OBJECTIVE:To use choice-based conjoint survey methodology to evaluate patient values and decision making regarding immediate compared with delayed placement of postpartum intrauterine devices (IUDs). METHODS:We conducted a cross-sectional study in which we surveyed 200 nonpregnant, parous patients. Participants chose between hypothetical postpartum IUDs varying in multiple attributes (hormonal or nonhormonal IUD type, placement timing, 1-year efficacy, expulsion risk, risk of lost strings, and malposition risk). The primary outcome was preference for immediate compared with delayed postpartum IUD placement and importance of placement timing relative to other attributes. Secondarily, we evaluated whether demographic and neighborhood characteristics were associated with timing preference and attribute importance. RESULTS:We included 190 participants for analysis. Most participants (62.6%) preferred delayed placement. There was no significant difference in timing preference by race ( P =.28) or block-level Area Deprivation Index score ( P =.27). Patients who preferred immediate placement were more likely to have public insurance than private insurance (70.4% vs 29.6%, P =.04); however, the majority of patients (55.1%) with public insurance still preferred delayed placement. Attributes of IUD type, malposition risk, 1-year efficacy, and expulsion risk all had greater effects on patient decision making than placement timing. There was no difference in attribute importance by race ( P =.30), Area Deprivation Index score ( P =.88), or insurance type ( P =.22). CONCLUSION:Patients preferred the higher efficacy and lower complication rates of delayed postpartum IUD placement over the convenience of immediate placement. Insurance considerations may affect these timing preferences. There was no difference in attribute importance between demographic groups or based on neighborhood-level factors, indicating that, although both immediate and delayed postpartum IUD placement should be offered, counseling should not vary according to individual demographic characteristics.

Figure S5. Distribution of time to metastasis (TTM) for clinical M0 PDAC patients within our training and test sets. Cross indicates no metastasis observed yet

Figure S1. Sample cohort of this study, which included 204 subjects in total. Workflow shows patient cohorts involved in each classification. * indicated 8 patients repeated in the discovery set and the training set. ** indicated 32 locally advanced patients that were not used in the occult metastases detection as training set did not have locally advanced PDAC patients.

Plasma cell-free DNA (cfDNA) concentration (ng/mL) is correlated with (A), total radiographic tumor burden (contrast-enhancing tumor + T2/FLAIR non-enhancing tumor) and (B), contrast-enhancing tumor burden at the first post-radiation MRI scan in patients with newly diagnosed glioblastoma

Figure S3. Multi-analyte panel generation procedure of PDAC/NC diagnosis and occult metastases detection

Figure S2. miRNA sequencing to discover miRNA biomarkers to discern PDAC from non-cancer. (A) Raw miRNA sequencing data from 6 healthy controls, 6 non-cancer disease controls, 5 M0 PDAC patients, and 12 M1 PDAC patients. (B) 8 potential miRNA candidates were selected using least absolute shrinkage and selection operator (LASSO) for cancer versus non-cancer, achieving AUC=1 within discovery cohort. (C) We selected 5 out of 8 miRNA candidates based on their abundance as detected by qPCR (Cq < 40) and show the average fold changes of these 5 miRNAs between patient groups. (D) We validated these miRNAs by calculating the correlation coefficient between their qPCR data and the miRNA sequencing data. The overall R2 = 0.6

pTMBand PD-L1 expression levels.

Tissue fusion transcript panel gene coverage (55 genes)

Figure S4. Individual biomarker profiles within the training set. 14 biomarkers' levels by patient group within the training set of 47 subjects. Pancreatic cancer patients (PDAC) relative to Non-Cancer patients (NC). Mann-Whitney test was used to evaluate statistical significance. * means P<0.05, ** means P<0.01, **** means P<0.0001.

Overall response to pembrolizumab monotherapy (n=31, left) and combination therapy (n=34*, right).

Circulating tumor DNA next-generation sequencing gene coverage (74 genes)

Equitable access to contraception and contraceptive education has the potential to mitigate health disparities related to unintended pregnancy. Pregnancy and the postpartum window frequently offer reduced insurance barriers to healthcare, increased interaction with healthcare systems and family planning providers, and an opportune time for many individuals to receive contraception; however, there are additional considerations in method type for postpartum individuals, and contraceptive counseling must be thoughtfully conducted to avoid coercion and promote shared decision-making. This commentary reviews method-specific considerations and suggests priorities for achieving equity in postpartum contraceptive access.

BACKGROUND:Medicaid, unlike any other insurance mechanism, imposes a consent requirement on female patients desiring sterilization that must be completed at least 30 days, but no more than 180 days, before sterilization. Desired sterilization cannot be completed in the Medicaid population without this consent. Large-scale national evidence is lacking on the effect of this requirement. OBJECTIVE:This study aimed to explore the influence of insurance status on the achievement of postpartum sterilization after a self-reported unwanted birth in a nationally representative sample. STUDY DESIGN:This was a retrospective cohort analysis using data from the 2013-2015 National Survey of Family Growth. The National Survey of Family Growth uses a stratified, multistage clustered sample to make nationally representative estimates for men and women aged 15 to 44 years in the household population of the United States. The analysis was limited to a cohort of birthing people who reported their last birth as unwanted and who were insured by either Medicaid or private insurance. The survey was analyzed with the application of inverse probability of treatment weights to balance those with Medicaid and those with private insurance in addition to the survey weight. The association between completion of postpartum sterilization and insurance type was evaluated using weighted logistic regression, adjusting for demographic and clinical characteristics. RESULTS:In an adjusted and inverse probability of treatment weight balanced analysis of a weighted national sample representing 4,164,304 people (416 respondents), Medicaid-insured birthing people with history of unwanted births were found to have 56% lower odds of obtaining postpartum sterilization (odds ratio, 0.44; 95% confidence interval, 0.22-0.87; P=.019) than those with private insurance. CONCLUSION:This study adds to mounting evidence that insurance type plays a significant role in the achievement of desired postpartum sterilization, with individuals with Medicaid less likely to undergo the procedure. The findings call for policy reforms around sterilization policy in the United States, emphasizing the need for uniform consent procedures that do not discriminate based on insurance status.

PURPOSE:Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis. Multianalyte signatures, including liquid biopsy and traditional clinical variables, have shown promise for improving prognostication in other solid tumors but have not yet been rigorously assessed for PDAC.MATERIALS AND METHODS:We performed a prospective cohort study of patients with newly diagnosed locally advanced pancreatic cancer (LAPC) or metastatic PDAC (mPDAC) who were planned to undergo systemic therapy. We collected peripheral blood before systemic therapy and assessed circulating tumor cells (CTCs), cell-free DNA concentration (cfDNA), and circulating tumor KRAS (ctKRAS)-variant allele fraction (VAF). Association of variables with overall survival (OS) was assessed in univariate and multivariate survival analysis, and comparisons were made between models containing liquid biopsy variables combined with traditional clinical prognostic variables versus models containing traditional clinical prognostic variables alone.RESULTS:One hundred four patients, 40 with LAPC and 64 with mPDAC, were enrolled. CTCs, cfDNA concentration, and ctKRAS VAF were all significantly higher in patients with mPDAC than patients with LAPC. ctKRAS VAF (cube root; 0.05 unit increments; hazard ratio, 1.11; 95% CI, 1.03 to 1.21; P = .01), and CTCs ≥ 1/mL (hazard ratio, 2.22; 95% CI, 1.34 to 3.69; P = .002) were significantly associated with worse OS in multivariate analysis while cfDNA concentration was not. A model selected by backward selection containing traditional clinical variables plus liquid biopsy variables had better discrimination of OS compared with a model containing traditional clinical variables alone (optimism-corrected Harrell's C-statistic 0.725 v 0.681).CONCLUSION:A multianalyte prognostic signature containing CTCs, ctKRAS, and cfDNA concentration outperformed a model containing traditional clinical variables alone suggesting that CTCs, ctKRAS, and cfDNA provide prognostic information complementary to traditional clinical variables in advanced PDAC.

Purpose: To determine whether a multianalyte liquid biopsy can improve the detection and staging of pancreatic ductal adenocarcinoma (PDAC). Experimental Design: We analyzed plasma from 204 subjects (71 healthy, 44 non-PDAC pancreatic disease, and 89 PDAC) for the following biomarkers: tumor-associated extracellular vesicle miRNA and m RNA isolated on a nanomagnetic platform that we developed and measured by next-generation sequencing or qPCR, circulating cell-free DNA (ccfDNA) concentration measured by qPCR, ccfDNA KRAS G12D/V/R mutations detected by droplet digital PCR, and CA19-9 measured by electrochemiluminescence immunoassay. We applied machine learning to training sets and subsequently evaluated model performance in independent, user-blinded test sets. Results: To identify patients with PDAC versus those without, we generated a classification model using a training set of 47 subjects (20 PDAC and 27 noncancer). When applied to a blinded test set (N = 136), the model achieved an AUC of 0.95 and accuracy of 92%, superior to the best individual biomarker, CA19-9 (89%). We next used a cohort of 20 patients with PDAC to train our model for disease staging and applied it to a blinded test set of 25 patients clinically staged by imaging as metastasis-free, including 9 subsequently determined to have had occult metastasis. Our workflow achieved significantly higher accuracy for disease staging (84%) than imaging alone (accuracy - 64%; P < 0.05). Conclusions: Algorithmically combining blood-based biomarkers may improve PDAC diagnostic accuracy and preoperative identification of nonmetastatic patients best suited for surgery, although larger validation studies are necessary.

Abstract Purpose: The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard-of-care therapy for metastatic non–small cell lung cancer (mNSCLC) has not been explored. Experimental Design: A 500-gene next-generation sequencing panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.gov identifier: NCT03047616). Response was assessed using RECIST 1.1. Associations were made for patient characteristics, 6-month durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS). Results: Of 66 patients, 52 (78.8%) were pTMB-evaluable. Median pTMB was 16.8 mutations per megabase (mut/Mb; range, 1.9–52.5) and was significantly higher for patients achieving DCB compared with no durable benefit (21.3 mut/Mb vs. 12.4 mut/Mb, P = 0.003). For patients with pTMB ≥ 16 mut/Mb, median PFS was 14.1 versus 4.7 months for patients with pTMB < 16 mut/Mb [HR, 0.30 (0.16–0.60); P < 0.001]. Median OS for patients with pTMB ≥ 16 was not reached versus 8.8 months for patients with pTMB < 16 mut/Mb [HR, 0.48 (0.22–1.03); P = 0.061]. Mutations in ERBB2 exon 20, STK11, KEAP1, or PTEN were more common in patients with no DCB. A combination of pTMB ≥ 16 and absence of negative predictor mutations was associated with PFS [HR, 0.24 (0.11–0.49); P < 0.001] and OS [HR, 0.31 (0.13–0.74); P = 0.009]. Conclusions: pTMB ≥ 16 mut/Mb is associated with improved PFS after first-line standard-of-care pembrolizumab-based therapy in mNSCLC. STK11/KEAP1/PTEN and ERBB2 mutations may help identify pTMB-high patients unlikely to respond. These results should be validated in larger prospective studies.

Postmortem CT might provide valuable information in determining the cause of death and understanding disease processes, particularly when combined with traditional autopsy. Pediatric applications of postmortem imaging represent a new and rapidly growing field. We describe our experience in establishing a pediatric postmortem CT program and present a discussion of the distinct challenges in developing this type of program in the United States of America, where forensic practice varies from other countries. We give a brief overview of recent literature along with the common imaging findings on postmortem CT that can simulate antemortem pathology.

The Severity of Alopecia Tool serves as a tool for alopecia research and a clinical guideline for following progression of disease. The original Severity of Alopecia Tool score does not take into account pediatric age groups. As new clinical trials for alopecia areata include more children, a more accurate tool should be available for this population. By collecting images from patients 2-21 years of age and aligning the hair-bearing regions of the scalp, we created an adaptation of the Severity of Alopecia Tool for scoring hair loss percentage of the top, parietal, and occipital scalp in individuals 2-5, 6-11, and 12-21 years of age.

Alopecia areata (AA) is a clinically heterogeneous disease that is characterized by nonscarring hair loss, nail changes, and increased risk of other autoimmune disease. During clinical visits, children with AA often report bullying. We report survey results that highlight the prevalence of bullying and surrounding emotional impact of AA in pediatric patients. We found that bullying was common overall and additional psychological impact, including impairment of social and home life, was even more common. Children of all ages experienced bullying. Boys reported increased physical bullying. Interestingly, those with more severe disease and longer duration of disease experienced less bullying than those with less severe disease.