Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events. (Funded by Merck Sharp & Dohme; TECOS ClinicalTrials.gov number, NCT00790205.).

The pharmacokinetics and bioavailability of cyclobenzaprine, a widely used muscle relaxant, were investigated in four clinical studies, and the effects of age, gender, and hepatic insufficiency were characterized. Cyclobenzaprine plasma clearance was 689 ml/min, and the bioavailability of a 5 mg oral dose was 0.55. Following oral doses of 2.5 to 10 mg tid in healthy young subjects, cyclobenzaprine pharmacokinetics were linear, and plasma concentrations generally increased proportional to dose. There was about a fourfold accumulation of the drug in plasma on multiple dosing, corresponding to an effective half-life of 18 hours. Steady-state plasma concentrations of cyclobenzaprine in elderly subjects were twice as high as in young subjects following oral doses of 5 mg tid. Steady-state plasma concentration also appeared to be up to twofold higher in subjects with mild hepatic insufficiency compared to healthy controls. The magnitude of any difference in steady-state plasma concentration between males and females appears to be small relative to intersubject variability. A reduction in dose or dosing frequency should be considered in the elderly and in patients with liver disease.

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Although only 4.5% to 16% of ovarian cysts in children are malignant, oophorectomy is common in such patients. Conservative expectant management and ovarian sparing surgery would avoid bilateral oophorectomies in children with ovarian cysts at low risk of malignancy. Pediatric or general surgeons who have limited expertise with pediatric gynecology often manage these children because of limited availability of pediatric and adolescent gynecologists with the special skills needed.The objective of this retrospective case-note study was to investigate the nature and surgical management of ovarian cysts in children at a large children's hospital to determine whether current management practices could be improved. Between 1991 and 2007, 155 cases identified through use of clinical coding of surgical cases and pathology databases were analyzed by use of Snap 9.Sixty-two ovarian cysts were found in children under 9 years of age who were prepubertal. There were 58 neoplastic cysts, but 36 (62%) were benign teratomas. Ten of the cysts were malignant. Preoperative diagnostic investigation was preformed in a minority of the patients: Of the 155 children, only 16 (10%) were investigated for tumor markers; 61 (39%) had an ultrasound scan; and 16 (10%) had a computed tomography or magnetic resonance imaging scan. An oophorectomy was performed in 90 (58%) of the children and an ovarian cystectomy was performed in 40 (26%). The ovary was removed in all cases with malignant cysts, and in 75 cases with benign or normal pathology (including 5 benign epithelial, 9 functional and 4 paraovarian cysts; 5 cases with normal ovarian tissue; 30 oophorectomies for benign teratomas, 21 for torsion and 1 for hemorrhage). Referral to a pediatric gynecologist occurred for only 24 (15.5%) of the patients following surgery for an ovarian cyst. This number excluded the 10 girls who were still in pain. None of the referrals were before surgery.These findings show that a large number of young girls with benign cysts who are at low risk of malignancy have cystectomy or oophorectomy when a conservative expectant management approach or ovarian-sparing surgery could have been justified. To prevent this practice, the investigators recommend greater use of preoperative diagnostic investigations including tumor markers and imaging, and the training of more gynecologists with the special skills in pediatric and adolescent gynecology needed to manage these patients. EDITORIAL COMMENT(In this retrospective analysis of ovarian cysts in children and adolescents from England, a surprisingly large number of patients were man-aged by oophorectomy and open laparotomy. Cases in this review (and certainly in most reports) were identified by searching the pathol- GYNECOLOGY Volume 65, Number 3 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACTBecause hysterectomy, the standard treatment option for women of reproductive age with menorrhagia, is associated with serious complications and requires a relatively long-recovery period, the levonorgestrel-releasing intrauterine sys...

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