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OBJECTIVES:. Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN:. Multicenter cohort study. SETTING:. ICUs at 68 hospitals across the United States. PATIENTS:. A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

OBJECTIVES:. Critically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019. DESIGN:. This was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration. SETTING:. Sixty-eight U.S. ICUs. PATIENTS:. Adults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model. CONCLUSIONS:. eXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.

Objective Metastatic melanoma patients often receive palliative radiotherapy (RT) and immunotherapy (IT). However, the immunological interplay between RT dose-fractionation and IT is uncertain, and the optimal treatment strategy using RT and IT in metastatic melanoma remains unclear. Our main objective was to examine the effect of RT dose-fractionation on overall survival (OS). Methods Using the National Cancer Database (NCDB), we classified metastatic melanoma patients who received palliative RT into two dose-fractionation groups - conventionally fractionated RT (CFRT; <5 Gy/fraction) and hypofractionated RT (HFRT: ≥5 Gy/fraction) - with or without IT. Survival analysis was performed using the Cox regression model, Kaplan-Meier method, and propensity-score matching (PSM). Results A total of 5,281 metastatic melanoma patients were included, with a median follow-up of 5.9 months. The three-year OS was highest in patients who received HFRT+IT [37.3% (95% CI: 31.1-43.5)] compared to those who received HFRT alone [19.0% (95% CI: 16.2-21.9)], CFRT+IT [17.6 (95%CI: 13.9-21.6)], or CFRT alone [8.6% (95%CI: 7.6-9.7); p<0.0001]. The magnitude of OS benefit with the use of IT was greater in those who received HFRT (18.3%) compared with those who received CFRT (9.0%) (p<0.0001). The addition of IT to HFRT, compared to CFRT, was associated with greater OS benefit in patients treated with RT to the brain and soft tissue/visceral (STV) sites. On PSM analysis, HFRT+IT was associated with improved three-year OS compared to other treatments. Conclusion Metastatic melanoma patients who received HFRT+IT was associated with the greatest OS benefit. Our findings warrant further prospective evaluation as to whether higher RT dose-per-fraction improves clinical outcomes in metastatic melanoma patients receiving IT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Wang et al.)

Purpose: The literature has been conflicting on the superiority of adjuvant chemoradiation over chemotherapy for node-positive adenocarcinoma of the pancreas following definitive surgery. We aimed to evaluate the patterns of care and outcomes of these two treatment options using the National Cancer Database (NCDB)., Methods: Patients diagnosed with non-metastatic, node-positive adenocarcinoma of the pancreas from 2006 to 2014 who received oncologic resection with negative margins were identified in the NCDB. Patient- and clinical-related factors were compared between those who received adjuvant chemotherapy alone (aC) versus adjuvant chemoradiation (aCRT). Univariable and multivariable logistic regression was performed to assess for predictors of adjuvant chemoradiation use. The Kaplan-Meier method was used to assess overall survival (OS) and Cox regression analysis was used to assess impact of covariables on OS., Results: There were 3609 patients who met the study criteria, of which 2988 (82.8%) received chemotherapy alone and 621 (17.2%) who received chemoradiation. Median follow up for living patients was 33.8 months (IQR 22-51). On multivariable logistic regression, those who received treatment in more recent years of diagnoses (OR 0.21-0.37, p < 0.001) were less likely to receive aCRT over aC. Two-year OS for those who received chemo alone was 44.9% and for chemoradiation was 42.6% (p = 0.169). This finding was sustained on multivariable survival analysis (HR 0.99, p = 0.867)., Conclusions: Adjuvant chemotherapy alone for adenocarcinoma of the pancreas is the predominant treatment of choice among US hospitals. There was no overall survival benefit noted in those who were treated with adjuvant chemoradiation.

Background: Little is known about the readability and utility of patient education materials for stereotactic radiosurgery (SRS). Therefore, the goal of this investigation was to evaluate such materials from high-performing neurosurgery hospitals and professional societies through an analysis of readability and educational content., Methods: In this cross-cross sectional study, 61 websites associated with the top 50 neurosurgery and neurology hospitals according to U.S. News & World Report (USNWR) and 11 predetermined professional medical societies were queried. Identified SRS education materials were analyzed by 6 readability indices. Educational content was assessed by 10 criteria based on surveys of patients' perspectives about SRS., Results: Fifty-four materials were identified from the target population (45 from USNWR hospital websites and 9 from professional society websites). Mean readability of materials ranged from 11.7 to 15.3 grade level, far more difficult than national recommendations of sixth and eighth grade. Materials were found to have deficiencies in educational content. Compared with high-performing hospitals, materials from websites of professional societies were longer ( P = .002), and more likely to discuss risks and benefits specific to SRS ( P = .008), alternative treatment options ( P = .05) and expected outcomes or postprocedure descriptions ( P = .004). Hospital materials were also more likely to favor brand-specific terminology (eg, GammaKnife) over generic terminology (eg, radiosurgery; P = .019)., Conclusion: Publicly available online patient educational materials for SRS are written at reading levels above national recommendations. Furthermore, many lack information identified as important by patients. Reevaluation and improvement of online SRS educational materials on a national scale are warranted., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Strong mentorship has been shown to improve mentee productivity, clinical skills, medical knowledge, and career preparation. We conducted a survey to evaluate resident satisfaction with mentorship within their radiation oncology residency programs. Methods and Materials: In January 2019, 126 radiation oncology residents training at programs in the northeastern United States were asked to anonymously complete the validated Munich Evaluation of Mentoring Questionnaire (MEMeQ). Results of residents with a formal mentoring program were compared to those without a formal program. Results: Overall response rate was 42%( n = 53). Participants were 25% post-graduate year two (PGY-2), 21% PGY-3, 26% PGY-4, and 28% PGY-5. Only 38% of residents reported participation in a formal mentoring program, while 62% had no formal program, and 13% reported having no mentor at all. Residents participating in a formal mentoring program reported strikingly higher rates of overall satisfaction with mentoring compared to those who were not (90% vs. 9%, p < 0.001). Overall, 38% of residents were either satisfied/very satisfied with their mentoring experience, while 49% of residents were unsatisfied/very unsatisfied. Conclusion: Residents participating in a formal mentorship program are significantly more likely to be satisfied with their mentoring experience than those who are not. Our results suggest that radiation oncology residency programs should strongly consider implementing formal mentorship programs., (Copyright © 2019 Sayan, Ohri, Lee, Abou Yehia, Gupta, Byun, Jabbour, Wagman, Haffty, Weiner and Kim.)

Purpose: Prior research suggests that patient education materials on radiation therapy from various professional groups are written at reading levels above national recommendations of sixth to eighth grade. Since publication of these initial findings, many materials from these sources have been updated or newly created. However, the extent to which readability was considered in the design of these new documents remains unknown. Therefore, the goal of this investigation was to evaluate readability of online education materials for radiation therapy, comparing readability of updated materials with those included in the previous study., Methods and Materials: Patient education materials related to radiation oncology were identified from websites of the 3 professional societies used in the original investigation (the American College of Radiology, the American Cancer Society, and the American Society for Radiation Oncology). The documents included in the first analysis were used as a comparator. To allow for accurate evaluation across groups, materials were matched by content; when necessary, documents were combined from the original cohort to create topically equivalent materials to reflect those currently available on society websites. Identified materials were analyzed using 7 validated readability indices, and results are reported in grade-level equivalents. Original materials were also reanalyzed with the same method., Results: American Cancer Society materials had the lowest average baseline levels (9.4-11.3 grade level) and showed improved readability in the more recent materials (8.0-10.5 grade level). By contrast, the American Society for Radiation Oncology materials had high average baseline readability levels (11.1-13.9 grade level) that actually worsened in the more recent materials (11.7-16.2 grade level). The number of documents meeting national recommendations did not improve in the updated cohort., Conclusion: Despite evidence that readability levels of patient education materials in radiation oncology are unacceptably high, the readability of newly created materials is not consistently improving across professional societies. Although certain groups may incorporate readability in the design of educational documents, more consistent consideration across all organizations is needed., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: The role of local therapy, in the form of radiation therapy (RT) or radical prostatectomy(RP), and its association on outcomes is not well established in patients with metastatic prostate cancer., Methods: Using the National Cancer Database (NCDB), we evaluated patterns of care and outcomes among patients diagnosed with metastatic prostate cancer from 2004 to 2013 treated with local therapy (RP, intensity-modulated radiation therapy [IMRT], or 2D/3D-conformal radiation therapy [CRT]). The association between local therapy, co-variates, and outcomes was assessed in a multivariable Cox proportional hazards model and Propensity score (PS) matching was performed to balance confounding factors. Survival was estimated using the Kaplan-Meier method., Results: Among the 1,208,180 patients in the NCDB with prostate cancer, 6,051 patients met the inclusion criteria. No local therapy was used in 5,224 patients, while 622 (10.3%), 52 (0.9%), 153 (2.5%) patients received RP, IMRT, and 2D/3D-CRT, respectively. Use of local therapy was associated with younger age (≤70), lower co-morbidity score, lower T-stage, Gleason score <8, node-negative status, private, and Medicare insurance, higher income quartile, and treatment at comprehensive or academic/research programs (P < 0.05). Five-year overall survival for patients receiving local therapy was 45.7% versus 17.1% for those not receiving local therapy (P < 0.01). In multivariate analysis, RP (HR = 0.51; 95%CI, 0.45-0.59, P < 0.01) and IMRT (HR = 0.47; 95%CI, 0.31-0.72, P < 0.01) were independently associated with superior overall survival. After PS-matching, the use of local therapy (RP or IMRT) remained significantly associated with overall survival (HR = 0.35; 95%CI, 0.30-0.41, P < 0.01)., Conclusions: The use of RP and IMRT, to treat the primary disease, was associated with improvements in overall survival for patients with metastatic prostate cancer. We have identified patient-specific variations in the use of local therapy that may be tested in subsequent prospective clinical trials to improve patient outcomes in this setting. Prostate 77: 559-572, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Purpose: Precise patient positioning is critical due to the large fractional doses and small treatment margins employed for thoracic stereotactic body radiation therapy (SBRT). The goals of this study were to evaluate the following: (1) the accuracy of kilovoltage x-ray (kV x-ray) matching to bony anatomy for pretreatment positioning; (2) the magnitude of intrafraction tumor motion; and (3) whether treatment or patient characteristics correlate with intrafraction motion., Methods and Materials: Eighty-seven patients with lung cancer were treated with SBRT. Patients were positioned with orthogonal kV x-rays matched to bony anatomy followed by cone-beam computed tomography (CBCT), with matching of the CBCT-visualized tumor to the internal gross target volume obtained from a 4-dimensional CT simulation data set. Patients underwent a posttreatment CBCT to assess the magnitude of intrafraction motion., Results: The mean CBCT-based shifts after initial patient positioning using kV x-rays were 2.2 mm in the vertical axis, 1.8 mm in the longitudinal axis, and 1.6 mm in the lateral axis (n = 335). The percentage of shifts greater than 3 mm and 5 mm represented 39% and 17%, respectively, of all fractions delivered. The mean CBCT-based shifts after treatment were 1.6 mm vertically, 1.5 mm longitudinally, and 1.1 mm laterally (n = 343). Twenty-seven percent and 10% of shifts were greater than 3 mm and 5 mm, respectively. Univariate and multivariable analysis demonstrated a significant association between intrafraction motion with weight and pulmonary function., Conclusions: Kilovoltage x-ray matching to bony anatomy is inadequate for accurate positioning when a conventional 3-5 mm margin is employed prior to lung SBRT. Given the treatment techniques used in this study, CBCT image guidance with a 5-mm planning target volume margin is recommended. Further work is required to find determinants of interfraction and intrafraction motion that may help guide the individualized application of planning target volume margins., (Copyright © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the relationship between maternal opioid agonists, methadone, or buprenorphine (BPH), and concurrent psychiatric medication use on length of hospitalization (LOS) among infants with neonatal abstinence syndrome (NAS)., Methods: We reviewed the charts of infants born at Boston Medical Center between 2003 and 2009 with a diagnosis of NAS whose mothers were prescribed methadone or BPH for opiate addiction. Univariate and multivariate linear regression analyses were used to examine associations between maternal opioid substitution concurrent with psychiatric medication use and infant LOS. We also tested whether exposure to BPH was associated with a shorter hospitalization., Results: A total of 273 mother-infant pairs were identified. The average LOS for all infants was 22.9 days (SD: 10.9). In bivariate analyses, maternal use of any psychiatric medication was associated with a longer infant LOS (P < 0.005). Compared with those prescribed methadone alone (n = 158), those also taking benzodiazepines (n = 56) had a 5.88-day longer LOS (95% confidence interval [CI]: 2.15-9.60, P = 0.002). Infants of mothers taking methadone plus an selective serotonin re-uptake inhibitor (n = 51) had a longer LOS (β = 4.47, 95% CI: 1.15-7.79) compared to methadone alone; results remained significant in an initial multivariate model, however the effect was attenuated when additional psychiatric medication use was added to the model. Compared with those exposed to methadone, those exposed to BPH (n = 22) had a significantly shorter LOS (ß = -7.35, CI: -0.18 to -14.52, P = 0.04)., Conclusions: Maternal use of prescribed methadone and benzodiazepines, compared to methadone alone, increased LOS for infants with NAS by 6 days. Maternal use of BPH was associated with a shorter LOS.

Background: Woman who struggle with drug addiction during pregnancy are perhaps the most vulnerable of new mothers. The opioid substitution medications methadone and buprenorphine are both compatible with breastfeeding. The objective of this study is to determine breastfeeding rates among opioid-dependent women giving birth in a Baby-Friendly Hospital., Methods: We performed a retrospective chart review of all infants born at Boston Medical Center (Boston, MA) between July 2003 and January 2009 with a diagnosis of neonatal abstinence syndrome. Feeding information was obtained, as well as baseline medical information about the mother-infant pairs. Breastfeeding eligibility was determined by a negative urine toxicology screen on admission, no illicit drug use in the third trimester, and a negative human immunodeficiency virus status., Results: Two hundred seventy-six mother-infant pairs were identified. Forty percent of the mothers carried one or more psychiatric diagnoses; 24% were taking two or more psychiatric medications. Sixty-eight percent of the mothers were eligible to breastfeed; of those, 24% breastfed to some extent during their infant's hospitalization. Sixty-percent of those who initiated stopped breastfeeding after an average of 5.88 days (SD 6.51)., Conclusions: Breastfeeding rates among opioid-dependent women were low, with three-quarters of those eligible electing not to breastfeed. Of the minority of women who did choose to breastfeed, more than half stopped within 1 week.