Wanda K Nicholson

Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations.

BACKGROUND Given the increase in medications for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices. PURPOSE To summarize the benefits and harms of metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 receptor agonists, as monotherapy and in combination, to treat adults with type 2 diabetes. DATA SOURCES MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through April 2010 for English-language observational studies and trials. The MEDLINE search was updated to December 2010 for long-term clinical outcomes. STUDY SELECTION Two reviewers independently screened reports and identified 140 trials and 26 observational studies of head-to-head comparisons of monotherapy or combination therapy that reported intermediate or long-term clinical outcomes or harms. DATA EXTRACTION Two reviewers following standardized protocols serially extracted data, assessed applicability, and independently evaluated study quality. DATA SYNTHESIS Evidence on long-term clinical outcomes (all-cause mortality, cardiovascular disease, nephropathy, and neuropathy) was of low strength or insufficient. Most medications decreased the hemoglobin A(1c) level by about 1 percentage point and most 2-drug combinations produced similar reductions. Metformin was more efficacious than the DPP-4 inhibitors, and compared with thiazolidinediones or sulfonylureas, the mean differences in body weight were about -2.5 kg. Metformin decreased low-density lipoprotein cholesterol levels compared with pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a 4-fold higher risk for mild or moderate hypoglycemia than metformin alone and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones increased risk for congestive heart failure compared with sulfonylureas and increased risk for bone fractures compared with metformin. Diarrhea occurred more often with metformin than with thiazolidinediones. LIMITATIONS Only English-language publications were reviewed. Some studies may have selectively reported outcomes. Many studies were small, were of short duration, and had limited ability to assess clinically important harms and benefits. CONCLUSION Evidence supports metformin as a first-line agent to treat type 2 diabetes. Most 2-drug combinations similarly reduce hemoglobin A(1c) levels, but some increased risk for hypoglycemia and other adverse events. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

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.

Risk Factors for Type 2 Diabetes Among Women with Gestational Diabetes: A Systematic Review

We conducted a systematic review of studies examining risk factors for the development of type 2 diabetes among women with previous gestational diabetes. Our search strategy yielded 14 articles that evaluated 9 categories of risk factors of type 2 diabetes in women with gestational diabetes: anthropometry, pregnancy-related factors, postpartum factors, parity, family history of type 2 diabetes, maternal lifestyle factors, sociodemographics, oral contraceptive use, and physiologic factors. The studies provided evidence that the risk of type 2 diabetes was significantly higher in women having increased anthropometric characteristics with relative measures of association ranging from 0.8 to 8.7 and women who used insulin during pregnancy with relative measures of association ranging between 2.8 and 4.7. A later gestational age at diagnosis of gestational diabetes, >24 weeks gestation on average, was associated with a reduction in risk of development of type 2 diabetes with relative measures of association ranging between 0.35 and 0.99. We concluded that there is substantial evidence for 3 risk factors associated with the risk of type 2 diabetes in women having gestational diabetes.

Depressive symptoms and health-related quality of life in early pregnancy.

OBJECTIVE: Depressive symptoms can be associated with lower health-related quality of life in late pregnancy. Few studies have quantified the effect of depressive symptoms in early pregnancy or among a racially and economically diverse group. Our goal was to estimate the independent association of depressive symptoms with health-related quality of life among a diverse group of women in early pregnancy. METHODS: We conducted a cross-sectional study of 175 pregnant women receiving prenatal care in a community and university-based setting. We related the presence of depressive symptoms, defined as a Center for Epidemiologic Studies Depression Scale score of 16 or more to health-related quality of life scores from the 8 Medical Outcomes Study Short Form domains: Physical Functioning, Role-Physical, Bodily Pain, Vitality, General Health, Social Functioning, Role-Emotional, and Mental Health. Quantile regression was used to measure the independent association of depressive symptoms with each of the 8 domains. RESULTS: The study sample was 49% African American, 38% white, and 11% Asian. Mean (± standard deviation) gestational age was 14 ± 6 weeks.The prevalence of depressive symptoms was 15%. Women with depressive symptoms had significantly lower health-related quality of life scores in all domains except Physical Functioning. After adjustment for sociodemographic, clinical, and social support factors, depressive symptoms were associated with health-related quality of life scores that were 30 points lower in Role-Physical, 19 points lower in Bodily Pain, 10 points lower in General Health, and 56 points lower in Role-Emotional. CONCLUSION: Women in early pregnancy with depressive symptoms have poor health-related quality of life. Early identification and management of depressive symptoms in pregnant women may improve their sense of well-being. LEVEL OF EVIDENCE: II-2

Barriers to and Facilitators of Postpartum Follow-Up Care in Women with Recent Gestational Diabetes Mellitus: A Qualitative Study

OBJECTIVES Women with a history of gestational diabetes mellitus (GDM) have an increased risk of developing type 2 diabetes (T2DM) but often do not return for follow-up care. We explored barriers to and facilitators of postpartum follow-up care in women with recent GDM. METHODS We conducted 22 semistructured interviews, 13 in person and 9 by telephone, that were audiotaped and transcribed. Two investigators independently coded transcripts. We identified categories of themes and subthemes. Atlas.ti qualitative software (Berlin, Germany) was used to assist data analysis and management. RESULTS Mean age was 31.5 years (standard deviation) [SD] 4.5), 63% were nonwhite, mean body mass index (BMI) was 25.9 kg/m(2) (SD 6.2), and 82% attended a postpartum visit. We identified four general themes that illustrated barriers and six that illustrated facilitators to postpartum follow-up care. Feelings of emotional stress due to adjusting to a new baby and the fear of receiving a diabetes diagnosis at the visit were identified as key barriers; child care availability and desire for a checkup were among the key facilitators to care. CONCLUSIONS Women with recent GDM report multiple barriers and facilitators of postpartum follow-up care. Our results will inform the development of interventions to improve care for these women to reduce subsequent diabetes risk.

Longitudinal Study of Depressive Symptoms and Health-Related Quality of Life During Pregnancy and After Delivery: The Health Status in Pregnancy (HIP) Study

Objective Depressive symptoms are known to affect functioning in early pregnancy. We estimated the effect of a change in depressive symptoms status on health-related quality of life (HRQoL) throughout pregnancy and after delivery. Methods Longitudinal study of 200 women. The independent variable was depressive symptoms, defined as a Center for Epidemiologic Studies Depression (CES-D) score of ≥16. The dependent variable was HRQoL from 8 domains of the Medical Outcomes Study (SF-36) Short Form. Women were categorized based on the change in CES-D score: (1) never depressed, (2) became well, (3) became depressed and (4) always depressed. A random effects model was used to (1) estimate the effect of a change in depressive symptomatology from the first to the second trimester on HRQOL in the second trimester and (2) estimate the change in depressive symptomatology from the second to the third trimester on HRQoL in the third trimester and after delivery, adjusting for covariates. Intra-individual correlations were accounted for using generalized estimating equations (GEE). Results The proportion of women with depressive symptoms was 15%, 14%, and 30% in the first, second and third trimesters, respectively, and 9% after delivery. Women who became depressed had scores in the social domains that were 10–23 points and 19–31 points lower in the second and third trimesters, respectively, compared to women with no depressive symptoms. Women who became well had scores that were 3–31 points lower, compared to women with no depressive symptoms. Conclusions Alterations in depressive symptomatology have a substantial effect on functioning during pregnancy and after delivery.

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.

The impact of uterine leiomyomas: A national survey of affected women

OBJECTIVE We sought to characterize the impact of uterine leiomyomas (fibroids) in a racially diverse sample of women in the United States. STUDY DESIGN A total of 968 women (573 white, 268 African American, 127 other races) aged 29-59 years with self-reported symptomatic uterine leiomyomas participated in a national survey. We assessed diagnosis, information seeking, attitudes about fertility, impact on work, and treatment preferences. Frequencies and percentages were summarized. The χ(2) test was used to compare age groups. RESULTS Women waited an average of 3.6 years before seeking treatment for leiomyomas, and 41% saw ≥2 health care providers for diagnosis. Almost a third of employed respondents (28%) reported missing work due to leiomyoma symptoms, and 24% believed that their symptoms prevented them from reaching their career potential. Women expressed desire for treatments that do not involve invasive surgery (79%), preserve the uterus (51%), and preserve fertility (43% of women aged <40 years). CONCLUSION Uterine leiomyomas cause significant morbidity. When considering treatment, women are most concerned about surgical options, especially women aged <40 years who want to preserve fertility.

The burden of uterine fibroids for African-American women: results of a national survey.

BACKGROUND Uterine fibroids have a disproportionate impact on African-American women. There are, however, no data to compare racial differences in symptoms, quality of life, effect on employment, and information-seeking behavior for this disease. METHODS An online survey was conducted by Harris Interactive between December 1, 2011 and January 16, 2012. Participants were U.S. women aged 29-59 with symptomatic uterine fibroids. African-American women were oversampled to allow statistical comparison of this high-risk group. Bivariate comparison of continuous and categorical measures was based on the t-test and the Chi-squared test, respectively. Multivariable adjustment of risk ratios was based on log binomial regression. RESULTS The survey was completed by 268 African-American and 573 white women. There were no differences between groups in education, employment status, or overall health status. African-American women were significantly more likely to have severe or very severe symptoms, including heavy or prolonged menses (RR=1.51, 95% CI 1.05-2.18) and anemia (RR=2.73, 95% CI 1.47-5.09). They also more often reported that fibroids interfered with physical activities (RR=1.67, 95% CI 1.20-2.32) and relationships (RR=2.27, 95% CI 1.23-4.22) and were more likely to miss days from work (RR=1.77, 95% CI 1.20-2.61). African-American women were more likely to consult friends and family (36 vs. 22%, P=0.004) and health brochures (32 vs. 18%, P<0.001) for health information. Concerns for future fertility (RR=2.65, 95% CI 1.93-3.63) and pregnancy (RR=2.89, 95% CI 2.11-3.97) following fibroid treatments were key concerns for black women. CONCLUSIONS African-American women have more severe symptoms, unique concerns, and different information-seeking behavior for fibroids.

Pelvic magnetic resonance imaging in the evaluation of uterine torsion

Background Uterine torsion is defined as the rotation of more than 45° around the long axis of the uterus. An uncommon but potentially fatal event, uterine torsion is rarely diagnosed until the time of surgery. With magnetic resonance imaging (MRI), however, an accurate diagnosis of uterine torsion may now be made preoperatively. Case We describe a patient with uterine torsion in whom the correct diagnosis was made prenatally with the use of MRI, by the demonstration of an X-shaped configuration of the upper vagina. Conclusion Distinctive features suggestive of uterine torsion were demonstrated by MRI and enabled an accurate preoperative diagnosis. To our knowledge, this is the first reported case of uterine torsion diagnosed on MRI.