Cancer biomarkers: Emerging trends and clinical implications for personalized treatment.

The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of cancer patients. The development of personalized medicine represents a turning point and a new paradigm in cancer management, as biomarkers enable oncologists to tailor treatments based on the unique molecular profile of each patient's tumor. In this review, we discuss the scientific milestones of cancer biomarkers and explore future possibilities to improve the management of patients with solid tumors. This progress is primarily attributed to the biological characterization of cancers, advancements in testing methodologies, elucidation of the immune microenvironment, and the ability to profile circulating tumor fractions. Integrating these insights promises to continually advance the precision oncology field, fostering better patient outcomes.

Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition.

Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.

Integrating genomic features for non-invasive early lung cancer detection.

Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.

New labor curves of dilation and station to improve the accuracy of predicting labor progress.

BACKGROUND: The diagnosis of failure to progress, the most common indication for intrapartum cesarean delivery, is based on the assessment of cervical dilation and station over time. Labor curves serve as references for expected changes in dilation and fetal descent. The labor curves of Friedman, Zhang et al, and others are based on time alone and derived from mothers with spontaneous labor onset. However, labor induction is now common, and clinicians also consider other factors when assessing labor progress. Labor curves that consider the use of labor induction and other factors that influence labor progress have the potential to be more accurate and closer to clinical decision-making. OBJECTIVE: This study aimed to compare the prediction errors of labor curves based on a single factor (time) or multiple clinically relevant factors using two modeling methods: mixed-effects regression, a standard statistical method, and Gaussian processes, a machine learning method. STUDY DESIGN: This was a longitudinal cohort study of changes in dilation and station based on data from 8022 births in nulliparous women with a live, singleton, vertex-presenting fetus ≥35 weeks of gestation with a vaginal delivery. New labor curves of dilation and station were generated with 10-fold cross-validation. External validation was performed using a geographically independent group. Model variables included time from the first examination in the 20 hours before delivery; dilation, effacement, and station recorded at the previous examination; cumulative contraction counts; and use of epidural anesthesia and labor induction. To assess model accuracy, differences between each model's predicted value and its corresponding observed value were calculated. These prediction errors were summarized using mean absolute error and root mean squared error statistics. RESULTS: Dilation curves based on multiple parameters were more accurate than those derived from time alone. The mean absolute error of the multifactor methods was better (lower) than those of the single-factor methods (0.826 cm [95% confidence interval, 0.820-0.832] for the multifactor machine learning and 0.893 cm [95% confidence interval, 0.885-0.901] for the multifactor mixed-effects method and 2.122 cm [95% confidence interval, 2.108-2.136] for the single-factor methods; P<.0001 for both comparisons). The root mean squared errors of the multifactor methods were also better (lower) than those of the single-factor methods (1.126 cm [95% confidence interval, 1.118-1.133] for the machine learning [P<.0001] and 1.172 cm [95% confidence interval, 1.164-1.181] for the mixed-effects methods and 2.504 cm [95% confidence interval, 2.487-2.521] for the single-factor [P<.0001 for both comparisons]). The multifactor machine learning dilation models showed small but statistically significant improvements in accuracy compared to the mixed-effects regression models (P<.0001). The multifactor machine learning method produced a curve of descent with a mean absolute error of 0.512 cm (95% confidence interval, 0.509-0.515) and a root mean squared error of 0.660 cm (95% confidence interval, 0.655-0.666). External validation using independent data produced similar findings. CONCLUSION: Cervical dilation models based on multiple clinically relevant parameters showed improved (lower) prediction errors compared to models based on time alone. The mean prediction errors were reduced by more than 50%. A more accurate assessment of departure from expected dilation and station may help clinicians optimize intrapartum management.

Examining Attitudes Towards Mental Health Diagnoses: A Q-Methodology Study.

BACKGROUND: Debates exist regarding the validity and utility of functional psychiatric diagnoses. How mental health diagnoses are understood has real impacts for service users and service delivery. AIMS: To investigate different attitudes about the utility of psychiatric diagnoses. METHODS: Forty-one stakeholders sorted 57 statements related to the usefulness of psychiatric diagnoses. Using q-methodology, four viewpoints were identified and interpreted. RESULTS: Viewpoint 1 (Pathologising human experience) regarded diagnoses as pseudo-scientific constructs that lacked validity and obscured the relationships between lived experience and distress. Viewpoint 2 (Illnesses like any other) held that labels reflected real disorders and diagnosis offered important benefits for service users and services. Viewpoint 3 (Stigmatised conditions) similarly regarded diagnoses as reflecting real disorders, but diagnostic criteria were viewed as biased and the impacts of applying labels seen as causing problems for service users. Conversely, Viewpoint 4 (Useful short-hands) viewed diagnostic processes as imperfect but necessary for supporting communication and structuring service delivery. CONCLUSIONS: While not all viewpoints are in keeping with empirical evidence, we hope results will enable professionals and service users to take meta-positions in relation to their own and others' attitudes, and to reflect on the impacts of privileging certain viewpoints over others.

The evolution of the labor curve and its implications for clinical practice: the relationship between cervical dilation, station, and time during labor.

The assessment of labor progress is germane to every woman in labor. Two labor disorders-arrest of dilation and arrest of descent-are the primary indications for surgery in close to 50% of all intrapartum cesarean deliveries and are often contributing indications for cesarean deliveries for fetal heart rate abnormalities. Beginning in 1954, the assessment of labor progress was transformed by Friedman. He published a series of seminal works describing the relationship between cervical dilation, station of the presenting part, and time. He proposed nomenclature for the classification of labor disorders. Generations of obstetricians used this terminology and normal labor curves to determine expected rates of dilation and fetal descent and to decide when intervention was required. The analysis of labor progress presents many mathematical challenges. Clinical measurements of dilation and station are imprecise and prone to variation, especially for inexperienced observers. Many interrelated factors influence how the cervix dilates and how the fetus descends. There is substantial variability in when data collection begins and in the frequency of examinations. Statistical methods to account for these issues have advanced considerably in recent decades. In parallel, there is growing recognition among clinicians of the limitations of using time alone to assess progress in cervical dilation in labor. There is wide variation in the patterns of dilation over time and most labors do not follow an average dilation curve. Reliable assessment of labor progression is important because uncertainty leads to both over-use and under-use of cesarean delivery and neither of these extremes are desirable. This review traces the evolution of labor curves, describes how limitations are being addressed to reduce uncertainty and to improve the assessment of labor progression using modern statistical techniques and multi-dimensional data, and discusses the implications for obstetrical practice.

Perinatal Outcome following the Suspension of Intrapartum Oxygen Treatment.

OBJECTIVE: This study aimed to evaluate whether the suspension of intrapartum maternal oxygen supplementation for nonreassuring fetal heart rate is associated with adverse perinatal outcomes. STUDY DESIGN: A retrospective cohort study, including all individuals that underwent labor in a single tertiary medical center. On April 16, 2020, the routine use of intrapartum oxygen for category II and III fetal heart rate tracings was suspended. The study group included individuals with singleton pregnancies that underwent labor during the 7 months between April 16, 2020, and November 14, 2020. The control group included individuals that underwent labor during the 7 months before April 16, 2020. Exclusion criteria included elective cesarean section, multifetal pregnancy, fetal death, and maternal oxygen saturation <95% during delivery. The primary outcome was defined as the rate of composite neonatal outcome, consisting of arterial cord pH <7.1, mechanical ventilation, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage grade 3/4, and neonatal death. The secondary outcome was the rate of cesarean and operative delivery. RESULTS: The study group included 4,932 individuals, compared with 4,906 individuals in the control group. The suspension of intrapartum oxygen treatment was associated with a significant increase in the rate of composite neonatal outcome (187 [3.8%] vs. 120 [2.4%], p < 0.001), including the rate of abnormal cord arterial pH <7.1 (119 [2.4%] vs. 56 [1.1%], p < 0.01). A higher rate of cesarean section due to nonreassuring fetal heart rate was noted in the study group (320 [6.5%] vs. 268 [5.5%], p = 0.03).A logistic regression analysis revealed that the suspension of intrapartum oxygen treatment was independently associated with the composite neonatal outcome (adjusted odds ratio = 1.55 [95% confidence interval, 1.23-1.96]) while adjusting for suspected chorioamnionitis, intrauterine growth restriction, and recent coronavirus disease 2019 exposure. CONCLUSION: Suspension of intrapartum oxygen treatment for nonreassuring fetal heart rate was associated with higher rates of adverse neonatal outcomes and urgent cesarean section due to fetal heart rate. KEY POINTS: · The available data on intrapartum maternal oxygen supplementation are equivocal.. · Suspension of maternal oxygen for nonreassuring fetal heart rate during labor was associated with adverse neonatal outcomes.. · Oxygen treatment might still be important and relevant during labor..

Circulating Tumor DNA Analysis for Detection of Minimal Residual Disease After Chemoradiotherapy for Localized Esophageal Cancer.

BACKGROUND & AIMS: Biomarkers are needed to risk stratify after chemoradiotherapy for localized esophageal cancer. These could improve identification of patients at risk for cancer progression and selection of additional therapy. METHODS: We performed deep sequencing (CAncer Personalized Profiling by deep Sequencing, [CAPP-Seq]) analyses of plasma cell-free DNA collected from 45 patients before and after chemoradiotherapy for esophageal cancer, as well as DNA from leukocytes and fixed esophageal tumor biopsy samples collected during esophagogastroduodenoscopy. Patients were treated from May 2010 through October 2015; 23 patients subsequently underwent esophagectomy, and 22 did not undergo surgery. We also sequenced DNA from blood samples from 40 healthy control individuals. We analyzed 802 regions of 607 genes for single-nucleotide variants previously associated with esophageal adenocarcinoma or squamous cell carcinoma. Patients underwent imaging analyses 6-8 weeks after chemoradiotherapy and were followed for 5 years. Our primary aim was to determine whether detection of circulating tumor DNA (ctDNA) after chemoradiotherapy is associated with risk of tumor progression (growth of local, regional, or distant tumors, detected by imaging or biopsy). RESULTS: The median proportion of tumor-derived DNA in total cell-free DNA before treatment was 0.07%, indicating that ultrasensitive assays are needed for quantification and analysis of ctDNA from localized esophageal tumors. Detection of ctDNA after chemoradiotherapy was associated with tumor progression (hazard ratio, 18.7; P < .0001), formation of distant metastases (hazard ratio, 32.1; P < .0001), and shorter disease-specific survival times (hazard ratio, 23.1; P < .0001). A higher proportion of patients with tumor progression had new mutations detected in plasma samples collected after chemoradiotherapy than patients without progression (P = .03). Detection of ctDNA after chemoradiotherapy preceded radiographic evidence of tumor progression by an average of 2.8 months. Among patients who received chemoradiotherapy without surgery, combined ctDNA and metabolic imaging analysis predicted progression in 100% of patients with tumor progression, compared with 71% for only ctDNA detection and 57% for only metabolic imaging analysis (P < .001 for comparison of either technique to combined analysis). CONCLUSIONS: In an analysis of cell-free DNA in blood samples from patients who underwent chemoradiotherapy for esophageal cancer, detection of ctDNA was associated with tumor progression, metastasis, and disease-specific survival. Analysis of ctDNA might be used to identify patients at highest risk for tumor progression.

Fifteen-minute consultation: How to undertake an effective video consultation for children, young people and their families.

The COVID-19 pandemic has changed how we work in paediatrics with increasing use of virtual consultations. When optimised, a great deal can be achieved through video consultation compared with telephone, but accessibility and clinical risk need to be carefully considered and managed. This article aims to provide a structured approach with top tips for planning and delivering video consultations effectively in paediatrics.

An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues.

We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content. The Omni-ATAC protocol generates chromatin accessibility profiles from archival frozen tissue samples and 50-µm sections, revealing the activities of disease-associated DNA elements in distinct human brain structures. The Omni-ATAC protocol enables the interrogation of personal regulomes in tissue context and translational studies.

In-vitro maturation of oocytes recovered during cryopreservation of pre-pubertal girls undergoing fertility preservation.

RESEARCH QUESTION: In-vitro maturation (IVM) of oocytes recovered during ovarian tissue cryopreservation (OTC) is often practised, although it is still considered experimental. To date, only a few studies have examined the success of this maturation process in pre-menarche girls. The aim of this study was to examine the outcomes of IVM of oocytes recovered during OTC in pre-menarche patients scheduled for onco-therapy. DESIGN: A retrospective cohort study in a tertiary university-affiliated hospital. A total of 93 patients aged 0-25 years who underwent OTC as part of onco-fertility preservation between 2007 and 2019 were included in the study. Oocytes were recovered from the medium after OTC and matured over 48 h. Oocyte development and maturation rate were recorded and compared between different age groups. RESULTS: Patient's age was not correlated linearly with the total number of mature oocytes R = 0.2. The absolute maturation rate in post-menarche and pre-menarche patients differed significantly (38.0% versus 25.3%, respectively; P > 0.001), whereas the degeneration rate of the oocytes did not (39.8% versus 33.5%; P = 0.167). The pre-menarche group had significantly lower mean number of metaphase II oocytes compared with the post-menarche group (2.8 [±2.3] versus 5.6 [±4.6]; P = 0.01; 95% CI -4.62 to -0.46). Oocytes recovered from patients aged 1-5 years demonstrated low maturation rate. CONCLUSIONS: Oocytes recovered from pre-menarche girls, and especially those younger than the age of 5 years who undergo fertility preservation, have a lower chance of reaching maturity in IVM compared with older women. This may indicate a need for alternative methods for preserving fertility in these young patients.

"Doing something" about the cesarean delivery rate.

There is a general consensus that the cesarean delivery rate in the United States is too high, and that practice patterns of obstetricians are largely to blame for this situation. In reality, the US cesarean delivery rate is the result of 3 forces largely beyond the control of the practicing clinician: patient expectations and misconceptions regarding the safety of labor, the medical-legal system, and limitations in technology. Efforts to "do something" about the cesarean delivery rate by promulgating practice directives that are marginally evidence-based or influenced by social pressures are both ineffective and potentially harmful. We examine both the recent American Congress of Obstetricians and Gynecologists (ACOG)/Society for Maternal-Fetal Medicine Care Consensus Statement "Safe Prevention of Primary Cesarean Delivery" document and the various iterations of the ACOG guidelines for vaginal birth after cesarean delivery in this context. Adherence to arbitrary time limits for active phase or second-stage arrest without incorporating other clinical factors into the decision-making process is unwise. In a similar manner, ever-changing practice standards for vaginal birth after cesarean driven by factors other than changing data are unlikely to be effective in lowering the cesarean delivery rate. Whether too high or too low, the current US cesarean delivery rate is the expected result of the unique demographic, geographic, and social forces driving it and is unlikely to change significantly given the limitations of current technology to otherwise satisfy the demands of these forces.

The limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia.

BACKGROUND: Despite intensive efforts directed at initial training in fetal heart rate interpretation, continuing medical education, board certification/recertification, team training, and the development of specific protocols for the management of abnormal fetal heart rate patterns, the goals of consistently preventing hypoxia-induced fetal metabolic acidemia and neurologic injury remain elusive. OBJECTIVE: The purpose of this study was to validate a recently published algorithm for the management of category II fetal heart rate tracings, to examine reasons for the birth of infants with significant metabolic acidemia despite the use of electronic fetal heart rate monitoring, and to examine critically the limits of electronic fetal heart rate monitoring in the prevention of neonatal metabolic acidemia. STUDY DESIGN: The potential performance of electronic fetal heart rate monitoring under ideal circumstances was evaluated in an outcomes-blinded examination fetal heart rate tracing of infants with metabolic acidemia at birth (base deficit, >12) and matched control infants (base deficit, <8) under the following conditions: (1) expert primary interpretation, (2) use of a published algorithm that was developed and endorsed by a large group of national experts, (3) assumption of a 30-minute period of evaluation for noncritical category II fetal heart rate tracings, followed by delivery within 30 minutes, (4) evaluation without the need to provide patient care simultaneously, and (5) comparison of results under these circumstances with those achieved in actual clinical practice. RESULTS: During the study period, 120 infants were identified with an arterial cord blood base deficit of >12 mM/L. Matched control infants were not demographically different from subjects. In actual practice, operative intervention on the basis of an abnormal fetal heart rate tracings occurred in 36 of 120 fetuses (30.0%) with metabolic acidemia. Based on expert, algorithm-assisted reviews, 55 of 120 patients with acidemia (45.8%) were judged to need operative intervention for abnormal fetal heart rate tracings. This difference was significant (P=.016). In infants who were born with a base deficit of >12 mM/L in which blinded, algorithm-assisted expert review indicated the need for operative delivery, the decision for delivery would have been made an average of 131 minutes before the actual delivery. The rate of expert intervention for fetal heart rate concerns in the nonacidemic control group (22/120; 18.3%) was similar to the actual intervention rate (23/120; 19.2%; P=1.0) Expert review did not mandate earlier delivery in 65 of 120 patients with metabolic acidemia. The primary features of these 65 cases included the occurrence of sentinel events with prolonged deceleration just before delivery, the rapid deterioration of nonemergent category II fetal heart rate tracings before realistic time frames for recognition and intervention, and the failure of recognized fetal heart rate patterns such as variability to identify metabolic acidemia. CONCLUSIONS: Expert, algorithm-assisted fetal heart rate interpretation has the potential to improve standard clinical performance by facilitating significantly earlier recognition of some tracings that are associated with metabolic acidemia without increasing the rate of operative intervention. However, this improvement is modest. Of infants who are born with metabolic acidemia, only approximately one-half potentially could be identified and have delivery expedited even under ideal circumstances, which are probably not realistic in current US practice. This represents the limits of electronic fetal heart rate monitoring performance. Additional technologies will be necessary if the goal of the prevention of neonatal metabolic acidemia is to be realized.

Assessing first-stage labor progression and its relationship to complications.

BACKGROUND: New labor curves have challenged the traditional understanding of the general pattern of dilation and descent in labor. They also revealed wide variation in the time to advance in dilation. An interval of arrest such as 4 hours did not fall beyond normal limits until dilation had reached 6 cm. Thus, the American College of Obstetricians and Gynecologists/Society for Maternal-Fetal Medicine first-stage arrest criteria, based in part on these findings, are applicable only in late labor. The wide range of time to dilate is unavoidable because cervical dilation has neither a precise nor direct relationship to time. Newer statistical techniques (multifactorial models) can improve precision by incorporating several factors that are related directly to labor progress. At each examination, the calculations adapt to the mother's current labor conditions. They produce a quantitative assessment that is expressed in percentiles. Low percentiles indicate potentially problematic labor progression. OBJECTIVE: The purpose of this study was to assess the relationship between first-stage labor progress- and labor-related complications with the use of 2 different assessment methods. The first method was based on arrest of dilation definitions. The other method used percentile rankings of dilation or station based on adaptive multifactorial models. STUDY DESIGN: We included all 4703 cephalic-presenting, term, singleton births with electronic fetal monitoring and cord gases at 2 academic community referral hospitals in 2012 and 2013. We assessed electronic data for route of delivery, all dilation and station examinations, newborn infant status, electronic fetal monitoring tracings, and cord blood gases. The labor-related complication groups included 272 women with cesarean delivery for first-stage arrest, 558 with cesarean delivery for fetal heart rate concerns, 178 with obstetric hemorrhage, and 237 with neonatal depression, which left 3004 women in the spontaneous vaginal birth group. Receiver operating characteristic curves were constructed for each assessment method by measurement of the sensitivity for each complication vs the false-positive rate in the normal reference group. RESULTS: The duration of arrest at ≥6 cm dilation showed poor levels of discrimination for the cesarean delivery interventions (area under the curve, 0.55-0.65; P < .01) and no significant relationship to hemorrhage or neonatal depression. The dilation and station percentiles showed high discrimination for the cesarean delivery-related outcomes (area under the curve, 0.78-0.93; P < .01) and low discrimination for the clinical outcomes of hemorrhage and neonatal depression (area under the curve, 0.58-0.61; P < .01). CONCLUSIONS: Duration of arrest of dilation at ≥6 cm showed little or no discrimination for any of the complications. In comparison, percentile rankings that were based on the adaptive multifactorial models showed much higher discrimination for cesarean delivery interventions and better, but low discrimination for hemorrhage. Adaptive multifactorial models present a different method to assess labor progress. Rather than "pass/fail" criteria that are applicable only to dilation in late labor, they produce percentile rankings, assess 2 essential processes for vaginal birth (dilation and descent), and can be applied from 3 cm onward. Given the limitations of labor-progress assessment based solely on the passage of time and because of the extreme variation in decision-making for cesarean delivery for labor disorders, the types of mathematic analyses that are described in this article are logical and promising steps to help standardize labor assessment.

Descent of the fetal head (station) during the first stage of labor.

BACKGROUND: High station at specific points in the first stage of labor, such as a floating head on admission, or at 4-cm dilation or when arrest of dilation occurs, is associated with higher rates of failure to deliver vaginally. Therefore it could be useful to know if station is within an expected range at a given dilation during first stage. Arrest of descent disorders have been defined thus far on criteria applicable in the second stage. Statistical modeling is an attractive methodology to characterize the relationship between station and dilation because the resulting mathematical expressions could be used as a reference for comparison in the future. In addition, they can be used to produce a finely graded assessment of descent using numerical terms such as percentile rankings. A 2-step approach to potentially improving the assessment of station could be to develop a statistical model that describes the general relationship between station and dilation in the first stage of uncomplicated births and then determine if such a model would have identified births with complications related to poor labor progress. Given the complex nature of labor data, especially the imprecision of dilation and station measurement, it is not immediately evident that such a model is identifiable or what its precision would be. OBJECTIVE: We sought to characterize in mathematical terms the relationship of station to dilation during the first stage of labor for nulliparous and multiparous women with spontaneous vaginal births. STUDY DESIGN: This retrospective cohort study included 28,121 exams from 5555 women with singleton cephalic presentations at ≥37 weeks' gestation with electronic fetal monitoring tracings, who delivered vaginally without instrumentation and had 5-minute Apgar scores >6 at 2 academic community referral hospitals in 2012 through 2013. Women with a previous cesarean birth were excluded. We used longitudinal statistical techniques suitable to biological data that were irregularly sampled with repeated measures over time. RESULTS: A linear relationship was observed between station and dilation. For both nulliparous and multiparous women the final model was a linear regression with random effects for intercept and slope and a first-order autoregressive correlation structure. The 5th-95th range of station at any given dilation spanned about 3-4 cm. CONCLUSION: Our results demonstrate a general trend of increasing descent of the presenting part as dilation advances during the first stage of labor in women who delivered vaginally without instrumentation. We propose that the mathematical expressions describing this relationship may be valuable in the assessment of first-stage labor progression.

Travel medicine updates for the NP.

ABSTRACT: This article provides an overview of the approach to preparing patients for travel, including travel counseling and risk mitigation through vaccination and chemoprophylaxis. Although some patients require referral for consultation with a travel medicine specialist, others can be managed by their primary care provider. In this article, traveler's diarrhea, updated travel-related immunizations, and malaria prophylaxis are discussed.

Data-Driven Insights into Labor Progression with Gaussian Processes.

Clinicians routinely perform pelvic examinations to assess the progress of labor. Clinical guidelines to interpret these examinations, using time-based models of cervical dilation, are not always followed and have not contributed to reducing cesarean-section rates. We present a novel Gaussian process model of labor progress, suitable for real-time use, that predicts cervical dilation and fetal station based on clinically relevant predictors available from the pelvic exam and cardiotocography. We show that the model is more accurate than a statistical approach using a mixed-effects model. In addition, it provides confidence estimates on the prediction, calibrated to the specific delivery. Finally, we show that predicting both dilation and station with a single Gaussian process model is more accurate than two separate models with single predictions.

Construction of a comprehensive fetal monitoring database for the study of perinatal hypoxic ischemic encephalopathy.

This article describes the methods used to build a large-scale database of more than 250,000 electronic fetal monitoring (EFM) records linked to a comprehensive set of clinical information about the infant, the mother, the pregnancy, labor, and outcome. The database can be used to investigate how birth outcome is related to clinical and EFM features. The main steps involved in building the database were: (1) Acquiring the raw EFM recording and clinical records for each birth. (2) Assigning each birth to an objectively defined outcome class that included normal, acidosis, and hypoxic-ischemic encephalopathy. (3) Removing all personal health information from the EFM recordings and clinical records. (4) Preprocessing the deidentified EFM records to eliminate duplicates, reformat the signals, combine signals from different sensors, and bridge gaps to generate signals in a format that can be readily analyzed. (5) Post-processing the repaired EFM recordings to extract key features of the fetal heart rate, uterine activity, and their relations. (6) Populating a database that links the clinical information, EFM records, and EFM features to support easy querying and retrieval. •A multi-step process is required to build a comprehensive database linking electronic temporal fetal monitoring signals to a comprehensive set of clinical information about the infant, the mother, the pregnancy, labor, and outcome.•The current database documents more than 250,000 births including almost 4,000 acidosis and 400 HIE cases. This represents more than 80% of the births that occurred in 15 Northern California Kaiser Permanente Hospitals between 2011-2019. This is a valuable resource for studying the factors predictive of outcome.•The signal processing code and schemas for the database are freely available. The database will not be permitted to leave Kaiser firewalls, but a process is in place to allow interested investigators to access it.