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Improving academic outcomes for economically disadvantaged students has proven challenging, particularly for children at older ages. We present two large-scale randomized controlled trials of a high-dosage tutoring program delivered to secondary school students in Chicago. One innovation is to use paraprofessional tutors to hold down cost, thereby increasing scalability. Participating in math tutoring increases math test scores by 0.18 to 0.40 standard deviations, and increases math and nonmath course grades. These effects persist into future years. The data are consistent with increased personalization of instruction as a mechanism. The benefit-cost ratio is comparable to many successful early childhood programs. (JEL H75, I21, I24, I26, I32, J13, J15)

In this paper we seek to understand the relationship between the online popularity of an article and its intrinsic quality. Prior experimental work suggests that the relationship between quality and popularity can be very distorted due to factors like social influence bias and inequality in visibility. We conduct a study of popularity on two different social news aggregators, Reddit and Hacker News. We define quality as the number of votes an article would have received if each article was shown, in a bias-free way, to an equal number of users. We propose a simple Poisson regression method to estimate this quality metric from time-series voting data. We validate our methods on data from Reddit and Hacker News, as well the experimental data from prior work. Using these estimates, we find that popularity on Reddit and Hacker News is a relatively strong reflection of intrinsic quality.

Objectives The influence of older age at diagnosis in combination with race/ethnicity on utilization and results of the 21-gene recurrence score (RS) assay for breast cancer (BC) patients is not fully understood. Our objectives were to evaluate the utilization of RS among older women with BC, the likelihood of a high-risk RS, and factors associated with breast cancer-specific mortality (BCSM) among older patients across different races. Materials and methods We utilized the Surveillance, Epidemiology, and Results (SEER) database with linked RS results to evaluate women with estrogen receptor-positive BC diagnosed 2004–2015. Multivariable logistic regression was used to describe the differences in utilization of RS testing and the association of high-risk RS according to patient characteristics. The Cox proportional hazards model was used to analyze factors associated with BCSM. Results We found that 20.4% (109,244/536,555) of all women ≥18 and 14.3% (33,584/235,171) of women ≥65 underwent RS testing. Non-whites had lower odds of RS testing at younger ages whereas among women ≥65 there was no significant difference. After taking into account stage and grade, being ≥65 reduced the odds of high-risk RS in all races except American Indian/Alaskan Native. Age ≥ 65 was independently associated with increased hazard BCSM. Among women ≥65 with high-risk RS, chemotherapy was associated with lower hazard of BCSM in all races. Conclusions Older women are less likely to be tested for RS, but also less likely to have high-risk RS. Older women with high-risk RS, when given chemotherapy have reduced BCSM across all races.

OBJECTIVEEndovascular thrombectomy (EVT) and tissue plasminogen activator (tPA) are effective ischemic stroke treatments in the initial treatment window. In the extended treatment window, these treatments may offer benefit, but CT and MR perfusion may be necessary to determine patient eligibility. Many hospitals do not have access to advanced imaging tools or EVT capability, and further patient care would require transfer to a facility with these capabilities. To assist transfer decisions, the authors developed risk indices that could identify patients eligible for extended-window EVT or tPA.METHODSThe authors retrospectively identified stroke patients who had concurrent CTA and perfusion and evaluated three potential outcomes that would suggest a benefit from patient transfer. The first outcome was large-vessel occlusion (LVO) and target mismatch (TM) in patients 5–23 hours from last known normal (LKN). The second outcome was TM in patients 5–15 hours from LKN with known LVO. The third outcome was TM in patients 4.5–12 hours from LKN. The authors created multivariable models using backward stepping with an α-error criterion of 0.05 and assessed them using C statistics.RESULTSThe final predictors included the National Institutes of Health Stroke Scale (NIHSS), the Alberta Stroke Program Early CT Score (ASPECTS), and age. The prediction of the first outcome had a C statistic of 0.71 (n = 145), the second outcome had a C statistic of 0.85 (n = 56), and the third outcome had a C statistic of 0.86 (n = 54). With 1 point given for each predictor at different cutoffs, a score of 3 points had probabilities of true positive of 80%, 90%, and 94% for the first, second, and third outcomes, respectively.CONCLUSIONSDespite the limited sample size, compared with perfusion-based examinations, the clinical variables identified in this study accurately predicted which stroke patients would have salvageable penumbra (C statistic 71%–86%) in a range of clinical scenarios and treatment cutoffs. This prediction improved (C statistic 85%–86%) when utilized in patients with confirmed LVO or a less stringent tissue mismatch (TM < 1.2) cutoff. Larger patient registries should be used to validate and improve the predictive ability of these models.

BACKGROUND: Hospitals are increasingly adopting ward-based high-flow nasal cannula (HFNC) protocols that allow HFNC treatment of bronchiolitis outside of the intensive care unit (ICU). Our objective was to determine whether adoption of a ward-based HFNC protocol reduces ICU utilization. METHODS: We examined a retrospective cohort of infants aged 3 to 24 months hospitalized with bronchiolitis at hospitals in the Pediatric Health Information System database. The study exposure was adoption of a ward-based HFNC protocol, measured by direct contact with pediatric hospital medicine leaders at each hospital. All analyses utilized an interrupted time series approach. The primary analysis compared outcomes three respiratory seasons before and three respiratory seasons after HFNC adoption, among adopting hospitals. Supplementary analysis 1 mirrored the primary analysis with the exception that the first season after adoption was censored. In supplementary analysis 2, effects among nonadopting hospitals were subtracted from effects measured among adopting hospitals. RESULTS: Of 44 contacted hospitals, 41 replied (93% response rate), of which 18 were categorized as non-adopting hospitals and 12 were categorized as adopting hospitals. Included ward-based HFNC protocols were adopted between the 2010-2011 and 2015-2016 respiratory seasons. The primary analysis included 26,253 bronchiolitis encounters and measured immediate increases in the proportion of patients admitted to the ICU (absolute difference, 3.1%; 95% CI, 2.8%-3.4%) and ICU length of stay (absolute difference, 9.1 days per 100 patients; 95% CI, 5.1-13.2). Both supplementary analyses yielded similar findings. CONCLUSION: Early protocols for ward-based HFNC were paradoxically associated with increased ICU utilization.

Clinicians from different care settings can distort the problem list from conveying a patient’s actual health status, affecting quality and patient safety. To measure this effect, a reference standard was built to derive a problem-list based model. Real-world problem lists were used to derive an ideal categorization cutoff score. The model was tested against patient records to categorize problem lists as either having longitudinal inconsistencies or not. The model was able to successfully categorize these events with ~87% accuracy, ~83% sensitivity, and ~89% specificity. This new model can be used to quantify intervention effects, can be reported in problem list studies, and can be used to measure problem list changes based on policy, workflow, or system changes.

BACKGROUND: Bronchiolitis is often described to follow an expected clinical trajectory, with a peak in severity between days 3 and 5. This predicted trajectory may influence anticipatory guidance and clinical decision-making. We aimed to determine the association between day of illness at admission and outcomes, including hospital length of stay, receipt of positive-pressure ventilation, and total cough duration. METHODS: We compiled data from 2 multicenter prospective studies involving bronchiolitis hospitalizations in patients RESULTS: The median (interquartile range) day of illness at admission for 746 patients was 4 (2–5) days. Day of illness at admission was not associated with length of stay (coefficient 0.01 days, 95% confidence interval [CI]: −0.05 to 0.08 days), positive-pressure ventilation (adjusted odds ratio: 1.0, 95% CI: 0.9 to 1.1), or total cough duration (coefficient 0.33 days, 95% CI: −0.01 to 0.67 days). Additionally, there was no significant difference in day of illness at discharge in readmitted versus nonreadmitted patients (5.9 vs 6.4 days, P = .54). The median cough duration postdischarge was 6 days, with 65 (14.3%) patients experiencing cough for 14+ days. CONCLUSIONS: We found no associations between day of illness at admission and outcomes in bronchiolitis hospitalizations. Practitioners should exercise caution when making clinical decisions or providing anticipatory guidance based on symptom duration.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a known risk factor for ischemic stroke though angiographic imaging is often negative. Our goal was to determine the relationship between vessel wall enhancement (VWE) in acute and future ischemic stroke in CAA patients. MATERIALS AND METHODS: This was a retrospective study of patients with new-onset neurologic symptoms undergoing 3T vessel wall MR imaging from 2015 to 2019. Vessel wall enhancement was detected on pre- and postcontrast flow-suppressed 3D T1WI. Interrater agreement was evaluated in cerebral amyloid angiopathy–positive and age-matched negative participants using a prevalence- and bias-adjusted kappa analysis. In patients with cerebral amyloid angiopathy, multivariable Poisson and Cox regression were used to determine the association of vessel wall enhancement with acute and future ischemic stroke, respectively, using backward elimination of confounders to P < .20. RESULTS: Fifty patients with cerebral amyloid angiopathy underwent vessel wall MR imaging, including 35/50 (70.0%) with ischemic stroke and 29/50 (58.0%) with vessel wall enhancement. Prevalence- and bias-corrected kappa was 0.82 (95% CI, 0.71–0.93). The final regression model for acute ischemic stroke included vessel wall enhancement (prevalence ratio = 1.5; 95% CI, 1.1–2.2; P = .022), age (prevalence ratio = 1.02; 95% CI, 1.0–1.05; P = .036), time between symptoms and MR imaging (prevalence ratio = 0.9; 95% CI, 0.8–0.9; P < .001), and smoking (prevalence ratio = 0.7; 95% CI, 0.5–1.0; P = .042) with c-statistic = 0.92 (95% CI, 0.84–0.99). Future ischemic stroke incidence with cerebral amyloid angiopathy was 49.7% (95% CI, 34.5%–67.2%) per year over a total time at risk of 37.5 person-years. Vessel wall enhancement–positive patients with cerebral amyloid angiopathy demonstrated significantly shorter stroke-free survival with 63.9% (95% CI, 43.2%–84.0%) versus 32.2% (95% CI, 14.4%–62.3%) ischemic strokes per year, chi-square = 4.9, P = .027. The final model for future ischemic stroke had a c-statistic of 0.70 and included initial ischemic stroke (hazard ratio = 3.4; 95% CI, 1.0–12.0; P = .053) and vessel wall enhancement (hazard ratio = 2.5; 95% CI, 0.9–7.0; P = .080). CONCLUSIONS: Vessel wall enhancement is associated with both acute and future stroke in patients with cerebral amyloid angiopathy.

PURPOSE: To identify factors predictive of having supernumerary embryos in a fresh IVF cycle and create a prediction model for clinical counseling. METHODS: We utilized a multivariable Poisson regression to identify predictive factors and then entered these into a logistic regression model, calculating a risk index for each significant variable. The final model was tested using a receiver operating characteristic curve. RESULTS: A total of 60,616 fresh transfer cycles were reported to the Society for Assisted Reproductive Technology in 2014. Of these, 47.17% produced supernumerary embryos. A multivariate Poisson regression identified factors predictive of having supernumerary embryos, with age and AMH being the most predictive. Clinical prediction models were developed with acceptable and excellent discrimination. 23.5% of our cohort did not achieve a live birth following their fresh transfer and had excess embryos cryopreserved for future attempts. CONCLUSION: Our study suggests that in a minority of fresh IVF cycles in the USA, the fresh transfer is not successful, and there are excess embryos cryopreserved for future use. The likelihood of excess embryos beyond those that would be transferred can be predicted with satisfactory precision prior to initiation of the cycle and with improved precision after fresh embryo transfer. Providing patients with a realistic estimate of their chances of having excess embryos at an initial IVF consult especially those with suspected poor prognosis can be beneficial in determining whether to proceed with multiple embryo banking cycles as opposed to proceeding with a fresh transfer, and whether to opt for an enhanced embryo selection technique such as preimplantation genetic testing for aneuploidy (PGT-A). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-020-01731-8) contains supplementary material, which is available to authorized users.

Introduction: Although prior studies have examined the later-life risk of stroke in women with a history of preeclampsia, they have relied on claims data or epidemiological studies with poorly detailed risk factor or outcome data. The Framingham Heart Study (FHS) is a landmark epidemiological study that began in 1948 and followed participants aged 30-59 at baseline until death. The study enrolled 5,209 residents of Framingham, Massachusetts, almost half of which were female. The adjudicated outcome of stroke was ascertained during follow-up visits until 2015, death, or loss to follow-up. Methods: We examined a cohort of 2,136 women from FHS for an association of preeclampsia with stroke occurrence. With each subject having their own unique history of exposures and treatments that vary over time, standard approaches of adjusting for confounding are biased when time-dependent confounders exist. Using a marginal structural model, the effects of possible time-dependent confounders were controlled for using inverse-probability-of-treatment weighted estimators. At each of the study visits, potential confounders were evaluated. Variables controlled for, across the study visits, included age, blood pressure, cholesterol, weight, glucose, treatment for hypertension, treatment for hyperlipidemia, and smoking. Results: Two hundred women (9.4%) had preeclampsia and 380 women (17.8%) had strokes. As compared with the 1,936 women who did not have a history with preeclampsia, the 200 women with a history of preeclampsia had a significantly higher risk of stroke (adjusted Hazard Ratio, 2.29; 95% CI, 1.13 - 4.63) when controlling for time-dependent confounders. Conclusion: A history of preeclampsia is associated with a significantly increased risk of a future stroke. Prior approaches to analyses of this nature have not fully emphasized the importance of controlling for time-dependent confounders with methods such as marginal structural modeling. We plan on analyzing the mediators of the observed association to determine which risk factors might prove beneficial for disease-modifying treatment in midlife.

To determine whether intraoperative measures of right ventricular (RV) function using transesophageal echocardiography are associated with subsequent RV failure after left ventricular assist device (LVAD) implantation.Retrospective, nonrandomized, observational study.Single tertiary-level, university-affiliated hospital.The study comprised 100 patients with systolic heart failure undergoing elective LVAD implantation.Transesophageal echocardiographic images before and after cardiopulmonary bypass were analyzed to quantify RV function using tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (S'), fractional area change (FAC), RV global longitudinal strain, and RV free wall strain. A chart review was performed to determine which patients subsequently developed RV failure (right ventricular assist device placement or prolonged inotrope requirement ≥14 days).Nineteen patients (19%) subsequently developed RV failure. Postbypass FAC was the only measure of RV function that distinguished between the RV failure and non-RV failure groups (21.2% v 26.5%; p = 0.04). The sensitivity, specificity, and area under the curve of an abnormal RV FAC (35%) for RV failure after LVAD implantation were 84%, 20%, and 0.52, respectively. No other intraoperative measure of RV function was associated with subsequent RV failure. RV failure increased ventilator time, intensive care unit and hospital length of stay, and mortality.Intraoperative measures of RV function such as tricuspid annular plane systolic excursion, tricuspid annular systolic velocity, and RV strain were not associated with RV failure after LVAD implantation. Decreased postbypass FAC was significantly associated with RV failure but showed poor discrimination.

Purpose Although several feasibility studies have demonstrated the safety of adjuvant concurrent chemoradiotherapy (CRT) for locally advanced or incompletely resected non–small-cell lung cancer (NSCLC), it remains uncertain whether this approach is superior to sequential chemotherapy followed by postoperative radiotherapy (C→PORT). We sought to determine the most effective treatment sequence. Patients and Methods Using the National Cancer Database, we selected two cohorts of patients with nonmetastatic NSCLC who had received at least a lobectomy followed by multiagent chemotherapy and radiotherapy; cohort one included patients with R0 resection and pN2 disease, whereas cohort two included patients with R1-2 resection regardless of nodal status. Overall survival (OS) was examined using a propensity score–matched analysis with a shared frailty Cox regression. Results A total of 747 patients in cohort one and 277 patients in cohort two were included, with a median follow-up of 32.8 and 27.9 months, respectively. The median OS was 58.8 months for patients who received C→PORT versus 40.4 months for patients who received CRT in cohort one (log-rank P < .001). For cohort two, the median OS was 42.6 months for patients who received C→PORT versus 38.5 months for patients who received CRT (log-rank P = .42). After propensity score matching, C→PORT remained associated with improved OS compared with CRT in cohort one (hazard ratio, 1.35; P = .019), and there was no statistical difference in OS between the sequencing groups for cohort two (hazard ratio, 1.35; P = .19). Conclusion Patients with NSCLC who undergo R0 resection and are found to have pN2 disease have improved outcomes when adjuvant chemotherapy is administered before, rather than concurrently with, radiotherapy. For patients with positive margins after surgery, there is not a clear association between treatment sequencing and survival.

Purpose Esophageal stenting is often considered to relieve dysphagia in patients with locoregionally advanced esophageal cancer. We sought to determine the effects of stenting on the incidence of acute toxicity and oncologic outcomes in patients undergoing chemoradiation therapy (CRT). Methods and Materials The data from patients treated with curative intent CRT for locoregionally advanced esophageal cancer at the University of Utah were retrospectively analyzed. The χ2 or Fisher exact test was used to compare the demographic and tumor characteristics between patients with and without esophageal stenting before RT. Univariate and multivariate analyses using logistic regression modeling were used to identify the predictors of acute toxicities. A propensity score–matched analysis with shared frailty Cox hazard regression was performed according to stent status to identify the stent effect on survival. Acute toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4. Results From 2005 to 2013, 103 consecutive patients received CRT. Of the 103 patients, 28 had a stent in place during CRT. The median dose was 50.4 Gy for all patients. Grade ≥3 acute toxicities were seen in 71% of the stent versus 27% of the no-stent patients (P Conclusions In patients undergoing CRT with curative intent, esophageal stenting was associated with significantly increased grade ≥3 acute toxicities, fewer patients proceeding to esophagectomy, and worse overall survival.

To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer.The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log-rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score-matched analysis was also conducted among women with cervical involvement.We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log-rank P.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score-matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01).In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

We study social comparisons and status seeking in an interconnected society. Individuals take costly actions that have direct benefits and also confer social status. A new measure of interconnectedness—cohesion—captures the intensity of incentives for seeking status. Equilibria stratify players into social classes, with each class’s action pinned down by cohesion. A network decomposition algorithm characterizes the highest (and most inefficient) equilibrium. Members of the largest maximally cohesive set form the highest class. Alternatively, players not belonging to sets more cohesive than the set of all nodes constitute the lowest class. Intermediate classes are identified by iterating a cohesion operator. We also characterize networks that accommodate multiple-class equilibria. (JEL D11, D85, Z13)

This study evaluates the association of adding questions about gun storage in patient households in the electronic health record with documentation of gun storage in the context of mass shootings.

BACKGROUND AND OBJECTIVES: An early-onset sepsis (EOS) risk calculator tool to guide evaluation and treatment of infants at risk for sepsis has reduced antibiotic use without increased adverse outcomes. We performed an electronic health record (EHR)–driven quality improvement intervention to increase calculator use for infants admitted to a newborn nursery and reduce antibiotic treatment of infants at low risk for sepsis. METHODS: This 2-phase intervention included programming (1) an EHR form containing calculator fields that were external to the infant’s admission note, with nonautomatic access to the calculator, education for end-users, and reviewing risk scores in structured bedside rounds and (2) discrete data entry elements into the EHR admission form with a hyperlink to the calculator Web site. We used statistical process control to assess weekly entry of risk scores and antibiotic orders and interrupted time series to assess trend of antibiotic orders. RESULTS: During phase 1 (duration, 14 months), a mean 59% of infants had EOS calculator scores entered. There was wide variability around the mean, with frequent crossing of weekly means beyond the 3σ control lines, indicating special-cause variation. During phase 2 (duration, 2 years), mean frequency of EOS calculator use increased to 85% of infants, and variability around the mean was within the 3σ control lines. The frequency of antibiotic orders decreased from preintervention (7%) to the final 6 months of phase 2 (1%, P < .001). CONCLUSIONS: An EHR-driven quality improvement intervention increased EOS calculator use and reduced antibiotic orders, with no increase in adverse events.

Introduction: Hypertension is the leading cause of small-vessel stroke; however, mechanisms of stroke related to blood pressure variability (BPV) are not well understood. Hypothesis: Greater BPV will be correlated with increased ischemic stroke recurrence in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. Methods: All blood pressures in the 30 days after randomization were excluded to reduce confounding from the study intervention. The study exposure was BPV, defined as standard deviation (SD) and coefficient of variation of the systolic blood pressure, during days 30-365 of SPS3. Cox proportional hazards regression was used to calculate hazard ratios relating BPV to stroke events during the remainder of study follow-up. Patients were excluded if they had stroke during the exposure period. Results: This analysis included 2,764 patients, 157 (5.7%) of whom developed stroke. Mean±SD follow-up was 1091±699 days and number of blood pressure readings per patient was 39±14. The SD was higher in patients who developed recurrent stroke (Table 1). A 10 mm Hg shift in SD was associated with a hazard ratio of 1.53 for stroke (Table 2). This association was not affected by SPS3 blood pressure treatment arm. Conclusion: Greater BPV was associated with a minor increase in the risk of recurrent stroke in SPS3. Additional research is needed to understand the causal mechanism and methods to reduce BPV.

BACKGROUND AND PURPOSE: MR imaging–detected carotid intraplaque hemorrhage indicates vulnerable plaque with high stroke risk. Angiotensin II stimulates intraplaque hemorrhage in animal models, and the angiotensin system is highly regulated by vitamin D. Our purpose was to determine whether low vitamin D levels predict carotid intraplaque hemorrhage in humans. MATERIALS AND METHODS: In this cross-sectional study, 65 patients with carotid disease underwent carotid MR imaging and blood draw. Systemic clinical confounders and local lumen imaging markers were recorded. To determine the association of low vitamin D levels with MR imaging detected intraplaque hemorrhage, we performed multivariable Poisson regression by using generalized estimating equations to account for up to 2 carotid arteries per patient and backward elimination of confounders. MR imaging detected intraplaque hemorrhage volume was also correlated with vitamin D levels and maximum plaque thickness. Thirty-five patients underwent carotid endarterectomy, and histology-detected intraplaque hemorrhage was correlated with vitamin D levels and total plaque area. RESULTS: Low vitamin D levels ( P = .03) were a significant predictor of MR imaging detected intraplaque hemorrhage, along with plaque thickness (prevalence ratio = 1.40, P r = 0.45, P r = 0.26, P = .003). Additionally, histology-detected intraplaque hemorrhage area linearly correlated with plaque area (partial r = 0.46, P r = 0.22, P = .03). The association of intraplaque hemorrhage volume with low vitamin D levels was also higher with ischemic stroke. CONCLUSIONS: Low vitamin D levels and plaque thickness predict carotid intraplaque hemorrhage and outperform lumen markers of vulnerable plaque. This research demonstrates a significant link between low vitamin D levels and carotid intraplaque hemorrhage.

Introduction Heart failure (HF) is one of the leading causes of rehospitalization in the United States. Rehospitalizations are a costly outcome and are challenging to reduce due to multiple factors. Some interventions for reducing readmissions utilize predictive models to forecast adverse events such as mortality and rehospitalizations. Many rehospitalization risk scores were developed using hospital-based data from electronic health records (EHR). However, no rehospitalization risk score uses home healthcare EHR data. This study evaluated the production of a rehospitalization risk score using data from the Outcome and Assessment Information Set (OASIS) among home healthcare patients with HF after hospital discharge. Aim To produce a risk score for rehospitalization using OASIS among home healthcare patients with HF after hospital discharge. Methods This study was a secondary data analysis of the OASIS C version that was collected from January 1, 2011 to August 31, 2013. The dataset included N=836 patients. A multivariable logistic regression model was fitted to the rehospitalization outcome, using interactive backwards elimination variable selection. The final model included 9 predictor variables in a simple-to-use risk score that has a possible range (0 to 41). Regression coefficients were divided by the smallest regression coefficient and rounded to the nearest integer. For each patient risk factor, the integer weightings were summed to obtain the risk score. The predictive accuracy of the risk score was measured using the area under the receiver operating characteristic curve (i.e., c-statistic). The model was then internally validated using 10-fold cross validation. Results The median age was 79.5 years old, 43% were male, and 82% were white. We identified 9 significant risk factors: multiple hospitalization in the past 12 months, frequency of pain interfering, urinary incontinence, ability to grooming, ability to dress lower body, ability to feed, prior ability with everyday activities, the level of assistance, and Charlson comorbidity index score. For example, patients with grooming utensils must be placed within reach was a significantly greater risk compared to being able to groom self-unaided. The clinical prediction score which combined the patient's risk factors achieved a c-statistic of 0.64 (95%CI: 0.61 to 0.68). In the 10-fold cross-validation, the risk score had a c-statistic of 0.62 (95%CI: 0.58 to 0.65), which is the validated prediction accuracy expected in future home healthcare patients with HF. Conclusions This study developed a risk score for rehospitalization using OASIS among home healthcare patients with HF after hospital discharge. The risk scores of specific items such as the identified risk factors in this study could be an indicator of decision-making for personalized care.

Importance Posthospitalization follow-up visits are prescribed frequently for children with bronchiolitis. The rationale for this practice is unclear, but prior work has indicated that families value these visits for the reassurance provided. The overall risks and benefits of scheduled visits have not been evaluated. Objective To assess whether an as-needed posthospitalization follow-up visit is noninferior to a scheduled posthospitalization follow-up visit with respect to reducing anxiety among parents of children hospitalized for bronchiolitis. Design, Setting, and Participants This open-label, noninferiority randomized clinical trial, performed between January 1, 2018, and April 31, 2019, assessed children younger than 24 months of age hospitalized for bronchiolitis at 2 children’s hospitals (Primary Children’s Hospital, Salt Lake City, Utah, and Lucile Packard Children’s Hospital, Palo Alto, California) and 2 community hospitals (Intermountain Riverton Hospital, Riverton, Utah, and Packard El Camino Hospital, Mountain View, California). Data analysis was performed in an intention-to-treat manner. Interventions Randomization (1:1) to a scheduled (n = 151) vs an as-needed (n = 153) posthospitalization follow-up visit. Main Outcome and Measures The primary outcome was parental anxiety 7 days after hospital discharge, measured using the anxiety portion of the Hospital Anxiety and Depression Scale, which ranged from 0 to 28 points, with higher scores indicating greater anxiety. Fourteen prespecified secondary outcomes were assessed. Results Among 304 children randomized (median age, 8 months; interquartile range, 3-14 months; 179 [59%] male), the primary outcome was available for 269 patients (88%). A total of 106 children (81%) in the scheduled follow-up group attended a scheduled posthospitalization visit compared with 26 children (19%) in the as-needed group (absolute difference, 62%; 95% CI, 53%-71%). The mean (SD) 7-day parental anxiety score was 3.9 (3.5) among the as-needed posthospitalization follow-up group and 4.2 (3.5) among the scheduled group (absolute difference, −0.3 points; 95% CI, −1.0 to 0.4 points), with the upper bound of the 95% CI within the prespecified noninferiority margin of 1.1 points. Aside from a decreased mean number of clinic visits (absolute difference, −0.6 visits per patient; 95% CI, −0.4 to −0.8 visits per patient) among the as-needed group, there were no significant between-group differences in secondary outcomes, including readmissions (any hospital readmission before symptom resolution: absolute difference, −1.6%; 95% CI, −5.7% to 2.5%) and symptom duration (time from discharge to cough resolution: absolute difference, −0.6 days; 95% CI, −2.4 to 1.2 days; time from discharge to child reported “back to normal”: absolute difference, −0.8 days; 95% CI, −2.7 to 1.0 days; and time from discharge to symptom resolution: absolute difference, −0.6 days; 95% CI, −2.5 to 1.3 days). Conclusions and Relevance Among parents of children hospitalized for bronchiolitis, an as-needed posthospitalization follow-up visit is noninferior to a scheduled posthospitalization follow-up visit with respect to reducing parental anxiety. These findings support as-needed follow-up as an effective posthospitalization follow-up strategy. Trial Registration ClinicalTrials.gov Identifier:NCT03354325

BACKGROUND: Guidelines recommend a prolonged course (10 days) of intravenous (IV) antibiotic therapy for infants with uncomplicated, late-onset group B Streptococcus (GBS) bacteremia. Our objective was to determine the frequency with which shorter IV antibiotic courses are used and to compare rates of GBS disease recurrence between prolonged and shortened IV antibiotic courses. METHODS: We performed a multicenter retrospective cohort study of infants aged 7 days to 4 months who were admitted to children’s hospitals in the Pediatric Health Information System database from 2000 to 2015 with GBS bacteremia. The exposure was shortened IV antibiotic therapy, defined as discharge from the index GBS visit after a length of stay of ≤8 days without a peripherally inserted central catheter charge. The primary outcome was readmission for GBS bacteremia, meningitis, or osteomyelitis in the first year of life. Outcomes were analyzed by using propensity-adjusted, inverse probability–weighted regression models. RESULTS: Of 775 infants who were diagnosed with uncomplicated, late-onset GBS bacteremia, 612 (79%) received a prolonged IV course of antibiotic therapy, and 163 (21%) received a shortened course. Rates of treatment with shortened IV courses varied by hospital (range: 0%–67%; SD: 20%). Three patients (1.8%) in the shortened IV duration group experienced GBS recurrence, compared with 14 patients (2.3%) in the prolonged IV duration group (adjusted absolute risk difference: −0.2%; 95% confidence interval: −3.0% to 2.5%). CONCLUSIONS: Shortened IV antibiotic courses are prescribed among infants with uncomplicated, late-onset GBS bacteremia, with low rates of disease recurrence and treatment failure.

Nanotechnology produces a wide range of medicinal compounds, including nanoparticulate silver, which are increasingly introduced in various forms for consumer use. As with all medicinal compounds, potential drug interactions are an important consideration for ingested silver nanoparticles. Nanoparticulate silver-drug interactions may be mediated through induced oxidative stress in liver tissue where the majority of systemically bioavailable silver nanoparticles is found. To investigate whether an orally ingested commercially available colloidal silver nanoproduct produces pharmacokinetic interference on select cytochrome P450 enzymes, a prospective, single-blind, controlled in vivo human study using simultaneous administration of standardized probes for P450 enzyme classes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was conducted. Oral ingestion of a commercial colloidal silver nanoproduct produces detectable silver in human serum after 14 days of dosing. This silver, however, elicits no demonstrable clinically significant changes in metabolic, hematologic, urinary, physical findings or cytochrome P450 enzyme inhibition or induction activity. Given their increasingly broad, diverse human exposures, future characterization of human cytochrome P450 enzyme activity for other systemically bioavailable nanotechnology products are warranted.

Human biodistribution, bioprocessing and possible toxicity of nanoscale silver receive increasing health assessment. We prospectively studied commercial 10- and 32-ppm nanoscale silver particle solutions in a single-blind, controlled, cross-over, intent-to-treat, design. Healthy subjects (n=60) underwent metabolic, blood counts, urinalysis, sputum induction, and chest and abdomen magnetic resonance imaging. Silver serum and urine content were determined. No clinically important changes in metabolic, hematologic, or urinalysis measures were identified. No morphological changes were detected in the lungs, heart or abdominal organs. No significant changes were noted in pulmonary reactive oxygen species or pro-inflammatory cytokine generation. In vivo oral exposure to these commercial nanoscale silver particle solutions does not prompt clinically important changes in human metabolic, hematologic, urine, physical findings or imaging morphology. Further study of increasing time exposure and dosing of silver nanoparticulate silver, and observation of additional organ systems are warranted to assert human toxicity thresholds.In this study, the effects of commercially available nanoparticles were studied in healthy volunteers, concluding no detectable toxicity with the utilized comprehensive assays and tests. As the authors rightfully state, further studies are definitely warranted. Studies like this are much needed for the more widespread application of nanomedicine.

Background Despite promising epidemiological data, it remains unclear if increased blood pressure variability is associated with death after acute ischemic stroke. Our objective was to examine this association in a large cohort of acute ischemic stroke patients. Methods We conducted a retrospective analysis of anonymized, pooled, participant data from the Virtual International Stroke Trial Archive. We included patients with a 90-day modified Rankin Scale and blood pressure readings in the 24 h after study enrollment. The exposure was blood pressure variability during the day after study enrollment, calculated for the systolic and diastolic blood pressure using six statistical methodologies. The primary outcome was death within 90 days of stroke onset. Results Our cohort comprised 1891 patients of whom 277 (14.7%) died within 90 days. All indices of blood pressure variability were higher in patients who died, but the difference was more pronounced for systolic than diastolic blood pressure variability (systolic standard deviation for alive versus dead patients = 13.4 versus 15.9 mmHg, p

Enhanced in vitro human and ex vivo rat platelet aggregation from direct exposure to silver nanoparticles is previously reported. Given the increasing human use of engineered silver nanoscale products, platelet aggregation prompted by silver nanoparticles may contribute to human cardiovascular events. To understand how direct washed platelet exposure to silver nanoparticles translates to ex vivo platelet aggregation, the authors conducted a placebo-controlled, single-blind, dose-monitored, cross-over study design in 18 healthy human volunteers. After 2 weeks of daily oral silver nanoparticle ingestion, platelet aggregation was evaluated by light transmission aggregometry in response to collagen and ADP agonists, both at baseline and after silver nanoparticle or placebo diluent oral dosing. Final percent aggregation (PA) and the changes in PA were determined using a paired design (i.e., active and placebo solutions). Enhanced ex vivo platelet activation was not detectable at peak serum silver concentrations10 µg/L. Further studies of colloidal silver nanoparticles on human platelet activities are warranted.

In observational studies, higher uric acid levels are associated with metabolic syndrome, diabetes, and kidney disease.The objective of this study is to examine whether reduction of plasma uric acid with febuxostat, a xanthine oxido reductase inhibitor, impacts adipose tissue oxidative stress, adipokines, and markers of systemic inflammation or kidney fibrosis.This was a double-blinded randomized controlled trial.Academic university setting was used.Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included.Adipose tissue thiobarbituric acid reducing substances (TBARS) and adiponectin concentrations and urinary transforming growth factor-β (TGF-β) were primary endpoints. Plasma C-reactive protein, high molecular weight-adiponectin, interleukin-6, tumor necrosis factor-α, and TBARS and albuminuria were among predefined secondary endpoints.Participants were randomly assigned to febuxostat (n = 40) or matching placebo (n = 40) and followed for 24 weeks.Baseline plasma uric acid levels were 426 ± 83 µmol/L; 95% completed the study. Estimated glomerular filtration rate (eGFR) declined from 54 ± 17 mL/min/1.73 mRelatively modest sample size and short duration of follow-up.In this population with progressive diabetic nephropathy, febuxostat effectively reduced plasma uric acid. However, no detectable effects were observed for the prespecified primary or secondary endpoints.The study was registered in clinicaltrials.gov (NCT01350388).Dans les études observationnelles, des taux élevés d’acide urique sont associés à un syndrome métabolique, au diabète et à l’insuffisance rénale.Cette étude visait à déterminer si l’utilisation de febuxostat, un inhibiteur de la xanthine oxydoréductase, pour réduire le taux d’acide urique dans le plasma avait une incidence sur le stress oxydatif du tissu adipeux, les adipokines, les marqueurs de l’inflammation systémique ou sur la fibrose kystique.Il s’agit d’un essai à double insu, randomisé et contrôlé.L’étude s’est effectuée en contexte universitaire.Les participants à cette étude étaient des adultes obèses ou en surpoids, présentant une hyperuricémie ainsi qu’une néphropathie diabétique de type 2.Les critères principaux incluaient la concentration d’adiponectine et de substances réagissant avec l’acide thiobarbiturique (TBARS) dans les tissus adipeux, de même que le facteur de croissance transformant urinaire (TGF-β). Les critères secondaires incluaient les protéines C-réactives du plasma, l’adiponectine de poids moléculaire élevé, l’interleukine-6, le facteur de nécrose tumorale alpha, les TBARS ainsi que l’albuminurie.On a prescrit, de façon aléatoire, du febuxostat (n = 40) ou un placebo (n = 40) aux participants, et ces derniers ont été suivis sur une période de 24 semaines.Les valeurs initiales d’acide urique dans le plasma se situaient à 426 ± 83 µmol/L. La grande majorité des participants (95%) a complété l’étude. Le débit de filtration glomérulaire estimé a chuté de 54 ± 17 mL/min/1,73 mLa taille relativement modeste de l’échantillon, de même que la courte durée du suivi constituent les limites de l’étude.Dans la population observée, soit des patients atteints de néphropathie diabétique progressive, l’administration de fébuxostat a réduit de façon efficace les taux plasmatiques d’acide urique. Par ailleurs, aucun effet apparent n’a été observé sur les critères primaires et secondaires préétablis.Cette étude a été enregistrée sur clinicaltrials.gov (NCT01350388).

Background: With a lifetime prevalence of 16.2%, major depressive disorder is the fifth biggest contributor to the disease burden in the United States. Objective: The aim of this study, building on previous work qualitatively analyzing depression-related Twitter data, was to describe the development of a comprehensive annotation scheme (ie, coding scheme) for manually annotating Twitter data with Diagnostic and Statistical Manual of Mental Disorders, Edition 5 (DSM 5) major depressive symptoms (eg, depressed mood, weight change, psychomotor agitation, or retardation) and Diagnostic and Statistical Manual of Mental Disorders, Edition IV (DSM-IV) psychosocial stressors (eg, educational problems, problems with primary support group, housing problems). Methods: Using this annotation scheme, we developed an annotated corpus, Depressive Symptom and Psychosocial Stressors Acquired Depression, the SAD corpus, consisting of 9300 tweets randomly sampled from the Twitter application programming interface (API) using depression-related keywords (eg, depressed, gloomy, grief). An analysis of our annotated corpus yielded several key results. Results: First, 72.09% (6829/9473) of tweets containing relevant keywords were nonindicative of depressive symptoms (eg, “we’re in for a new economic depression”). Second, the most prevalent symptoms in our dataset were depressed mood and fatigue or loss of energy. Third, less than 2% of tweets contained more than one depression related category (eg, diminished ability to think or concentrate, depressed mood). Finally, we found very high positive correlations between some depression-related symptoms in our annotated dataset (eg, fatigue or loss of energy and educational problems; educational problems and diminished ability to think). Conclusions: We successfully developed an annotation scheme and an annotated corpus, the SAD corpus, consisting of 9300 tweets randomly-selected from the Twitter application programming interface using depression-related keywords. Our analyses suggest that keyword queries alone might not be suitable for public health monitoring because context can change the meaning of keyword in a statement. However, postprocessing approaches could be useful for reducing the noise and improving the signal needed to detect depression symptoms using social media. [J Med Internet Res 2017;19(2):e48]

Background: Direct oral anticoagulants (DOACs) have the potential to improve stroke prevention among atrial fibrillation (AF) patients. We sought to determine if oral anticoagulation (OAC) treatment rates have increased since the approval of DOACs. Methods: We identified 6,688 patients with AF at an academic medical center from January 2008 to June 2015. We examined OAC prescription rates over time and according to CHA2DS2VASc score using multivariable Poisson regression models, with an interaction term between risk score and year of AF diagnosis. Results: Among 6,688 AF patients, 78% had CHA2DS2VASc scores ≥2, 51.6% of whom received an OAC prescription within 90 days of diagnosis. The OAC prescription rate was 47.8% in the pre-DOAC era and peaked at 56.4% in 2014. Relative to the pre-DOAC era, prescription rates increased in 2012 and leveled off thereafter. The prescription rate for the highest risk group was 58.5%, compared with 45.0% in patients with a CHA2DS2VASc score of 2 (p < 0.01). In the adjusted analysis, prescription rates were higher for the higher risk group (adjusted relative risk 1.24 for CHA2DS2VASc score 7-9 vs. 2, 95% CI 1.09-1.40). Conclusions: OAC treatment rates have increased since DOAC introduction, but substantial treatment gaps remain, specifically among the higher risk patients.

Chronic kidney disease continues to be a major limiting factor for long-term survival of heart transplant recipients. Little is known about the early use of renin-angiotensin system (RAS) blocking agents and their impact on renal function and hemodynamics in heart transplant recipients. In this cohort study all eligible recipients of orthotopic heart transplants at the UTAH cardiac transplantation program from 2001 through 2007 were divided into 2 groups-patients who were started on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers within the first 4 weeks of transplantation and continued on these for ≥4 weeks during the first 3 months (RAS blockade group, n = 75) and those who were not (non-RAS blockade group, n = 52). All patients were followed for 1 year after transplantation. There were no significant differences at baseline between the 2 groups. Estimated glomerular filtration rate at 12 months was significantly higher in the RAS blockade group compared to the non-RAS blockade group (mean ± SD, 56.3 ± 22.4 vs 47.3 ± 18.1 ml/min/1.73 m(2), p = 0.036). At 12 months pulmonary artery systolic pressure was significantly lower in the RAS blockade group compared to the non-RAS blockade group (30.2 ± 7.4 vs 32.9 ± 9.3 mm Hg, p = 0.023). Left ventricular ejection fraction and pulmonary capillary wedge pressure were similar between the 2 groups. In conclusion, early RAS blockade after heart transplantation is safe, well tolerated, and associated with better renal function and hemodynamic profile at 1 year after transplantation.

OBJECTIVE: : To evaluate lactogenesis after early postpartum insertion of the etonogestrel contraceptive implant. METHODS: : Healthy peripartum women with healthy term newborns who desired the etonogestrel implant for contraception were randomly assigned to early (1-3 days) or standard (4-8 weeks) postpartum insertion. The primary outcomes time to lactogenesis stage II and lactation failure were documented by a validated measure. The noninferiority margin for the mean difference in time to lactogenesis stage II was defined as 8 additional hours. Secondary data (device continuation and contraceptive use breast milk analysis supplementation rates side effects and bleeding patterns) were collected at periodic intervals for 6 months. RESULTS: : Sixty-nine women were enrolled. Thirty-five were randomly assigned to early insertion and 34 to standard insertion. There were no statistically significant differences between the groups in age race parity mode of delivery use of anesthesia or prior breastfeeding experience. Early insertion was demonstrated to be noninferior to standard insertion in time to lactogenesis stage II (early: [mean+/-standard deviation] 64.3+/-19.6 hours; standard: 65.2+/-18.5 hours mean difference -1.4 hours 95% confidence interval [CI] -10.6 to 7.7 hours). Early insertion was also demonstrated to be noninferior to standard insertion in incidence of lactation failure (1/34 [3%] in the early insertion group 0/35 [0%] in the standard insertion group [risk difference 0.03 95% CI -0.02 to 0.08]). Use of formula supplementation was not significantly different between the groups. Milk composition at 6 weeks was not significantly different between the groups. CONCLUSION: : Breastfeeding outcomes were similar in women who underwent early compared with standard postpartum insertion of the etonogestrel implant. CLINICAL TRIAL REGISTRATION: : ClinicalTrials.gov www.clinicaltrials.gov NCT00847587. LEVEL OF EVIDENCE: : I.

Key Points Question Are there disparities in leukodystrophy diagnosis in patients of different racial and ethnic backgrounds? Findings This case-control study of 557 patients with a diagnosis of leukodystrophy found that US patients of racial/ethnic minorities, including those from black, black Hispanic, and white Hispanic backgrounds, were significantly less likely to be diagnosed with a leukodystrophy. Furthermore, leukodystrophy disease–associated gene allele frequencies were the same or higher in populations of Latino or African descent. Meaning Patients of racial/ethnic minorities are being underdiagnosed for leukodystrophies, which can result in a lack of treatment or insufficient treatment., This case-control study compares the likelihood of being diagnosed with a leukodystrophy among US pediatric and adolescent patients of different racial/ethnic backgrounds and examines the prevalence of genes associated with leukodystrophy among racial/ethnic groups to investigate whether there are disparities in leukodystrophy diagnosis in different racial backgrounds., Importance Inherited leukodystrophies are a group of neurological diseases affecting myelin that cause significant morbidities and death. Timely and correct diagnosis is important for initiating treatment, designing disease screening, and offering care and guidance to patients and families. Objective To determine whether there are disparities in leukodystrophy diagnosis in different racial backgrounds. Design, Setting, and Participants This case-control study involved a retrospective review of patients aged 18 years or younger who were diagnosed with 1 of 4 leukodystrophies (metachromatic leukodystrophy, X-linked adrenoleukodystrophy, Krabbe disease, and Hurler disease) in the US Children’s Hospital Association’s Pediatric Health Information System database from October 1, 2015, through September 30, 2017. Main Outcomes and Measures Leukodystrophy diagnosis and racial background of the patients were analyzed. Adjusted prevalence estimates of leukodystrophies were obtained by controlling for sex, insurance type, urban or rural status, 2010 median household income for patient zip code, number of inpatient days, and age at first visit. Pathogenic leukodystrophy gene allele frequencies in different racial backgrounds for ABCD1, ARSA, GALC, and IDUA were determined using the gnomAD database. Results Of the 557 patients identified with a leukodystrophy (221 [40%] female; 321 [58%] white non-Hispanic, 54 [10%] black non-Hispanic, and 51 [9%] white Hispanic; median [range] age, 7 [0-18] years), nonwhite race, including black non-Hispanic, black Hispanic, and white Hispanic, was associated with not having a leukodystrophy diagnosis. The adjusted prevalence for a leukodystrophy diagnosis in white non-Hispanic patients was 13.8 (95% CI, 10.6-17.9) per 100 000 patients, compared with 5.8 (95% CI, 3.8-8.9), 2.4 (95% CI, 1.1-5.2), and 7.4 (95% CI, 5.2-10.4) per 100 000 in black non-Hispanic, black Hispanic, and white Hispanic patients, respectively. This reduced rate of diagnosis was out of proportion to the frequency of the different races in the Pediatric Health Information System database. Similar or higher frequencies of missense or loss-of-function alleles were measured in populations of Latino and African descent for the pathogenic leukodystrophy gene alleles. For example, for ABCD1, allele frequencies in those of Latino or African descent were 2.1 × 10−5 and 2.2 × 10−5, as compared with 1.4 × 10−5 for those of European non-Finnish descent. Conclusions and Relevance Patients of racial/ethnic minorities, including those from black, black Hispanic, and white Hispanic backgrounds, were significantly less likely to be diagnosed with a leukodystrophy. Leukodystrophy disease–associated allele frequencies were the same or higher in populations of Latino or African descent, arguing against a genetic founder effect being responsible for the lower diagnosis rates. This underdiagnosis has implications for newborn screening programs and treatment access and may reflect a more widespread problem in pediatric neurological and orphan diseases.

Background: The Inter-Mountain Project on Antibiotic Resistance and Therapy (IMPART) is an intervention that addresses emerging antimicrobial resistance and the reduction of unnecessary antimicrobial use. Purpose: This study assesses the design and implementation of the community intervention component of IMPART. Methods: The study was conducted in 12 rural Utah and Idaho communities. Following initial implementation, the intervention was evaluated and redesigned based on health behavior theory. Community penetration and intercept interview data were analyzed using multi-level logistic regression. Results: Over 10% of interview respondents were familiar with IMPART. Those exposed to intervention materials tended to be younger, female, and more likely to have had a family member with recent respiratory illness. Of those who had seen the project Self-Care Guide, 62% reported having a copy and 32% had talked to others about the information it contained. Correct responses to antibiotic knowledge ques...