Catherine T. Witkop

Benefits and risks of oral diabetes agents compared with insulin in women with gestational diabetes: A systematic review

OBJECTIVE: Little is known about the comparative risks and benefits of medical treatments for gestational diabetes mellitus (GDM). We conducted a systematic review of randomized controlled trials and observational studies of maternal and neonatal outcomes in women with GDM treated with oral diabetes agents compared with all types of insulin. DATA SOURCES: We searched four electronic databases from inception through January 2007. Terms for GDM, insulins, and oral hypoglycemic agents were used in the search. Two investigators independently reviewed titles and abstracts, performed data abstraction on full articles, and assessed study quality. METHOD OF STUDY SELECTION: Articles were excluded if they had no comparison group or did not use a standard diagnosis of GDM (3-hour, 100-g oral glucose tolerance test or 2-hour, 75-g oral glucose tolerance test). Nine studies met our inclusion criteria, four randomized controlled trials (n=1,229 participants) and five observational studies (n=831 participants). Data were abstracted on study characteristics, gestational age at treatment, medication dosage, and length of follow-up. Outcomes included glycemic control, infant birth weight, neonatal hypoglycemia, and congenital anomalies. TABULATION, INTEGRATION, AND RESULTS: Two trials compared insulin to glyburide; one trial compared insulin, glyburide, and acarbose; and one trial compared insulin to metformin. No significant differences were found in maternal glycemic control or cesarean delivery rates between the insulin and glyburide groups. A meta-analysis showed similar infant birth weights between women treated with glyburide and women treated with insulin (mean difference –93 g) (95% confidence interval –191 to 5 g). There was a higher proportion of infants with neonatal hypoglycemia in the insulin group (8.1%) compared with the metformin group (3.3%) (P=.008). The rate of congenital malformations did not differ between pregnancies treated with insulin and those treated with oral agents. Observational studies were limited by selection bias and confounding. CONCLUSION: No substantial maternal or neonatal outcome differences were found with the use of glyburide or metformin compared with use of insulin in women with GDM.

Use of metformin in polycystic ovary syndrome: A meta-analysis

OBJECTIVE: To update the state of evidence on the efficacy of metformin, used either alone or in combination with clomiphene citrate in women with polycystic ovary syndrome, by examining three outcomes: ovulation, pregnancy, and live birth. Sources of heterogeneity among the published randomized controlled trials are systematically assessed. DATA SOURCES: An electronic literature search was performed using MEDLINE, EMBASE, SCOPUS, CENTRAL, Cochrane, and U.S. Food and Drug Administration databases, restricted to studies conducted on humans and published in English. METHODS OF STUDY SELECTION: Of the 406 potentially relevant articles identified, 17 met criteria for inclusion in the meta-analysis, rendering a total sample of 1,639 women. Study quality was examined in terms of randomization scheme, masking process, adequacy of allocation concealment, statistical power, and loss to follow-up; publication bias was also assessed. Meta-analytic procedures were used to compare metformin with placebo, and metformin plus clomiphene with clomiphene alone, for all study outcomes. Exploratory analyses were conducted to assess differences in treatment effects between clomiphene-resistant and nonresistant patients, obese and nonobese patients, and trials with long and short durations of follow-up. TABULATION, INTEGRATION, AND RESULTS: Metformin improved the odds of ovulation in women with polycystic ovary syndrome when compared with placebo (odds ratio [OR] 2.94; 95% confidence interval [CI] 1.43–6.02; number-needed-to-treat 4.0) and appears more effective for non–clomiphene-resistant women. Metformin and clomiphene increased the likelihood of ovulation (OR 4.39; 95% CI 1.94–9.96; number-needed-to-treat 3.7) and pregnancy (OR 2.67; 95% CI 1.45–4.94; number-needed-to-treat 4.6) when compared with clomiphene alone, especially in clomiphene-resistant and obese women with polycystic ovary syndrome. These treatment effects were greater for trials with shorter follow-up. CONCLUSION: Using all available evidence, this meta-analysis suggests that metformin increases the likelihood of ovulation and, in combination with clomiphene, increases the odds of both ovulation and pregnancy in women with polycystic ovary syndrome.

Novel influenza A (H1N1) outbreak at the U.S. Air Force Academy: epidemiology and viral shedding duration.

BACKGROUND The U.S. Air Force Academy is an undergraduate institution that educates and trains cadets for military service. Following the arrival of 1376 basic cadet trainees in June 2009, surveillance revealed an increase in cadets presenting with respiratory illness. Specimens from ill cadets tested positive for novel influenza A (H1N1 [nH1N1])-specific ribonucleic acid (RNA) by real-time reverse transcriptase-polymerase chain reaction. PURPOSE The outbreak epidemiology, control measures, and nH1N1 shedding duration are described. METHODS Case patients were identified through retrospective and prospective surveillance. Symptoms, signs, and illness duration were documented. Nasal-wash specimens were tested for nH1N1-specific RNA. Serial samples from a subset of 53 patients were assessed for presence of viable virus by viral culture. RESULTS A total of 134 confirmed and 33 suspected cases of nH1N1 infection were identified with onset date June 25-July 24, 2009. Median age of case patients was 18 years (range, 17-24 years). Fever, cough, and sore throat were the most commonly reported symptoms. The incidence rate among basic cadet trainees during the outbreak period was 11%. Twenty-nine percent (31/106) of samples from patients with temperature <100 degrees F and 19% (11/58) of samples from patients reporting no symptoms for > or = 24 hours contained viable nH1N1 virus. Of 29 samples obtained 7 days from illness onset, seven (24%) contained viable nH1N1 virus. CONCLUSIONS In the nH1N1 outbreak under study, the number of cases peaked 48 hours after a social event and rapidly declined thereafter. Almost one quarter of samples obtained 7 days from illness onset contained viable nH1N1 virus. These data may be useful for future investigations and in scenario planning.

Active Compared With Expectant Delivery Management in Women With Gestational Diabetes: A Systematic Review

OBJECTIVE: We conducted a systematic review to estimate benefits and harms of the choice of timing of induction or elective cesarean delivery based on estimated fetal weight or gestational age in women with gestational diabetes mellitus (GDM). DATA SOURCES: An electronic literature search was performed using MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, and The Cochrane Central Register of Controlled Trials from inception to January 2007. METHODS OF STUDY SELECTION: Two investigators independently reviewed titles and abstracts, assessed article quality, and abstracted data. Maternal outcomes included cesarean delivery and operative vaginal delivery. Neonatal outcomes included birth weight, macrosomia, large for gestational age, shoulder dystocia, birth trauma, neonatal intensive care admissions, and perinatal mortality. TABULATION, INTEGRATION, AND RESULTS: Five studies met our inclusion criteria: one randomized controlled trial (RCT) and four observational studies. The RCT (n=200) compared the effect of labor induction at term with expectant management. The proportion of newborns with birth weight greater than the 90th percentile was significantly greater in the expectant-management group (23% compared with 10% with active induction, P=.02); there were no significant differences in rates of cesarean delivery, shoulder dystocia, neonatal hypoglycemia, or perinatal deaths. The four observational studies suggest a potential reduction in macrosomia and shoulder dystocia with labor induction and cesarean delivery for estimated fetal weight indications, but there was insufficient evidence to assess other clinical outcomes. CONCLUSION: Active rather than expectant management of labor at term for women with GDM may reduce rates of macrosomia and related complications. Further RCTs and observational studies with a broader range of outcomes are needed for sufficient evidence to inform clinical practice.

Natural History of Fetal Position During Pregnancy and Risk of Nonvertex Delivery

OBJECTIVE: To examine the natural history of fetal position throughout pregnancy and the likelihood for nonvertex delivery. METHODS: We examined fetal positions at 15–22 weeks, at 31–35 weeks, and at delivery using data from the Routine Antenatal Diagnostic Imaging with Ultrasound trial. Characteristics of women with nonvertex and vertex presentation at delivery were compared. Multivariable logistic regression analysis was performed to determine risk factors for nonvertex presentation at delivery, and odds ratios were calculated for those risk factors found to be statistically significantly associated with nonvertex presentation. RESULTS: Data for 7,045 women who underwent routine prenatal ultrasound examinations were analyzed. We found no association between nonvertex presentation at 15–22 and at 31–35 weeks of gestation. A nonvertex fetus at 35 weeks had a 45% chance of spontaneous version by delivery. Multivariable logistic regression analysis found that multiparous women had half of the risk of nonvertex presentation as nulliparous women. Smoking during pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.10–1.96), low volume of amniotic fluid at 31–35 weeks (OR 3.74, 95% CI 1.85–7.53), and fundal position of the placenta at late ultrasound examination (OR 1.85, 95% CI 1.23–2.78) were all associated with significant increases in the risk of nonvertex position at delivery. CONCLUSION: Spontaneous version of a nonvertex fetus at 35 weeks of gestation is still likely. LEVEL OF EVIDENCE: II

Understanding the Spectrum of the Female Athlete Triad

A 21-year-old woman, an intercollegiate cross-country runner, presented for a routine well-woman examination and mentioned recent onset of left heel pain that was making it difficult to train. She denied any chronic medical problems or surgeries, but stated she had been treated 1 year previously for a right tibial stress fracture. At that time, she was exercising 6 to 7 days a week for about 4 hours per day (running about 55 mi/wk) and was diagnosed by her primary care provider with a “stress reaction” based on magnetic resonance imaging. She was started on a oncedaily supplement of calcium 500 mg as well as oral contraceptive pills (ethinyl estradiol/drospirenone) and was told to reduce training and refrain from high-impact exercise. When she returned 2 months later, she denied any ongoing pain, reported monthly cycles on the oral contraceptive pills, and was cleared to return to running. The patient stated that the pain in her left heel began 1 week before presentation. She recently had increased her weekly mileage to 65 miles per week without any change in her strict vegetarian diet (about 1,800 kcal/d). She reported being content with her weight and body image and denied any binging or purging behavior. Aside from school and competitive running, she denied any new stressors. She reported menarche at age 17, followed by approximately one to two periods per year, usually when off season, but stated that she had had “regular periods” since beginning oral contraceptives 1 year previously. She was not sexually active. On physical examination, the patient was 5 feet 6 inches tall and weighed 114 pounds, with a body mass index of 18.4. Her physical examination was otherwise unremarkable. A dual energy X-ray absorptiometry scan was obtained and revealed a Z-score of -1.0 in the left femoral neck (bone mineral density [BMD] 0.873 g/cm) and -2.8 in the spine (BMD 0.736 g/cm). Magnetic resonance imaging confirmed a suspected stress fracture of the left heel (calcaneal tuberosity). The patient was counseled extensively about energy availability and risks to her future bone health. After an explanation of the relationship between energy availability and her menstrual cycles, she agreed to discontinue oral contraceptives. Her calcium intake was increased to 1,000 mg/d, and she was started on vitamin D (800 international units/d). She was told to stop training; referred to a dietician for further counseling, including increasing her energy intake and weight; and instructed to return in 2 weeks for follow-up.

Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper

OBJECTIVE To assess current practice, advise minimum standards, and identify educational gaps relevant to genetic screening, counseling, and testing of women affected by gynecologic cancers. METHODS The Society of Gynecologic Oncology (SGO) organized a multidisciplinary summit that included representatives from the American College of Obstetricians and Gynecologists (ACOG), the American Society Clinical Oncology (ASCO), the National Society of Genetic Counselors (NSGC), and patient advocacy groups, BrightPink and Facing our Risk of Cancer Empowered (FORCE). Three subject areas were discussed: care delivery models for genetic testing, barriers to genetic testing, and educational opportunities for providers of genetic testing. RESULTS The group endorsed current SGO, National Comprehensive Cancer Network (NCCN), and NSGC genetic testing guidelines for women affected with ovarian, tubal, peritoneal cancers, or DNA mismatch repair deficient endometrial cancer. Three main areas of unmet need were identified: timely and universal genetic testing for women with ovarian, fallopian tube, and peritoneal cancers; education regarding minimum standards for genetic counseling and testing; and barriers to implementation of testing of both affected individuals as well as cascade testing of family members. Consensus building among all stakeholders resulted in an action plan to address gaps in education of gynecologic oncology providers and delivery of cancer genetics care.

Screening for Sickle-Cell Trait at Accession to the United States Military

Condition Definition SCT is a heterozygotic carrier state in which an individual has one copy of the normal HbA gene and one copy of the HbS variant. Commercial tests for SCT have been available since the early 1970s. The sickle solubility test qualitatively detects the presence of HbS by precipitating sickle hemoglobin in the presence of an oxygen depleting reagent. With a sensitivity approaching 99% and a specificity of 100%, sickle solubility provides an accurate screening method. The hemoglobin electrophoresis test is a confirmatory test that quantifies the percentage of HbS and is therefore able to distinguish among the HbS disorders, such as SCT or sicklecell disease. According to the 59th Clinical Lab Flight at Joint Base San Antonio-Lackland, Texas (oral communication, November 2013), the U.S. Air Force (USAF) spends

Varicella seroepidemiology in United States air force recruits: A retrospective cohort study comparing immunogenicity of varicella vaccination and natural infection

4.86 on the sickle solubility test and

Disparities in receipt of a laparoscopic operation for ectopic pregnancy among TRICARE beneficiaries

9.41 on the hemoglobin electrophoresis test.