Comparative effectiveness trial of metformin versus insulin for the treatment of gestational diabetes in the USA: clinical trial protocol for the multicentre DECIDE study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. Because metformin crosses the placenta, long-term safety data, in particular, the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remain to be characterised, including barriers to and facilitators of metformin versus insulin use. METHODS AND ANALYSIS: In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org. ETHICS AND DISSEMINATION: The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT06445946.

Neonatal Hypoglycemia following Late Preterm Antenatal Corticosteroid Administration in Individuals with Diabetes in Pregnancy.

OBJECTIVE: Antenatal corticosteroid (ACS) administration is standard practice for pregnant individuals delivering in the late preterm period, though no guidelines are in place for those with diabetes. This study aims to characterize the prevalence of neonatal hypoglycemia after ACS administration in pregnant individuals with diabetes delivering in the late preterm period. STUDY DESIGN: This is a retrospective, single-center, case-control study of individuals with diabetes who delivered between 340/7 and 366/7 weeks' gestation at a large academic medical center from 2016 to 2021. A total of 169 individuals were included in the analysis; 87 received corticosteroids and 82 did not. The proportion of neonates with hypoglycemia, neonatal intensive care unit (NICU) admission, respiratory distress syndrome, and hyperbilirubinemia were compared between parents who received ACSs versus those who did not. RESULTS: The prevalence of neonatal hypoglycemia (40.2 vs. 23.2%, p = 0.027), requiring treatment (40.3 vs. 22.4%, p = 0.041), and hyperbilirubinemia (35.6 vs 18.5%, p = 0.018) was greater for neonates born to individuals with diabetes who received late preterm ACSs compared with those who did not. There was no difference in NICU admission and respiratory distress between the groups. These results remained unchanged after controlling for confounders including gestational age at delivery and birth weight. CONCLUSION: This study demonstrates that late preterm corticosteroid administration to pregnant individuals with diabetes increases the risk for neonatal hypoglycemia without changing the rates of respiratory morbidity. KEY POINTS: · Late preterm ACS in diabetic patients resulted in higher rates of neonatal hypoglycemia.. · There are no differences in rates of respiratory distress syndrome and transient tachypnea of the newborn between the ACS group and control group.. · There was no noted difference in rate of NICU admission and length of stay between the two groups..

Telehealth for the Management of Diabetes in Pregnancy.

PURPOSE OF REVIEW: Telehealth initiatives are becoming ubiquitous in clinical practice and can be a useful tool in the management of diabetes in pregnancy. The purpose of this review is to summarize new techniques in telemedicine delivery and offer details on how to leverage telehealth in delivering care to pregnant women with diabetes. RECENT FINDINGS: Using mobile phone technology to collect glucose values in women with gestational diabetes has been found to be beneficial by increasing the amount of glucose data available for interpretation. Remote patient monitoring in non-pregnant people with type 2 diabetes has shown a modest improvement in glucose control. In pregnant women with diabetes, the use of remote patient monitoring does not appear to improve outcomes but can decrease in-office visits and lower healthcare costs. However, telehealth may not be the only solution to helping patients with diabetes in pregnancy who have difficulty engaging in their care. Telehealth affords improvements in convenience, efficiency, and frequency of communication with healthcare professionals, and the amount of data available to patients and providers alike, yielding the potential for better outcomes when telehealth modalities are adopted.

Conversion and optimization of telehealth in obstetric care during the COVID-19 pandemic.

When New York City became the international epicenter of the COVID-19 pandemic, telehealth at Columbia University Irving Medical Center was expanded in the inpatient and outpatient settings. The goals of telehealth during the pandemic were to maintain patient access to care while reducing the risk for COVID-19 exposure for patients and staff. Recommendations are made on how telehealth can be implemented and utilized to accomplish these goals. In the outpatient setting, virtual prenatal care visits and consultations can replace most in-person visits. When visitor restrictions are in effect telehealth can be used to engage support persons in the delivery room. Telehealth innovations can be leveraged to greatly improve care for COVID-19 mothers and their infants during the COVID-19 pandemic and beyond.

A new paradigm for the role of smooth muscle cells in the human cervix.

BACKGROUND: Premature cervical remodeling resulting in spontaneous preterm birth may begin with premature failure or relaxation at the internal os (termed "funneling"). To date, we do not understand why the internal os fails or why funneling occurs in some cases of premature cervical remodeling. Although the human cervix is thought to be mostly collagen with minimal cellular content, cervical smooth muscle cells are present in the cervix and can cause cervical tissue contractility. OBJECTIVE: To understand why the internal os relaxes or why funneling occurs in some cases of premature cervical remodeling, we sought to evaluate cervical smooth muscle cell content and distribution throughout human cervix and correlate if cervical smooth muscle organization influences regional cervical tissue contractility. STUDY DESIGN: Using institutional review board-approved protocols, nonpregnant women <50 years old undergoing hysterectomy for benign indications were consented. Cervical tissue from the internal and external os were immunostained for smooth muscle cell markers (α-smooth muscle actin, smooth muscle protein 22 calponin) and contraction-associated proteins (connexin 43, cyclooxygenase-2, oxytocin receptor). To evaluate cervical smooth muscle cell morphology throughout the entire cervix, whole cervical slices were obtained from the internal os, midcervix, and external os and immunostained with smooth muscle actin. To correlate tissue structure with function, whole slices from the internal and external os were stimulated to contract with 1 µmol/L of oxytocin in organ baths. In separate samples, we tested if the cervix responds to a common tocolytic, nifedipine. Cervical slices from the internal os were treated with oxytocin alone or oxytocin + increasing doses of nifedipine to generate a dose response and half maximal inhibitory concentration. Student t test was used where appropriate. RESULTS: Cervical tissue was collected from 41 women. Immunohistochemistry showed cervical smooth muscle cells at the internal and external os expressed mature smooth muscle cell markers and contraction-associated proteins. The cervix exhibited a gradient of cervical smooth muscle cells. The area of the internal os contained 50-60% cervical smooth muscle cells that were circumferentially organized in the periphery of the stroma, which may resemble a sphincter-like pattern. The external os contained approximately 10% cervical smooth muscle cells that were randomly scattered in the tissue. In organ bath studies, oxytocin stimulated the internal os to contract with more than double the force of the external os (1341 ± 693 vs 523 ± 536 integrated grams × seconds, respectively, P = .009). Nifedipine significantly decreased cervical tissue muscle force compared to timed vehicle control (oxytocin alone) at doses of 10(-5) mol/L (vehicle 47% ± 15% vs oxytocin + nifedipine 24% ± 16%, P = .007), 10(-4) mol/L (vehicle 46% ± 16% vs oxytocin + nifedipine -4% ± 20%, P = .003), and 10(-3) mol/L (vehicle 42% ± 14% vs oxytocin + nifedipine -15% ± 18%, P = .0006). The half maximal inhibitory concentration for nifedipine was 1.35 × 10(-5) mol/L. CONCLUSION: Our findings suggest a new paradigm for cervical tissue morphology-one that includes the possibility of a specialized sphincter at the internal os. This new paradigm introduces novel avenues to further investigate potential mechanisms of normal and premature cervical remodeling.

A systematic evaluation of collagen cross-links in the human cervix.

OBJECTIVE: The mechanical strength of the cervix relies on the cross-linking of the tissue's collagen network. Clinically, the internal os is functionally distinct from the external os. We sought to detect specific collagen cross-links in human cervical tissue and determine whether cross-link profiles were similar at the internal and external os. STUDY DESIGN: Transverse slices of cervical tissue were obtained at the internal and external os from 13 nonpregnant, premenopausal women undergoing a benign hysterectomy. To understand how cross-links were distributed throughout the entire cervix and at the internal and external os, biopsies were obtained from 3 circumferential zones in 4 quadrants from each slice. Biopsies were pulverized, lyophilized, reduced with sodium borohydride, hydrolyzed with hydrochloric acid, and reconstituted in heptafluorobutyric acid buffer. Hydroxyproline was measured by ultraperformance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), converted to total collagen, and normalized by dry weight. Collagen cross-links pyridinoline (PYD), deoxypyridinoline (DPD), dihydroxylysinonorleucine (DHLNL), and the nonenzymatic advanced glycation end product pentosidine (PEN) were measured by UPLC-ESI-MS/MS and reported as cross-link density ratio (cross-link/total collagen). Generalized estimated equation analysis was used to compare results between the internal and external os and to compare quadrants and zones within slices from the internal and external os to determine if cross-link profiles were similar. RESULTS: A total of 592 samples from 13 patients were analyzed. Collagen cross-links are detectable in the human cervix by UPLC-ESI-MS/MS. When comparing all samples from the internal and external os, similar levels of collagen content, PYD, DHLNL, and DPD were found, but PEN density was higher at the external os (0.005 vs 0.004, P = .001). When comparing all internal os samples, significant heterogeneity was found in collagen content and cross-link densities across zones and quadrants. The external os exhibited heterogeneity only across zones. CONCLUSION: Collagen cross-links (PYD, DPD, DHLNL, and PEN) are detectable by UPLC-ESI-MS/MS in the human cervix. The internal os exhibits significant collagen cross-link heterogeneity compared with the external os. Further studies are needed to evaluate how collagen cross-link heterogeneity correlates to the mechanical strength and function of the human cervix.

A tortuous proximal urethra in urorectal septum malformation sequence?

We observed a newborn boy with urorectal septum malformation sequence. Anomalies of the genitalia and rectum were present. He expired on the first day of life, due to severe lung hypoplasia. Autopsy showed a colon that ended in a blind sac, an enlarged bladder with no grossly visible urethra, and dysplastic kidneys. A cone-shaped tissue at the usual site of the bladder outlet contained tortuous and slit-like lumina, suggesting an undeveloped proximal urethra. The urethral structure was lined by transitional epithelium with squamous metaplasia. Many small buds-lined with columnar epithelium-branched from the urethral structure. These ductal buds lined with columnar epithelium stained for prostatic acid phosphatase. Basal cells surrounding the ductal buds stained for p63 and high molecular weight cytokeratin-supporting an interpretation that the buds were early prostatic ducts with normal histology. To our knowledge, these are the first histological images of an undeveloped, obstructed urethra associated with the urorectal septum malformation sequence.

Cervilenz assessment of cervical length compared to fetal fibronectin in the prediction of preterm delivery in women with threatened preterm labor.

OBJECTIVE: To determine whether cervical length (CL) measured by the Cervilenz™ measuring device is an effective screening tool for the prediction of preterm delivery (PTD) compared to fetal fibronectin (fFN). METHODS: We evaluated fFN and CL among women who enrolled into a randomized control trial (RCT) comparing management algorithms for threatened preterm labor between 24 and 34 weeks' gestation. In all subjects, fFN was collected, with CL determined in blinded fashion. The sensitivity, specificity, and positive and negative predictive values (NPV) for fFN or Cervilenz in prediction of PTD within 7 days or prior to 37 weeks were determined. RESULTS: Fifty-two subjects were evaluated. CL <30 mm correlated with PTD <7 days (r = 0.31, p = 0.04) and fFN positivity (r = 0.43, p = 0.006). CL <30 mm and fFN had excellent NPV for PTD <7 days (97.1 vs. 97.3%), and the area under the receiver operator characteristic curves were similar for prediction of PTD <7 days (76.6 vs. 75.2%, p = 0.71) or <37 weeks (56.7 vs. 55.2%, p = 0.71). CONCLUSIONS: Measurement of CL with Cervilenz appears to be equivalent to fFN in screening symptomatic women for PTD within 7 days or prior to 37 weeks. Given cost and turnaround time with fFN testing, Cervilenz represents a promising new tool for real time, clinically useful results in the management of women with threatened preterm labor.

Compliance differences between patients with breast cancer in university and county hospitals.

PURPOSE: Compliance with recommended breast cancer treatments outside the context of a clinical trial differs from that in study populations. The purpose of this study was to examine differences in compliance of breast cancer treatments. PATIENTS AND METHODS: We conducted a retrospective review of 529 patients treated at 2 teaching hospitals in the same city from 2003 to 2006. Compliance with adjuvant therapy recommendations and choice of breast-conserving operations were compared between a university hospital (UH) and a county hospital (CH). RESULTS: The 2 populations demonstrated similar rates of breast conservation (72% vs. 69%). Although use of radiation therapy at the CH was acceptable (82%), patients at the UH were more likely to undergo radiation therapy (95%). The use of hormone therapy was similar at the UH and the CH (> 93%). Patients were more likely to follow physician recommendations for adjuvant chemotherapy at the UH (89%) compared with the CH (70%; P = .0005). Univariate analysis revealed that patient age, tumor size, stage, grade, and estrogen receptor status were all significant predictors of patient compliance with chemotherapy. Preoperative chemotherapy was a strong predictor of patient compliance with chemotherapy (P < .0001). In multivariate analysis, all of the factors predictive of patient compliance in univariate analysis remained significant except tumor grade. CONCLUSION: Preoperative chemotherapy appeared to increase compliance compared with adjuvant chemotherapy in the CH population. Compared with national standards, breast-conserving operations and radiation therapy compliance can be accomplished in an acceptable percentage of underinsured patients.

Race and ethnicity and breast cancer outcomes in an underinsured population.

BACKGROUND: The disparity in breast cancer mortality between African American women and non-Hispanic white women has been the subject of increased scrutiny. Few studies have addressed these differences in the setting of equal access to health care. We compared the breast cancer outcomes of underinsured African American and non-Hispanic white patients who were treated at a single institution. METHODS: We conducted a retrospective review of medical records for breast cancer patients who were treated at Wishard Memorial Hospital from January 1, 1997, to February 28, 2006. A total of 574 patients (259 non-Hispanic whites and 315 African Americans) were evaluated. A Cox proportional hazards regression analysis for competing risks was performed. All statistical tests were two-sided. RESULTS: Sociodemographic characteristics were similar in the two groups, and both racial groups were equally unlikely to have undergone screening mammography during the 2 years before diagnosis. Most (84%) of the patients were underinsured. The median time from diagnosis to operation, receipt of adequate surgery, and use of all types of adjuvant therapy were similar in the two groups. Median follow-up was 80.3 months for non-Hispanic whites and 77.9 months for African Americans. After accounting for the effect of comorbidities, African American race was statistically significantly associated with breast cancer-specific mortality (African Americans vs non-Hispanic whites: 26.0% vs 17.5%, P = .028; hazard ratio [HR] of death = 1.64, 95% confidence interval [CI] = 1.06 to 2.55). Adjustment for age at diagnosis, clinical stage, and hormone receptor status attenuated the effect, and the effect of race on breast cancer-specific survival was no longer statistically significant (HR of death from breast cancer = 1.43, 95% CI = 0.89 to 2.30). After adjustment for sociodemographic factors, the hazard ratio for race was further attenuated (HR = 1.26; 95% CI = 0.79 to 2.00). CONCLUSIONS: In this underinsured population, African American patients had poorer breast cancer-specific survival than non-Hispanic white patients. After adjustment for clinical and sociodemographic factors, the effect of race on survival was no longer statistically significant.

The effect of dedicated breast surgeons on the short-term outcomes in breast cancer.

OBJECTIVE: The impact of breast surgeons on short-term outcomes in breast cancer care was compared at a single institution. SUMMARY BACKGROUND DATA: Many studies have demonstrated a correlation between high procedural volume and lower mortality in technically challenging procedures. Breast cancer treatment has significant impact on patient behavior, psychology, and appearance. Therefore, evaluation of outcomes cannot be limited to only operative mortality and morbidity. We sought to determine the effect of dedicated breast cancer surgeons on short-term outcomes at a single institution. METHODS: Wishard Memorial Hospital is the county hospital affiliated with the Indiana University School of Medicine. A retrospective review was performed of all patients from January 1, 1997, to February 28, 2006. On July 1, 2003, coverage for the Breast Clinic was changed from general surgeons (G) to breast surgeons (B). There were 596 patients included in the study period. RESULTS: There were no significant differences in patient demographics or disease characteristics between the 2 time periods. For early stage (stage I and II) breast cancer, a higher percentage of patients underwent breast conservation in the breast surgeon period than in the general surgeon period (P = 0.04). Lumpectomy margins in breast conserving operations during the G period were more often positive (P = 0.025) or close (<1 mm) (P = 0.01). Similarly, the rates of re-excision lumpectomy were also significantly lower during the B period (21% vs. 39%, respectively, P = 0.01). Breast surgeons were more likely to perform the sentinel node procedure (P = 0.001). There were no differences in the use of adjuvant chemotherapy and radiation therapy. The use of hormonal manipulation, however, was significantly higher in the B group than in the G group (P < 0.0002). CONCLUSIONS: Surgeons specialized in diseases of the breast demonstrate significant improvement in short-term outcomes associated with breast cancer treatment at a single institution. The differences identified cannot be attributed to differences in institutional function, patient population, surgeon case volume, or on the influence of nonsurgeon physicians.