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Predicting the times of milestone events, ie, interim and final analyses in clinical trials, helps resource planning. This manuscript presents and compares several easily implemented methods for predicting when a milestone event is achieved. We show that it is beneficial to combine the predictions from different models to craft a better predictor through prediction synthesis. Furthermore, a Bayesian approach provides a better measure of the uncertainty involved in prediction of milestone events. We compare the methods through two simulations where the model has been correctly specified and where the models are a mixture of three incorrectly specified model classes. We then apply the methods on two real clinical trial data, North Central Cancer Treatment Group (NCCTG) N0147 and N9841. In summary, the Bayesian prediction synthesis methods automatically perform well even when the data collection is far from homogeneous. AnRshiny app is under development to carry out the prediction in a user‐friendly fashion.

Purpose: To investigate the musculus uvulae morphology in vivo in adults with normal velopharyngeal anatomy and to examine sex and race effects on the muscle morphology. We also sought to provide a preliminary comparison of musculus uvulae morphology in adults with normal velopharyngeal anatomy to adults with repaired cleft palate. Methods: Three-dimensional magnetic resonance imaging data and Amira 5.5 Visualization Modeling software were used to evaluate the musculus uvulae in 70 participants without cleft palate and 6 participants with cleft palate. Muscle length, thickness, width, and volume were compared among participant groups. Results: Analysis of covariance analysis did not yield statistically significant differences in musculus uvulae length, thickness, width, or volume by race or sex among participants without cleft palate when the effect of body size was accounted for. Two-sample t test revealed that the musculus uvulae in participants with repaired cleft palate is significantly shorter ( P = .008, 13.65 mm vs 16.07 mm) and has less volume ( P = .002, 51.08 mm 3 vs 97.62 mm 3 ) than participants without cleft palate. Conclusion: In adults with normal velopharyngeal anatomy, the musculus uvulae is a cylindrical oblong-shaped muscle lying on the nasal surface of the soft palate, with its greatest bulk located just nasal to the levator veli palatini muscle sling. In participants with repaired cleft palate, the musculus uvulae is substantially reduced in volume. This diminished muscle bulk located just at the point where the palate contacts the posterior pharyngeal wall may contribute to velopharyngeal insufficiency in children with repaired cleft palate.

AbstractIn the forensic field, ancestry‐informative markers (AIMs) showing remarkable allele frequency discrepancies can be useful in deducing the likely ancestral origin of a person or estimating the ancestry component proportions of an admixed population or individual. Diallelic single nucleotide polymorphisms are genetic markers commonly used for ancestry inference, but the genotyping methods of single nucleotide polymorphisms fail to fulfil the demands of cost‐effectiveness and simplicity of experimental manipulation. To overcome the limitations, a 39 ancestry‐informative insertion/deletion polymorphism multiplex panel was developed in the present study to perform ancestry assignment of individuals from three distinct biogeographic regions (Africa, Europe, East Asia). And in the panel design, we also attempted to incorporate AIM‐insertion/deletion polymorphisms exhibiting allelic frequency differences in Han, Uyghur, and Tibetan populations into the multiplex assay, further expecting to provide valuable information for refining ancestry inference within Chinese populations. Statistical analyses were performed to estimate efficiency of this panel in clustering individuals from three continents mentioned above into their corresponding populations, which indicated the potential of the panel in ancestry inference. Besides, we also estimated the ancestral component proportions of Uyghur group and STRUCTURE analysis revealed that Uyghurs from Urumchi city of northern Xinjiang exhibited a distinctly admixed pattern of East Asian and European ancestry components with a ratio of 49:44, reflecting the relatively higher East Asian ancestry component contribution in the gene pool of the Uyghur group.

Background: Efforts to improve prescription of oral anticoagulation (OAC) drugs in patients with atrial fibrillation have had limited success in improving guideline adherence. Methods: We evaluated adherence to the American College of Cardiology/American Heart Association performance measures for OAC in eligible patients with a CHA 2 DS 2 -VASc score ≥2 and trends in prescription over time in the American Heart Association’s Get With The Guidelines–AFIB (atrial fibrillation) registry. Adjusted associations with in-hospital outcomes were also determined. The cohort included 33 235 patients with a CHA 2 DS 2 -VASc score ≥2 who were admitted for atrial fibrillation and were enrolled at 115 sites between January 1, 2013, and September 31, 2017. Results: The median (25th, 75th percentile) age was 73 years (65, 81 years); 51% were female; and the median (25th, 75th percentile) CHA 2 DS 2 -VASc score was 4 (3, 5). At admission, 16 206 (59.5%) of 27 221 patients with a previous diagnosis of atrial fibrillation were taking OAC agents, and OAC drug use at admission was associated with a lower adjusted odds of in-hospital ischemic stroke (odds ratio, 0.38; 95% CI, 0.24–0.59; P <0.0001). At discharge, prescription of OAC in eligible patients (no contraindications) was 93.5% (n=25 499 of 27 270). In a sensitivity analysis, when excluding only strict contraindications (4.6%, n=1497 of 32 806), OAC prescription at discharge was 80.3%. OAC prescription at discharge was higher in those aged ≤75 years, men, those with heart failure, those with previous atrial fibrillation ablation, and those with rhythm control ( P <0.0001 for all). OAC use was lowest in Hispanic patients (90.2%, P <0.0001). Prescription of OAC at discharge in eligible patients improved over time from 79.9% to 96.6% ( P <0.0001). Conclusions: Among hospitals participating in the GWTG-AFIB quality improvement program, OAC prescription at discharge in eligible guideline-indicated patients increased significantly and improved consistently over time. These data confirm that high-level adherence to guideline-recommended stroke prevention is achievable.

588 Background: CALGB/SWOG 80405 found no difference in overall survival (OS) or progression-free survival (PFS) in 1137 patients with KRAS wild-type metastatic colorectal cancer (mCRC) treated with either the anti-VEGF agent bevacizumab (Bev) or the anti-EGFR agent cetuximab (Cet) in combination with chemotherapy (FOLFOX or FOLFIRI) as first-line therapy. Additional molecular biomarkers are required for the optimization of treatment choices for patients with mCRC. Methods: Levels of 24 proteins were assayed in EDTA-plasma samples using multiplex ELISA techniques. Plasma samples were collected at baseline and cycle 2 day 1 (C2D1). Analyses of baseline markers have been presented previously. Changes from baseline to C2D1 were expressed as an L-ratio (LR, log2 of C2D1 divided by baseline measure). LRs dichotomized at 0 were analyzed for potential prognostic and predictive effects on OS and PFS using Cox models while adjusting for confounders (post-hoc optimized cutpoints were used for PLGF, TIMP1, VCAM1, and VEGFR3 due to skew in the distributions of these markers). P-values are not corrected for multiple testing. Results: Baseline and matched C2D1 samples from 446 patients (212 Bev/234 Cet) were available for analysis. Thirteen markers were differentially modulated between arms (p < 0.05). Early increases in CD73 (p = 0.001), ICAM1 (p = 0.022), TIMP1 (p = 0.001), TSP2 (p = 0.024), and VEGFR3 (p = 0.006) were prognostic for shorter OS. Increases in ICAM1 (p = 0.008), TIMP1 (p = 0.042), and TGFB1 (p = 0.039) were prognostic for shorter PFS. Changes in VEGFR3 (pint = 0.097) and TGFBR3 (pint = 0.052) were predictive for OS and PFS, respectively. No other markers were predictive for OS or PFS (p < 0.1). Conclusions: Changes in circulating plasma protein biomarkers observed in patients enrolled in CALGB/SWOG 80405 were both prognostic and predictive for OS and PFS and warrant further study. Such changes could provide valuable information and help guide treatment decisions. Support: U10CA180821, U10CA180882, U10CA180888, U10CA180830; ClinicalTrials.gov: NCT00265850. [Table: see text]

AbstractBackground and aimsLittle research has been done on tele‐intensive care unit (ICU) implementation across different types of ICUs, and there exist few studies that have used qualitative research methods to analyze the human and organizational factors influencing optimization of telemedicine for newborn resuscitation. The objective of this study was to understand health care professionals' acceptance, utilization, and integration of video telemedicine for newborn resuscitation (termed teleneonatology) in community hospital settings.MethodsFocus group and individual interviews were conducted with 49 health care professionals at six affiliated health system hospitals. Data were gathered from physicians (n = 18), nurses (n = 30), and a nurse practitioner. Data were inductively analyzed using a thematic approach, and then constructs from normalization process theory (NPT) were deductively applied. NPT rendered a general framework to describe and assess how care teams perceive the implementation of teleneonatology and how they interact with this telemedicine service in their local setting.ResultsLocal health care professionals accepted teleneonatology as an important, helpful service, yet its implementation was perceived as both valuable and a threat to professional traditions. Utilization may depend on perceived benefit, mutual understanding of the guidelines, and expectations of use, and other relational, human, contextual, and system factors. Participants in this study agreed on the need for collective work to successfully integrate teleneonatology into the local practice.DiscussionsNPT uncovered that successful implementation of a teleneonatology program may be facilitated by strong interpersonal relationships among care teams, continuous programmatic training and education, and communicating the clinical value of teleneonatology, including its opportunities and benefits.

Marine omega‐3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon cancer patients who completed a dietary questionnaire at enrollment. Multivariable hazard ratios and 95% confidence intervals (CIs) were calculated for the association between MO3PUFA and disease‐free survival (DFS) and overall survival according toKRASandBRAFV600Emutations and DNA mismatch repair (MMR) status. Higher MO3PUFA intake was associated with improved 3‐year DFS forKRASwild‐type tumors (77%vs. 73%; HR: 0.84; 95% CI: 0.67–1.05) but notKRAS‐mutant tumors (64%vs. 70%; HR: 1.30; 95% CI: 0.97–1.73;Pinteraction= 0.02). Similar heterogeneity was found by MMR (Pinteraction= 0.14): higher MO3PUFA was associated with better 3‐year DFS for tumors with deficient MMR (72%vs. 67%) but not proficient MMR (72%vs. 72%). No heterogeneity was found byBRAFV600Emutation. Similar findings were obtained for overall survival. In conclusion, we found a suggestive beneficial association between higher MO3PUFA intake and improved survival among stage III colon cancer patients with wild‐typeKRASand deficient MMR. Given the relatively small number of cases with tumor molecular assessments, further studies, preferably through pooled analyses of multiples cohorts, are needed to validate our findings.

612 Background: mCRC is a heterogeneous disease leading to possible disparate responses among lesions in a single pt. This study assesses the heterogeneity of lesion responses and evaluates the prognostic value of LBR12 and its mortality risk discrimination beyond RECIST responses. Methods: Pts with ≥ 2 lesions and no new lesions at 12 weeks (wks) were eligible. For each pt, after 12 wks of Rx, each lesion was categorized as progressive disease (L-PD: ≥20% increase in the longest diameter [LD]), partial response (L-PR: ≥30% decrease in LD), or stable disease (L-SD: neither L-PD nor L-PR). LBR12 was defined, per patient, by the combination of lesion responses: homogeneous LBR12 (L-PD, L-SD, L-PR only) and heterogeneous LBR12 (mixture of L-PD/L-SD, L-PD/L-PR, L-SD/L-PR). LBR12 and overall survival (OS) were correlated using stratified multivariate Cox models after adjusting for age, gender, and ECOG PS. Results: Among 9,092 mCRCs (Rx: chemo alone 44%; chemo + VEGF inhibitor [VEGFi] 42%; chemo + EGFR inhibitor [EGFRi] 10%) from 16 1st-line studies. Median OS: 2.2 years. Per RECIST at 12 wks, CR 0%; PR 36.1%; SD 60.9%; PD 3.0%. Responses in 52% were heterogeneous (Table). VEGFi and EGFRi treated pts had the highest rate of L-SD/L-PR (45%) and L-PR only (22%) status, respectively. Median OS increased monotonically across pts with more L-PRs and fewer L-PDs (Table). Pts with L-SD/L-PR status, among which 51% had SD per RECIST, had longer OS than those with L-SD only status (HRadj.= .81, padj.< .0001), but shorter OS than those with L-PR only status (HRadj.= 1.46, padj.< .0001). Pts with L-PD/L-SD status, among which 71% were SD per RECIST, had shorter OS than those with L-SD only status (HRadj.= 2.22, padj.< .0001). These associations were consistent across treatment regimens. Conclusions: The lesion-based response captures the heterogeneity of within pt lesion responses and provides refinement in predicting outcome beyond RECIST response at 12 wks. [Table: see text]