the overall complication rate is lower. Precise dissection and suturing, however, is especially difficult with traditional laparoscopy for myomas with a deep intramural and/or another unfavorable localization that have a probable impact on fec...