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Abstract Both hyperthyroidism and hypothyroidism can have adverse effects in pregnancy. The most common causes of thyrotoxicosis in pregnancy are gestational transient thyrotoxicosis and Graves’ disease. It is important to distinguish between these entities as treatment options differ. Women of reproductive age who are diagnosed with Graves’ disease should be counseled regarding the impact of treatment options on a potential pregnancy. Although the absolute risk is small, antithyroid medications can have teratogenic effects. Propylthiouracil appears to have less severe teratogenicity compared to methimazole and is therefore favored during the first trimester if a medication is needed. Women should be advised to delay pregnancy for at least 6 months following radioactive iodine to minimize potential adverse effects from radiation and ensure normal thyroid hormone levels prior to conception. As thyroid hormone is critical for normal fetal development, hypothyroidism is associated with adverse obstetric and child neurodevelopmental outcomes. Women with overt hypothyroidism should be treated with levothyroxine (LT4) to a thyrotropin (thyroid-stimulating hormone; TSH) goal of <2.5 mIU/L. There is mounting evidence for associations of maternal hypothyroxinemia and subclinical hypothyroidism with pregnancy loss, preterm labor, and lower scores on child cognitive assessment. Although there is minimal risk of LT4 treatment to keep TSH within the pregnancy-specific reference range, treatment of mild maternal thyroid hypofunction remains controversial, given the lack of clinical trials showing improved outcomes with LT4 treatment.

Placenta accreta spectrum (PAS) is a high-risk obstetrical condition associated with significant morbidity and mortality. Current clinical screening modalities for PAS are not always conclusive. Here, we report a nanostructure-embedded microchip that efficiently enriches both single and clustered circulating trophoblasts (cTBs) from maternal blood for detecting PAS. We discover a uniquely high prevalence of cTB-clusters in PAS and subsequently optimize the device to preserve the intactness of these clusters. Our feasibility study on the enumeration of cTBs and cTB-clusters from 168 pregnant women demonstrates excellent diagnostic performance for distinguishing PAS from non-PAS. A logistic regression model is constructed using a training cohort and then cross-validated and tested using an independent cohort. The combined cTB assay achieves an Area Under ROC Curve of 0.942 (throughout gestation) and 0.924 (early gestation) for distinguishing PAS from non-PAS. Our assay holds the potential to improve current diagnostic modalities for the early detection of PAS. Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.

The objective of this study was to test a screening model that employs the Rapid Interactive Screening Test for Autism in Toddlers (RITA-T), in an underserved community to improve ASD detection. We collaborated with a large Early Intervention (EI) program and trained 4 providers reliably on the RITA-T. Toddlers received the Modified Checklist for Autism in Toddlers (MCHAT-R/F), the RITA-T, developmental and autism testing, and a best-estimate clinical diagnosis. Eighty-One toddlers were enrolled: 57 with ASD and 24 with Developmental Delay (DD) non-ASD. Wait-time for diagnosis was on average 6 weeks. The RITA-T correlated highly with autism measures and EI staff integrated this model easily. The RITA-T significantly improved the identification and wait time for ASD in this underserved community.

To compare costs and efficacy of reflex and recall prenatal DNA screening for trisomy 21, 18 and 13 (affected pregnancies). In both methods women have Combined test markers measured. With recall screening, women with a high Combined test risk are recalled for counselling and offered a DNA blood test or invasive diagnostic testing. With reflex screening, a DNA analysis is automatically performed on plasma collected when blood was collected for measurement of the Combined test markers. Published data were used to estimate, for each method, using various unit costs and risk cut-offs, the cost per woman screened, cost per affected pregnancy diagnosed, and for a given number of women screened, numbers of affected pregnancies diagnosed, unaffected pregnancies with positive results, and women with unaffected pregnancies having invasive diagnostic testing. Cost per woman screened is lower with reflex v recall screening: £37 v £38, and £11,043 v £11,178 per affected pregnancy diagnosed (DNA £250, Combined test markers risk cut-off 1 in 150). Reflex screening results in similar numbers of affected pregnancies diagnosed, with 100-fold fewer false-positives and 20-fold fewer women with unaffected pregnancies having invasive diagnostic testing. Reflex DNA screening is less expensive, more cost-effective, and safer than recall screening.

Background Medical students and professionals often struggle to understand medical test results, which can lead to poor medical decisions. Natural frequency tree-based training (NF-TT) has been suggested to help people correctly estimate the predictive value of medical tests. We aimed to compare the effectiveness of NF-TT with conventional conditional probability formula-based training (CP-FT) and investigate student variables that may influence NF-TT’s effectiveness. Methods We conducted a parallel group randomized controlled trial of NF-TT vs. CP-FT in two medical schools in South Korea (a 1:1 allocation ratio). Participants were randomly assigned to watch either NF-TT or CP-FT video at individual computer stations. NF-TT video showed how to translate relevant probabilistic information into natural frequencies using a tree structure to estimate the predictive values of screening tests. CP-FT video showed how to plug the same information into a mathematical formula to calculate predictive values. Both videos were 15 min long. The primary outcome was the accuracy in estimating the predictive value of screening tests assessed using multiple-choice questions at baseline, post-intervention (i.e., immediately after training), and one-month follow-up. The secondary outcome was the accuracy of conditional probabilistic reasoning in non-medical contexts, also assessed using multiple-choice questions, but only at follow-up as a measure of transfer of learning. 231 medical students completed their participation. Results Overall, NF-TT was not more effective than CP-FT in improving the predictive value estimation accuracy at post-intervention (NF-TT: 87.13%, CP-FT: 86.03%, p  = .86) and follow-up (NF-TT: 72.39%, CP-FT: 68.10%, p  = .40) and facilitating transfer of training (NF-TT: 75.54%, CP-FT: 71.43%, p =  .41). However, for participants without relevant prior training, NF-TT was more effective than CP-FT in improving estimation accuracy at follow-up (NF-TT: 74.86%, CP-FT: 58.71%, p =  .02) and facilitating transfer of learning (NF-TT: 82.86%, CP-FT: 66.13%, p =  .04). Conclusions Introducing NF-TT early in the medical school curriculum, before students are exposed to a pervasive conditional probability formula-based approach, would offer the greatest benefit. Trial registration Korea Disease Control and Prevention Agency Clinical Research Information Service KCT0004246 (the date of first trial registration: 27/08/2019). The full trial protocol can be accessed at https://cris.nih.go.kr/cris/search/detailSearch.do?seq=15616&search_page=L .

Objective: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis in screening for aneuploidies and to explore the potential use of this method in clinical practice. Methods: Searches of PubMed and MEDLINE were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between 2011, when the first such study was published, and 20 December 2013. Results: Weighted pooled detection rates (DR) and false-positive rates (FPR) in singleton pregnancies were 99.0% (95% CI 98.2-99.6) and 0.08% (95% CI 0.03-0.14), respectively, for trisomy 21; 96.8% (95% CI 94.5-98.4) and 0.15% (95% CI 0.08-0.25) for trisomy 18; 92.1% (95% CI 85.9-96.7) and 0.20% (95% CI 0.04-0.46) for trisomy 13; 88.6% (95% CI 83.0-93.1) and 0.12% (95% CI 0.05-0.24) for monosomy X, and 93.8% (95% CI 85.9-98.7) and 0.12% (95% CI 0.02-0.28) for sex chromosome aneuploidies other than monosomy X. For twin pregnancies, the DR was 94.4% (95% 74.2-99.0) and the FPR was 0% (95% CI 0.00-1.84) for trisomy 21. Conclusion: An analysis of cfDNA in maternal blood provides effective screening for trisomies.

Background The Swedish National Board of Health and Welfare (SNBHW) recommended the new diagnostic criteria for GDM based upon Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study thresholds. Due to limited knowledge base, no recommendations were made on GDM screening. The aim of this study is to evaluate test characteristics of risk factors and fasting blood glucose as screening tests for diagnosing GDM using diagnostic thresholds based upon HAPO study 1.75/2.0 (model I/II respectively) odds ratio for adverse pregnancy outcomes. Methods This cross-sectional, population-based study included all pregnant women who attended maternal health care in Örebro County, Sweden between the years 1994–96. A 75 g OGTT with capillary fasting and 2-h blood glucose was offered to all pregnant women at week 28–32. Risk factors and repeated random glucose samples were collected. Sensitivity, specificity and predictive values of blood glucose were calculated. Results Prevalence of GDM was 11.7% with model I and 7.2% with the model II criteria. Risk factors showed 28%, (95% CI 24–32) and 31%, (95% CI 25–37) sensitivity for model I and II respectively. A fasting cut off ≥4.8 mmol/l occurred in 24% of women with 91%, (95% CI 88–94) sensitivity and 85%, (95% CI 83–86) specificity using model I while a fasting cut off ≥5.0 mmol/l occurred in 14% with 91%, (95% CI 87–94) sensitivity and 92%, (95% CI 91–93) specificity using model II. Conclusion Risk factor screening for GDM was found to be poorly predictive of GDM but fasting glucose of 4.8–5.0 mmol/l showed good test characteristics irrespective of diagnostic model and results in a low rate of OGTTs.

A hallmark of high-quality cancer care is the delivery of the right treatment to the right patient at the right time. Precision oncology therapies, which target specific genetic changes in a patient's cancer, are changing the nature of cancer treatment by allowing clinicians to select therapies that are most likely to benefit individual patients. In current clinical practice, oncologists are increasingly formulating cancer treatment plans using results from complex laboratory and imaging tests that characterize the molecular underpinnings of an individual patient's cancer. These molecular fingerprints can be quite complex and heterogeneous, even within a single patient. To enable these molecular tumor characterizations to effectively and safely inform cancer care, the cancer community is working to develop and validate multiparameter omics tests and imaging tests as well as software and computational methods for interpretation of the resulting datasets. To examine opportunities to improve cancer diagnosis and care in the new precision oncology era, the National Cancer Policy Forum developed a two-workshop series. The first workshop focused on patient access to expertise and technologies in oncologic imaging and pathology and was held in February 2018. The second workshop, conducted in collaboration with the Board on Mathematical Sciences and Analytics, was held in October 2018 to examine the use of multidimensional data derived from patients with cancer, and the computational methods that analyze these data to inform cancer treatment decisions. This publication summarizes the presentations and discussions from the second workshop.

Background Understanding healthcare professionals' (HCPs) experiences of caring for women with false‐positive screening test results in the National Health Service Breast Screening Programme (NHSBSP) is important for reducing the impact of such results. Methods Interviews were undertaken with 12 HCPs from a single NHSBSP unit, including advanced radiographer practitioners, breast radiographers, breast radiologists, clinical nurse specialists (CNSs), and a radiology healthcare assistant. Data were analysed thematically using Template Analysis. Results Two themes were produced: (1) Gauging and navigating women's anxiety during screening assessment was an inevitable and necessary task for all participants. CNSs were perceived as particularly adept at this, while breast radiographers reported a lack of adequate formal training. (2) Controlling the delivery of information to women (including amount, type and timing of information). HCPs reported various communication strategies to facilitate women's information processing and retention during a distressing time. Conclusions Women's anxiety could be reduced through dedicated CNS support, but this should not replace support from other HCPs. Breast radiographers may benefit from more training to emotionally support recalled women. While HCPs emphasised taking a patient‐centred communication approach, the use of other strategies (e.g., standardised scripts) and the constraints of the ‘one‐stop shop’ model pose challenges to such an approach. Patient and Public Contribution During the study design, two Patient and Public Involvement members (women with false‐positive‐breast screening test results) were consulted to gain an understanding of patient perspectives and experiences of being recalled specifically in the NHSBSP. Their feedback informed the formulations of the research aim, objectives and the direction of the interview guide.