A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer.

PurposeCabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib.MethodsThis was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent cabozantinib 100 mg qd vs cabozantinib 100 mg qd and erlotinib 50 mg qd (phase I MTD), with a primary objective of estimating objective response rate (ORR).ResultsSixty-four patients were treated in phase I. Doses of 100 mg cabozantinib plus 50 mg erlotinib, or 40 mg cabozantinib plus 150 mg erlotinib were determined to be MTDs. Diarrhea was the most frequent dose-limiting toxicity and the most frequent AE (87.5% of patients). The ORR for phase I was 8.2% (90% CI 3.3-16.5). In phase II, one patient in the cabozantinib arm (N = 15) experienced a partial response, for an ORR of 6.7% (90% CI 0.3-27.9), with no responses for cabozantinib plus erlotinib (N = 13). There was no evidence that co-administration of cabozantinib markedly altered erlotinib pharmacokinetics or vice versa.ConclusionsDespite responses with cabozantinib/erlotinib in phase I, there were no responses in the combination arm of phase II in patients with acquired resistance to erlotinib. Cabozantinib did not appear to re-sensitize these patients to erlotinib

Detection of Dysplasia in Barrett's Esophagus With In Vivo Depth-Resolved Nuclear Morphology Measurements

Patients with Barrett’s esophagus (BE) show increased risk for developing esophageal adenocarcinoma and are routinely examined using upper endoscopy with biopsy to search for neoplastic changes. Angle-resolved low coherence interferometry (a/LCI) uses in vivo depth-resolved nuclear morphology measurements to detect dysplasia. We assessed the clinical utility of a/LCI in the endoscopic surveillance of BE patients

The Ontario Mother and Infant Study (TOMIS) III: A multi-site cohort study of the impact of delivery method on health, service use, and costs of care in the first postpartum year

Abstract Background The caesarean section rate continues to rise globally. A caesarean section is inarguably the preferred method of delivery when there is good evidence that a vaginal delivery may unduly risk the health of a woman or her infant. Any decisions about delivery method in the absence of clear medical indication should be based on knowledge of outcomes associated with different childbirth methods. However, there is lack of sold evidence of the short-term and long-term risks and benefits of a planned caesarean delivery compared to a planned vaginal delivery. It also is important to consider the economic aspects of caesarean sections, but very little attention has been given to health care system costs that take into account services used by women for themselves and their infants following hospital discharge. Methods and design The Ontario Mother and Infant Study III is a prospective cohort study to examine relationships between method of delivery and maternal and infant health, service utilization, and cost of care at three time points during the year following postpartum hospital discharge. Over 2500 women were recruited from 11 hospitals across the province of Ontario, Canada, with data collection occurring between April 2006 and October 2008. Participants completed a self-report questionnaire in hospital and structured telephone interviews at 6 weeks, 6 months, and 12 months after discharge. Data will be analyzed using generalized estimating equation, a special generalized linear models technique. A qualitative descriptive component supplements the survey approach, with the goal of assisting in interpretation of data and providing explanations for trends in the findings. Discussion The findings can be incorporated into patient counselling and discussions about the advantages and disadvantages of different delivery methods, potentially leading to changes in preferences and practices. In addition, the findings will be useful to hospital- and community-based postpartum care providers, managers, and administrators in guiding risk assessment and early intervention strategies. Finally, the research findings can provide the basis for policy modification and implementation strategies to improve outcomes and reduce costs of care

The Amniotic Fluid Index and Oligohydramnios: A Deeper Dive into the Shallow End

Second and third trimester obstetrical ultrasound examinations include an amniotic fluid volume assessment. Professional organizations\u27 clinical guidance recommends using semi-quantitative techniques such as the single deepest vertical pocket or amniotic fluid index for this purpose. The single deepest vertical pocket is described as the preferred method of assessing amniotic fluid volume based on fewer oligohydramnios diagnoses and labor inductions with no demonstrable differences in pregnancy outcomes compared to the amniotic fluid index. We offer an alternative interpretation of the evidence for this advice, drawn from six randomized clinical trials and two meta-analyses comparing the single deepest vertical pocket to the amniotic fluid index. Individually and collectively, these reports are underpowered to detect significant differences in maternal and perinatal outcomes by study group. Moreover, randomized clinical trials comparing maternal and perinatal outcomes resulting from a policy of labor induction at or beyond 37 weeks\u27 gestation versus expectant care consistently favor labor induction, the very intervention paradoxically cited as favoring the single deepest vertical pocket over the amniotic fluid index. We conclude that the amniotic fluid index should be considered a reasonable method for third-trimester amniotic fluid assessment and diagnosing oligohydramnios

Second-Trimester Ultrasound-Measured Umbilical Cord Insertion-to-Placental Edge Distance: Determining an Outcome-Based Threshold for Identifying Marginal Cord Insertions.

OBJECTIVES: We sought to study potential diagnostic criteria for marginal placental cord insertions as determined by associations with obstetric outcomes. METHODS: This single-center retrospective cohort investigation included singleton gestations delivering from January 1, 2012, to December 31, 2016, and having a standard or detailed fetal ultrasound examination from 18 weeks to 21 weeks 6 days. Cord insertion-to-placental edge distances were used to create a referent comparison group and 3 patient groups: greater than 3.0 cm (comparison); greater than 2.0 to 3.0 cm (group 1); greater than 1.0 to 2.0 cm (group 2); and 1.0 cm or less (group 3). The primary outcome consisted of any one of spontaneous delivery before 37 weeks, fetal growth restriction, oligohydramnios, placental abruption, or intrauterine fetal demise. RESULTS: The numbers of participants and mean distances ± SDs for the comparison group and groups 1 to 3, respectively, were 628 and 4.68 ± 1.17 cm, 106 and 2.52 ± 0.26 cm, 131 and 1.60 ± 0.29 cm, and 77 and 0.36 ± 0.37 cm, respectively. The primary outcome was significantly associated only with cord insertion-to-placental edge distances of 1.0 cm or less (adjusted odds ratio, 3.05; 95% confidence interval, 1.73-5.38). CONCLUSIONS: Marginal cord insertions may be diagnosed when the cord insertion-to-placental edge distance is 1.0 cm or less

Preparing a research presentation: a guide for investigators.

Many obstetrics and gynecology residencies require trainees to complete a research project as a graduation requirement. These projects may be submitted for publication in a peer-review journal or presentation at a professional meeting. Although written instructions are available for novice authors, few references target research abstract submission and presentation. This paper provides investigators with the advice to successfully negotiate this process

Cervical evaluation in pregnancy: proper measurement, evaluation, and management.

Preterm birth is the leading cause of perinatal morbidity and mortality in developed nations. The heterogeneous causes of spontaneous preterm birth make prediction and prevention difficult. The primary importance of transvaginal cervical sonography and cervicovaginal fetal fibronectin lies in their high negative predictive values in assessing risk for preterm birth. Cervical length may be useful in identifying women who are candidates for cervical cerclage or progesterone therapy for preterm birth prevention. Together, cervical length and fibronectin can be used in the triaging of women symptomatic for preterm labor

Workplace Violence in Health Care--It\u27s Not Part of the Job .

IMPORTANCE: While health care workers comprise just 13% of the US workforce, they experience 60% of all workplace assaults. This violence is the second leading cause of fatal occupational injury. Women comprise 45% of the US labor force but 80% of health care workers, the highest proportion of females in any industry. OBJECTIVE: The purpose was to describe the prevalence, forms, and consequences of health care workplace violence (WPV). The role and components of prevention programs for avoiding or mitigating violence are discussed, including opportunities for participation by obstetrician-gynecologists. EVIDENCE ACQUISITION: A search of PubMed from 1990 to February 1, 2016, identified relevant manuscripts. Additional studies were found by reviewing the manuscripts\u27 references. Government Web sites were visited for relevant data, publications, and resources. RESULTS: Health care WPV continues to rise despite an overall decrease in US WPV. While workers are most likely to be assaulted by clients or patients, they are most frequently bullied and threatened by coworkers. All incidents are markedly underreported in the absence of physical injury or lost work time. Sequelae include physical and psychological trauma, adverse patient outcomes, and perceived lower quality of care. CONCLUSIONS: The human, societal, and economic costs of health care WPV are enormous and unacceptable. Comprehensive prevention, planning, and intervention offer the best means of mitigating risks. As women\u27s health physicians and health care workers, obstetrician-gynecologists should be encouraged to participate in such efforts