STANDARD OPIATE PRESCRIBING IN PEDIATRIC AND ADOLESCENT GYNECOLOGIC SURGERY TO REDUCE OPIATE USE: BRIEF REPORT.

STUDY OBJECTIVE: The aim of this quality improvement (QI) project was to assess postoperative narcotic use after pediatric gynecologic surgeries and establish standard postoperative opioid dosing. Through standard dosing we hoped to decrease variability in postoperative opioid prescriptions and decrease excess opioid doses in the community. METHODS: This QI project was approved by the Children's Minnesota IRB. Counseling on postoperative pain management was provided pre- and post-operatively. At the two-week postoperative visit, patients were asked the number of opioid doses used and pain control satisfaction. Baseline data was collected for 6 months with surgeons prescribing the number of opioid doses based on their personal preference. After reviewing the prescribing practices and number of doses used, standard opioid doses were established, and data collection repeated. RESULTS: Complete data was recorded for 30 cases prior to implementation of standard doses and for 29 cases following implementation. Standardized opioid dosing resulted in 30% decrease in total opioid doses in circulation (252→176 doses; P=0.014) and 15% reduction in excess doses in circulation (162→137 doses). Forty-three percent of patients did not use any opioid doses. There was no significant difference P=0.8818) in patient pain control satisfaction rating. CONCLUSIONS: Standard opioid dose prescribing is feasible for common pediatric gynecologic surgeries without affecting patient pain control satisfaction. Opioid dose standardization may decrease opioid circulation within the community. Approximately 2 out of every 5 patients used zero opioid doses which suggests further reduction in the standard dose prescriptions is possible.

Nitrous Oxide Use for Intrauterine System Placement in Adolescents.

STUDY OBJECTIVE: To evaluate the impact of nitrous oxide on patient-reported pain for placement of intrauterine systems (IUSs) in adolescents STUDY DESIGN: : Prospective observational study SETTING: : IUS placement in an ambulatory clinic compared with placement with nitrous oxide in a hospital-based sedation unit PARTICIPANTS: : English-speaking adolescents aged 12 to 20 presenting to a pediatric and adolescent gynecologist with a medical indication for IUS placement MAIN OUTCOME MEASURES: : Patient-reported procedural pain measured on a visual analog scale 2 minutes post IUS insertion procedure. Secondary outcome measurement of likelihood of recommending an IUS to a peer. RESULTS: Seventy-four patients agreed to participate. Forty-five patients underwent IUS placement in the clinic. Controlling for age, history of dysmenorrhea, and body mass index, a significant time (change in reported pain scores pre- vs post IUS insertion) by treatment (nitrous oxide vs standard of care) interaction was observed for patient-reported pain (b = -29.32 mm, P < 0.01). Patients receiving nitrous oxide were more likely to recommend an intrauterine placement than patients who received the current standard of care for pain management (b = 0.47, P = 0.02) after controlling for age, baseline pain score, and dysmenorrhea history. CONCLUSION: Patient-reported pain was attenuated for patients who received nitrous oxide relative to those who received standard IUS placement. Patient-reported satisfaction was higher for patients who received nitrous oxide relative to those who received standard IUS placement.

Potential Telomere-Related Pharmacological Targets.

Telomeres function as protective caps at the terminal portion of chromosomes, containing non-coding nucleotide sequence repeats. As part of their protective function, telomeres preserve genomic integrity and minimize chromosomal exposure, thus limiting DNA damage responses. With continued mitotic divisions in normal cells, telomeres progressively shorten until they reach a threshold at a point where they activate senescence or cell death pathways. However, the presence of the enzyme telomerase can provide functional immortality to the cells that have reached or progressed past senescence. In senescent cells that amass several oncogenic mutations, cancer formation can occur due to genomic instability and the induction of telomerase activity. Telomerase has been found to be expressed in over 85% of human tumors and is labeled as a near-universal marker for cancer. Due to this feature being present in a majority of tumors but absent in most somatic cells, telomerase and telomeres have become promising targets for the development of new and effective anticancer therapeutics. In this review, we evaluate novel anticancer targets in development which aim to alter telomerase or telomere function. Additionally, we analyze the progress that has been made, including preclinical studies and clinical trials, with therapeutics directed at telomere-related targets. Furthermore, we review the potential telomere-related therapeutics that are used in combination therapy with more traditional cancer treatments. Throughout the review, topics related to medicinal chemistry are discussed, including drug bioavailability and delivery, chemical structure-activity relationships of select therapies, and the development of a unique telomere assay to analyze compounds affecting telomere elongation.

Oligonucleotides Targeting Telomeres and Telomerase in Cancer.

Telomeres and telomerase have become attractive targets for the development of anticancer therapeutics due to their involvement in cancer cell immortality. Currently, several therapeutics have been developed that directly target telomerase and telomeres, such as telomerase inhibitors and G-quadruplex stabilizing ligands. Telomere-specific oligonucleotides that reduce telomerase activity and disrupt telomere architecture are also in development as novel anticancer therapeutics. Specifically, GRN163L and T-oligos have demonstrated promising anticancer activity in multiple cancers types via induction of potent DNA damage responses. Currently, several miRNAs have been implicated in the regulation of telomerase activity and may prove to be valuable targets in the development of novel therapies by reducing expression of telomerase subunits. Targeting miRNAs that are known to increase expression of telomerase subunits may be another strategy to reduce carcinogenesis. This review aims to provide a comprehensive understanding of current oligonucleotide-based anticancer therapies that target telomeres and telomerase. These studies may help design novel therapeutic approaches to overcome the challenges of oligonucleotide therapy in a clinical setting.

Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance.

Lung cancer is treated with many conventional therapies, such as surgery, radiation, and chemotherapy. However, these therapies have multiple undesirable side effects. To bypass the side effects elicited by these conventional treatments, molecularly-targeted therapies are currently in use or under development. Current molecularly-targeted therapies effectively target specific biomarkers, which are commonly overexpressed in lung cancers and can cause increased tumorigenicity. Unfortunately, several molecularly-targeted therapies are associated with initial dramatic responses followed by acquired resistance due to spontaneous mutations or activation of signaling pathways. Acquired resistance to molecularly targeted therapies presents a major clinical challenge in the treatment of lung cancer. Therefore, to address this clinical challenge and to improve lung cancer patient prognosis, we need to understand the mechanism of acquired resistance to current therapies and develop additional novel therapies. This review concentrates on various lung cancer biomarkers, including EGFR, ALK, and BRAF, as well as their potential mechanisms of drug resistance.

Evaluation and Management of Adolescents with Abnormal Uterine Bleeding.

The International Federation of Gynecology and Obstetrics and the American Congress of Obstetricians and Gynecologists support the use of new terminology for abnormal uterine bleeding (AUB) to consistently categorize AUB by etiology. The term AUB can be further classified as AUB/heavy menstrual bleeding (HMB) (replacing the term "menorrhagia") or AUB/intermenstrual bleeding (replacing the term "metrorrhagia"). Although many cases of AUB in adolescent women are attributable to immaturity of the hypothalamic-pituitary-ovarian axis, underlying bleeding disorders should be considered in women with AUB/HMB. This article reviews the new terminology for AUB, discusses important relevant features of history and examination, presents the laboratory evaluation of HMB, and describes hormonal (oral contraceptive pills, progestin-only methods, long-acting reversible contraceptives including intrauterine systems), hematologic (tranexamic acid and desmopressin), and surgical management options for AUB/HMB.

Menstrual concerns and intrauterine contraception among adolescent bariatric surgery patients.

OBJECTIVE: Adolescent obesity has dramatically increased in recent decades, and along with that so have other medical comorbidities, such as hypertension, diabetes, hyperlipidemia, nonalcoholic steatohepatitis, polycystic ovary syndrome (PCOS), and pseudotumor cerebri. Obesity and related comorbidites may be contraindications to hormonal contraception, making contraception counseling of morbidly obese adolescents more challenging. Obese adolescent females seeking bariatric surgery need effective contraception in the postoperative period. This study is designed to determine the acceptance rate of the levonorgestrel-releasing intrauterine device (IUD) and describe common menstrual problems in obese adolescent bariatric surgery patients. METHODS: This is a historic cohort study of adolescent females who underwent bariatric surgery over a 2-year period at a tertiary referral center for pediatric obesity. Data were systematically abstracted. The percent of patients with menstrual problems and the acceptance rate for the levonorgestrel-releasing IUD were determined. RESULTS: Twenty-five adolescents met inclusion criteria. The mean age was 17.4 years (standard deviation [SD] 2.6), and the mean body mass index (BMI) was 51.4 (SD 6.3) kg/m(2). Eighty-four percent were white. Twenty-eight percent had menorrhagia, 32% had oligomenorrhea, 40% had dysmenorrhea, and 36% had PCOS. Ninety-two percent (23 of 25) underwent IUD placement. CONCLUSIONS: There was a high prevalence of menstrual problems among this sample of severely obese adolescent females. The majority accepted the IUD, indicating it is a viable option among this population.

Surgical correction of vaginal anomalies.

Summary of accurate diagnosis and surgical management of vaginal anomalies. Imperforate hymen, transverse septa, and distal vaginal agenesis present similarly with pain and hematocolpos. Likewise, imperforate hymen, transverse septa, distal vaginal agenesis, and Müllerian aplasia may appear similarly on examination. Imaging should be used to better differentiate the anomaly. Although surgical correction is the mainstay of hymenal anomalies, septa, obstructed hemivaginas, and distal vaginal agenesis, first-line therapy for Müllerian aplasia is progressive dilation. Many surgical techniques are also described but no consensus exists as to the best one. Clinicians should be aware of the appropriate evaluation, differential diagnosis, and management options available for vaginal anomalies.

Bariatric surgery and adolescent gynecology.

PURPOSE OF REVIEW: This review summarizes the impact of bariatric surgery on gynecologic complications in the context of the extremely obese adolescent and reviews contraceptive considerations before and after adolescent bariatric surgery. RECENT FINDINGS: Eighteen percent of children and adolescents have a body mass index greater than the 95th percentile, with 4% of adolescents being greater than the 99th percentile. Gynecologic morbidities identified in obese adolescents include anovulatory complications such as acute menorrhagia, polycystic ovary syndrome and endometrial hyperplasia, and cancer. When conventional dietary and behavioral therapy fail to result in weight loss, specific criteria have been identified to justify bariatric surgery in extremely obese adolescents. Bariatric surgery in adult women often results in resumption of ovulatory menses, resolution of clinical and laboratory evidence of hyperandrogenism, and return of fertility. Adolescents are at risk for unintended pregnancies, and there are special concerns regarding pregnancy in bariatric patients. Specific contraceptive methods have particular potential risks, benefits, and drawbacks for use in obese adolescents. SUMMARY: Clinicians who provide care for extremely obese adolescents must be aware of the potential for gynecologic morbidities including polycystic ovary syndrome, dysfunctional bleeding and endometrial hyperplasia, expected gynecologic and fertility outcomes of weight loss surgery for teens, as well as the implications on contraceptive options.