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Objective: The goal was to develop a universal and resource-efficient adaptive preventive intervention (API) for incoming first-year students as a bridge to indicated interventions to address alcohol-related risks. The aims were to examine: (a) API versus assessment-only control, (b) the different APIs (i.e., 4 intervention sequences) embedded in the study design, and (c) moderators of intervention effects on binge drinking. Method: A sequential multiple assignment randomized trial (SMART) included two randomizations: timing (summer before vs. first semester) of universal personalized normative feedback and biweekly self-monitoring and, for heavy drinkers, bridging strategy (resource email vs. health coaching invitation). Participants (N = 891, 62.4% female, 76.8% White) were surveyed at the end of first and second semesters. The primary outcome was binge drinking frequency (4+/5+ drinks for females/males); secondary outcomes were alcohol consequences and health services utilization. Results: API (vs. control) was not significantly associated with outcomes. There were no differences between embedded APIs. Among heavy drinkers, the resource email (vs. health coach invitation) led to greater health services utilization. Moderator analyses suggested students intending to pledge into Greek life benefited more from any API (vs. control; 42% smaller increase from precollege in binge drinking frequency). Conclusions: Although overall effects were not significant, students at high risk (i.e., entering fraternities/sororities) did benefit more from the intervention. Furthermore, the resource email was effective for heavier drinkers. A technology-based strategy to deliver targeted resource-light interventions for heavy drinkers may be effective for reducing binge drinking during the transition to college. What is the public health significance of this article?: The study examined the effect of adaptive preventive interventions (APIs), which are interventions tailored over time to better meet the needs of individuals, on college student drinking. In this case, the APIs did not have overall effects for the student population of incoming first-year college students, but the APIs did reduce binge drinking for students intending to pledge into fraternities or sororities. For heavy-drinking students, a resource email providing a link to an online intervention (i.e., Web-BASICS) was more effective in increasing health services utilization than an invitation to chat with an online health coach. Such technology-based strategies to deliver targeted interventions require minimal resources and may be effective for supporting health for high-risk students during the transition to college. [ABSTRACT FROM AUTHOR]

Adolescent school connectedness generally protects from risk behaviors such as tobacco use; however, its relationship to e-cigarette use is unclear. This study examines the relationship between adolescent school connectedness and e-cigarette susceptibility in a diverse longitudinal sample. This secondary analysis of a school-based intervention surveyed 608 middle (66%) and high school (34%) students from 10 schools at 3 time points over 1 year. At baseline, respondents had a mean age of 14 years, 54% were female, and 71% were BIPOC (Black, Indigenous, People of Color). Logistic regression models examined unadjusted and adjusted associations between school connectedness (both baseline and concurrent) and e-cigarette susceptibility over time. E-cigarettes represented the most prevalent form of current nicotine-containing product use in spring 2019 (2.3%), and most respondents reported no e-cigarette susceptibility (69%). E-cigarette susceptibility remained relatively stable during the study. Higher baseline school connectedness levels were associated with lower odds of e-cigarette susceptibility over time. Similarly, higher concurrent school connectedness scores were associated with lower odds of e-cigarette susceptibility over time: spring 2019 (OR, 0.39; 95% CI, 0.32, 0.47), fall 2019 (OR, 0.49; 95% CI, 0.34, 0.72), and spring 2020 (OR, 0.64; 95% CI, 0.47, 0.87). Findings were similar for middle and high school students and did not differ significantly after adjusting for other covariates. Adolescents’ school connectedness appears to protect from e-cigarette susceptibility over time, underscoring the importance of promoting positive school experiences to reduce adolescent risk e-cigarette use. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the changes to the polymer surface of drug-eluting stent (DES) during balloon expansion. The stents tested were manufactured by Abbott Laboratories, Boston Scientific, Cordis and Medtronic. After balloon expansion, the abluminal and adluminal polymer surfaces of all the DES were damaged and microparticles detached. Authors concluded that polymer damage and detached microparticles could theoretically contribute to DES-associated complications.

Temporal changes in kidney transplant outcomes for cystinosis are unknown. We used the SRTR to identify all kidney transplants performed for cystinosis in patients younger than 31 years between 1987 and 2017. We divided time into three equal eras (1987‐1997, 1998‐2007, and 2008‐2017) to assess changes in outcomes using Cox proportional and linear regression models. We examined 441 transplants in 362 patients. Age at ESRD progressively increased (12.1 vs 13.3 vs 13.4; P = .046). Eras 2 and 3 had lower risk of acute rejection (aHR 2 vs 1:0.45; P < .001) (aHR 3 vs 1:0.26; P < .001) and higher 5‐year mean GFR (difference 2 vs 1:9.2 mL/min/1.73 m2; P = .005) (difference 3 vs 1:12.9 mL/min/1.73 m2; P = .002) compared with era 1. Five‐year graft survival was similar across eras, but 5‐year patient survival was higher for era 2 (aHR: 0.25; P = .01). Seventy‐nine patients underwent retransplantation. Five‐year patient (94.2% vs 92.5%; P = .57) and graft survival (79.1% vs 74.1%; P = .52) were similar between primary and subsequent transplants. Age at ESRD, acute rejection, GFR at 5 years, and patient survival improved over time. Kidney retransplantation is associated with excellent outcomes in children and young adults with cystinosis. [ABSTRACT FROM AUTHOR]

• 200 H&N cancer patients under radiation treatment were analyzed. • We aim to predict post-treatment dysphagia. • Patient similarity was defined in terms of tumor location with respect to organs at risk. • Tumor location and predicted doses were used to stratify the cohort into 4 groups. • Patient groups were significantly correlated with dysphagia 6 months post treatment. Using a 200 Head and Neck cancer (HNC) patient cohort, we employ patient similarity based on tumor location, volume, and proximity to organs at risk to predict radiation-associated dysphagia (RAD) in a new patient receiving intensity modulated radiation therapy (IMRT). All patients were treated using curative-intent IMRT. Anatomical features were extracted from contrast-enhanced tomography scans acquired pre-treatment. Patient similarity was computed using a topological similarity measure, which allowed for the prediction of normal tissues' mean doses. We performed feature selection and clustering, and used the resulting groups of patients to forecast RAD. We used Logistic Regression (LG) cross-validation to assess the potential toxicity risk of these groupings. Out of 200 patients, 34 patients were recorded as having RAD. Patient clusters were significantly correlated with RAD (p <.0001). The area under the receiver-operator curve (AUC) using pre-established, baseline features gave a predictive accuracy of 0.79, while the addition of our cluster labels improved accuracy to 0.84. Our results show that spatial information available pre-treatment can be used to robustly identify groups of RAD high-risk patients. We identify feature sets that considerably improve toxicity risk prediction beyond what is possible using baseline features. Our results also suggest that similarity-based predicted mean doses to organs can be used as valid predictors of risk to organs. [ABSTRACT FROM AUTHOR]

Clustering is the task of identifying groups of similar subjects according to certain criteria. The AJCC staging system can be thought as a clustering mechanism that groups patients based on their disease stage. This grouping drives prognosis and influences treatment. The goal of this work is to evaluate the efficacy of machine learning algorithms to cluster the patients into discriminative groups to improve prognosis for overall survival (OS) and relapse free survival (RFS) outcomes. We apply clustering over a retrospectively collected data from 644 head and neck cancer patients including both clinical and radiomic features. In order to incorporate outcome information into the clustering process and deal with the large proportion of censored samples, the feature space was scaled using the regression coefficients fitted using a proxy dependent variable, martingale residuals, instead of follow-up time. Two clusters were identified and evaluated using cross validation. The Kaplan Meier (KM) curves between the two clusters differ significantly for OS and RFS (p-value < 0.0001). Moreover, there was a relative predictive improvement when using the cluster label in addition to the clinical features compared to using only clinical features where AUC increased by 5.7% and 13.0% for OS and RFS, respectively. [ABSTRACT FROM AUTHOR]

Hennepin Health, a Medicaid accountable care organization, began serving early expansion enrollees (very low-income childless adults) in 2012. It uses an integrated care model to address social and behavioral needs. We compared health care utilization in Hennepin Health with other Medicaid managed care in the same area from 2012 to 2014, controlling for demographics, chronic conditions, and enrollment patterns. Homelessness and substance use were higher in Hennepin Health. Overall adjusted results showed Hennepin Health had 52% more emergency department visits and 11% more primary care visits than comparators. Over time, modeling a 6-month exposure to Hennepin Health, emergency department and primary care visits decreased and dental visits increased; hospitalizations decreased nonsignificantly but increased among comparators. Subgroup analysis of high utilizers showed lower hospitalizations in Hennepin Health. Integrated, accountable care under Medicaid expansion showed some desirable trends and subgroup benefits, but overall did not reduce acute health care utilization versus other managed care. [ABSTRACT FROM AUTHOR]

• Retrospective analysis of 695 HPV+ oropharyngeal cancer patients. • Risk prediction using machine learning to predict toxicity and survival. • Pre-treatment anatomical information improves standard (AJCC-8) risk prediction. • Machine-learning derived patient stratifications improve outcome prediction. Evaluate the effectiveness of machine learning tools that incorporate spatial information such as disease location and lymph node metastatic patterns-of-spread, for prediction of survival and toxicity in HPV+ oropharyngeal cancer (OPC). 675 HPV+ OPC patients that were treated at MD Anderson Cancer Center between 2005 and 2013 with curative intent IMRT were retrospectively collected under IRB approval. Risk stratifications incorporating patient radiometric data and lymph node metastasis patterns via an anatomically-adjacent representation with hierarchical clustering were identified. These clusterings were combined into a 3-level patient stratification and included along with other known clinical features in a Cox model for predicting survival outcomes, and logistic regression for toxicity, using independent subsets for training and validation. Four groups were identified and combined into a 3-level stratification. The inclusion of patient stratifications in predictive models for 5-yr Overall survival (OS), 5-year recurrence free survival, (RFS) and Radiation-associated dysphagia (RAD) consistently improved model performance measured using the area under the curve (AUC). Test set AUC improvements over models with clinical covariates, was 9 % for predicting OS, and 18 % for predicting RFS, and 7 % for predicting RAD. For models with both clinical and AJCC covariates, AUC improvement was 7 %, 9 %, and 2 % for OS, RFS, and RAD, respectively. Including data-driven patient stratifications considerably improve prognosis for survival and toxicity outcomes over the performance achieved by clinical staging and clinical covariates alone. These stratifications generalize well to across cohorts, and sufficient information for reproducing these clusters is included. [ABSTRACT FROM AUTHOR]

Background: KT recipients have increased the risk of CVD. The incidence of post‐transplant CVEs among pediatric recipients has not been well‐characterized. Patients and Methods: Between 1963 and 2015, 884 pediatric (age: 0‐17 years old) recipients received 1058 KTs at our institution. The cumulative incidence of CVEs was analyzed. Statistical models were used to estimate risk factors for developing post‐transplant CVEs. Results: Overall median patient survival was 33 years (IQR: 18.7‐47). A total of 362 CVEs occurred in 161 (18.3%) patients at a median age of 20.5 years. Arrhythmias (18%) were most common. Cumulative risk of post‐transplant CVEs was 9% at 10 years, 17% at 20 years, 25% at 30 years, and 36% at 40 years. Development of post‐transplant CVEs was associated with increased mortality (HR 2.25 [95% CI 1.61‐3.14]); of those who developed a CVE and died, 22/51 (43.1%) died of CVD. Multivariable risk factors for post‐transplant CVEs included a history of pretransplant CVD (aHR 1.92 [1.18‐3.13] and graft failure (4.57 [3.13‐6.67]). Discussion: A pretransplant history of CVD and a failed graft are significant risk factors for the development of post‐transplant CVE. CVD increases the risk of post‐transplant death or graft loss. [ABSTRACT FROM AUTHOR]

Background Acute kidney injury (AKI) has been extensively studied in hospital settings. Limited data exist regarding outcomes for patients with outpatient AKI who are not subsequently admitted. We investigated whether outpatient AKI, defined by a 50% increase in creatinine (Cr), is associated with increased mortality and renal events. Methods In this retrospective study, outpatient serum Cr values from adults receiving primary care at a health system during an 18-month exposure period were used to categorize patients into one of five groups (no outpatient AKI, outpatient AKI with recovery, outpatient AKI without recovery, outpatient AKI without repeat Cr and no Cr). Principal outcomes of all-cause mortality and renal events (50% decline in estimated glomerular filtration rate to <30 mL/min/1.73 m2) were examined using Cox proportional hazards models. Results Among 384 869 eligible patients, 51% had at least one Cr measured during the exposure period. Outpatient AKI occurred in 1.4% of patients while hospital AKI occurred in only 0.3% of patients. The average follow-up was 5.3 years. Outpatient AKI was associated with an increased risk of all-cause mortality {adjusted hazard ratio [aHR] 1.90 [95% confidence interval (CI) 1.76–2.06]} and results were consistent across all AKI groups. Outpatient AKI was also associated with an increased risk of renal events [aHR 1.33 (95% CI 1.11–1.59)], even among those who recovered. Conclusions Outpatient AKI is more prevalent than inpatient AKI and is a risk factor for all-cause mortality and renal events, even among those who recover kidney function. Further research is necessary to determine risk factors and identify strategies for preventing outpatient AKI. [ABSTRACT FROM AUTHOR]

Objective: Practice parameters recommend systematic assessment of depression symptoms over the course of treatment to inform treatment planning; however, there are currently no guidelines regarding how to use symptom monitoring to guide treatment decisions for psychotherapy. The current study compared two time points (week 4 and week 8) for assessing symptoms during interpersonal psychotherapy for depressed adolescents (IPT-A) and explored four algorithms that use the symptom assessments to select the subsequent treatment.Method: Forty adolescents (aged 12-17 years) with a depression diagnosis began IPT-A with an initial treatment plan of 12 sessions delivered over 16 weeks. Adolescents were randomized to a week 4 or week 8 decision point for considering a change in treatment. Insufficient responders at either time point were randomized a second time to increased frequency of IPT-A (twice per week) or addition of fluoxetine. Measures were administered at baseline and weeks 4, 8, 12, and 16.Results: The week 4 decision point for assessing response and implementing treatment augmentation for insufficient responders was more efficacious for reducing depression symptoms than the week 8 decision point. There were significant differences between algorithms in depression and psychosocial functioning outcomes.Conclusion: Therapists implementing IPT-A should routinely monitor depression symptoms and consider augmenting treatment for insufficient responders as early as week 4 of treatment.Clinical Trial Registration Information: An Adaptive Treatment Strategy for Adolescent Depression. https://clinicaltrials.gov; NCT02017535. [ABSTRACT FROM AUTHOR]

Background: For many childhood cancers, survival is lower among non-Hispanic blacks and Hispanics in comparison with non-Hispanic whites, and this may be attributed to underlying socioeconomic factors. However, prior childhood cancer survival studies have not formally tested for mediation by socioeconomic status (SES). This study applied mediation methods to quantify the role of SES in racial/ethnic differences in childhood cancer survival.Methods: This study used population-based cancer survival data from the Surveillance, Epidemiology, and End Results 18 database for black, white, and Hispanic children who had been diagnosed at the ages of 0 to 19 years in 2000-2011 (n = 31,866). Black-white and Hispanic-white mortality hazard ratios and 95% confidence intervals, adjusted for age, sex, and stage at diagnosis, were estimated. The inverse odds weighting method was used to test for mediation by SES, which was measured with a validated census-tract composite index.Results: Whites had a significant survival advantage over blacks and Hispanics for several childhood cancers. SES significantly mediated the race/ethnicity-survival association for acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma, and non-Hodgkin lymphoma; SES reduced the original association between race/ethnicity and survival by 44%, 28%, 49%, and 34%, respectively, for blacks versus whites and by 31%, 73%, 48%, and 28%, respectively, for Hispanics versus whites ((log hazard ratio total effect - log hazard ratio direct effect)/log hazard ratio total effect).Conclusions: SES significantly mediates racial/ethnic childhood cancer survival disparities for several cancers. However, the proportion of the total race/ethnicity-survival association explained by SES varies between black-white and Hispanic-white comparisons for some cancers, and this suggests that mediation by other factors differs across groups. [ABSTRACT FROM AUTHOR]

Abstract: With increasing organ demand, living kidney donation from older donors (>60‐years‐old) has become more common. Between 1975 and 2014, 3752 donor nephrectomies (DN) were performed at University of Minnesota; 167 (4.5%) were >60‐years‐old Short‐ and long‐term outcomes were compared between contemporaneous >60‐years‐old and <60‐years‐old donors. On univariate analysis, >60‐years‐old were more likely to have had prior abdominal surgery and hypertension; and less likely to smoke. Baseline estimated glomerular filtration rate (eGFR) was lower in >60‐years‐old (80 ± 16 vs 101 ± 26 mL/min/1.73 m2; P < .001). Intraoperative and postoperative complications were similar, except a higher prevalence of <30 day ileus (3% vs 7%; P = .021) and longer postoperative length of stay (LOS) (4.2 vs 4.6 days; P = .005). On multivariate analysis, <30 day ileus and LOS continued to be significantly greater for >60‐years‐old After >20 years post‐DN, systolic blood pressure was significantly higher among >60‐years‐old (142 vs 125 mm Hg; P < .001) and HTN was diagnosed earlier (9 vs 14 years). After donation, eGFR was significantly lower for >60‐years‐old but slope of eGFR and rates of end‐stage renal disease (ESRD) were not significantly different >20 years post‐DN. Thus, kidney donation among carefully selected >60‐years‐old poses minimal perioperative risks and no added risk of long‐term ESRD. [ABSTRACT FROM AUTHOR]

The etiology of childhood cancers remains largely unknown, especially regarding environmental and behavioral risk factors. Unpacking the association between socioeconomic status (SES) and incidence may offer insight into such etiology. We tested associations between SES and childhood cancer incidence in a population-based case-cohort study (source cohort: Minnesota birth registry, 1989-2014). Cases, ages 0-14 years, were linked from the Minnesota Cancer Surveillance System to birth records through probabilistic record linkage. Controls were 4:1 frequency matched on birth year (2,947 cases and 11,907 controls). We tested associations of individual-level (maternal education) and neighborhood-level (census tract composite index) SES using logistic mixed models. In crude models, maternal education was positively associated with incidence of acute lymphoblastic leukemia (odds ratio (OR) = 1.10, 95% confidence interval (CI): 1.02, 1.19), central nervous system tumors (OR = 1.12, 95% CI: 1.04, 1.21), and neuroblastoma (OR = 1.15, 95% CI: 1.02,1.30). Adjustment for established risk factors--including race/ ethnicity, maternal age, and birth weight--substantially attenuated these positive associations. Similar patterns were observed for neighborhood-level SES. Conversely, higher maternal education was inversely associated with hepatoblastoma incidence (adjusted OR = 0.70, 95% CI: 0.51, 0.98). Overall, beyond the social patterning of established demographic and pregnancy-related exposures, SES is not strongly associated with childhood cancer incidence. [ABSTRACT FROM AUTHOR]

Background: Post-transplant malignancy (PTM) remains a concern among pediatric kidney transplant (PKT) recipients.Study Design: Between 1963 and 2015, 884 pediatric (age 0 to 17 years old) patients received 1,055 PKTs at our institution. Cox proportional hazards models were constructed to identify risk factors for PTM after PKT with time-to-first-PTM as a primary outcome. Secondly, the hazard of death or graft loss was calculated in patients who developed PTM.Results: Median patient survival was 33 years (interquartile range [IQR] 18.7 to 47 years); 260 patients died during the study period and 47 had been diagnosed with PTM. There were 235 PTMs that occurred in 136 (15.4%) recipients at a median age of 29 years (IQR 17.8 to 37 years). The percentages of patients with PTM were 13% at 20 years post-PKT and 26% at 30 years post-PKT. Of PTM patients who died, 63.8% died of PTM. Among those who developed PTM, there was a higher hazard of death or graft loss (hazard ratio [HR] 1.62; 95% CI 1.11 to 2.38). In multivariable proportional hazards models, factors associated with PTM were increasing age at PKT (adjusted HR [AHR] 3.14; 95% CI 1.80 to 5.48 for 14 to 17 year-olds compared with children less than 3 years), having a living unrelated donor (LURD; AHR 3.25; 95% CI 1.27 to 8.35 compared with a living related donor), or implanting an Epstein-Barr virus (EBV)-positive allograft in an EBV-negative recipient (AHR 5.66; 95% CI 1.11 to 29.0). Compared with the general population, the cancer rate for PKT recipients was 6 times higher (126 vs 21 per 100,000 person-years).Conclusions: Pediatric kidney transplant recipients are at increased risk of PTM, which adversely affects survival. Children receiving transplants at an older age, from a LURD, or who receive an EBV-positive organ, should be monitored closely for the development of PTM. [ABSTRACT FROM AUTHOR]

Background: Despite a highly recognized priority for public health and healthcare to implement population-level strategies to reduce the burden of cardiovascular disease (CVD), limited evidence exists on the most effective strategies. Data collection and evaluation of large scale, community based-prevention programs can be challenging and costly to achieve. The Heart of New Ulm (HONU) Project, begun in 2009, is a population-based initiative with healthcare, community, and workplace interventions addressing multiple levels of the social-ecological model designed to reduce modifiable CVD risk factors in rural New Ulm, MN. The community is served by one health system, enabling the use of electronic health record (EHR) data for surveillance. Objective: To assess trends for CVD risk factors, events, and healthcare utilization for New Ulm residents compared to a matched control population. Methods: We matched New Ulm residents (n = 4,077) with controls (n = 4,077) from a regional community served by the same health system using refined covariate balance techniques to match on baseline demographics, CVD risk factors, and health care utilization. Mixed effects longitudinal models with adjustment for age and gender, and an interaction for time by community, were run. Model based estimates were constructed for the entire cohort at each time period. Results: Over the first 6 years of the HONU Project, blood pressure, LDL, total cholesterol, and triglycerides were managed better in New Ulm than the matched comparison community. The proportion of New Ulm residents with controlled blood pressure increased by 6.2 percentage points while the control group increased by 2 points. 10-year ASCVD risk scores showed less decline for New Ulm residents than controls (16 vs. 18.4). The intervention and control groups did not differ with regard to inpatient stays, CVD events, smoking, or glucose. Conclusions: Compared to a matched control population, we found improved control of CVD risk factors in the New Ulm Population exposed to the HONU Project. [ABSTRACT FROM AUTHOR]

An individualized treatment rule (ITR) formalizes personalized medicine by assigning treatment as a function of patients' clinical information, which contrasts with a static treatment rule that assigns everyone the same treatment. ITR identification has become a common aim in randomized clinical trials but sample size considerations for this aim are lacking. One approach is to select a sample size that will reliably identify an ITR with a performance close to the theoretical optimal rule. However, this approach could still lead to identifying ITRs that perform worse than the optimal static rule, particularly in the absence of substantial effect heterogeneity. This limitation motivates sample size considerations aimed at reliable identification of a beneficial ITR, which outperforms the optimal static rule, and analysis methods that identify the estimated optimal static rule when there is substantial uncertainty about whether an ITR will improve outcomes. To address these limitations, we propose a sample size approach based on the probability of identifying a beneficial ITR and introduce an approach for selecting the LASSO penalty parameter such that in the absence of treatment effect heterogeneity the estimated optimal static rule is identified with high probability. We apply these approaches to the PLUTO trial aimed at developing methods to assist with smoking cessation. [ABSTRACT FROM AUTHOR]

Predicting an individual's risk of experiencing a future clinical outcome is a statistical task with important consequences for both practicing clinicians and public health experts. Modern observational databases such as electronic health records provide an alternative to the longitudinal cohort studies traditionally used to construct risk models, bringing with them both opportunities and challenges. Large sample sizes and detailed covariate histories enable the use of sophisticated machine learning techniques to uncover complex associations and interactions, but observational databases are often 'messy', with high levels of missing data and incomplete patient follow-up. In this paper, we propose an adaptation of the well-known Naive Bayes machine learning approach to time-to-event outcomes subject to censoring. We compare the predictive performance of our method with the Cox proportional hazards model which is commonly used for risk prediction in healthcare populations, and illustrate its application to prediction of cardiovascular risk using an electronic health record dataset from a large Midwest integrated healthcare system. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Single-nucleotide polymorphisms (SNPs) in the IL28B and PNPLA3 gene regions have been associated with hepatic steatosis in genotype 1 (G1) chronic HCV infection but their clinical impacts remain to be determined. Aim: We sought to validate these associations and to explore their impact on treatment response to peginterferon and ribavirin therapy. Methods: A total of 972 G1 HCV-infected Caucasian patients were genotyped for the SNPs rs12979860 (IL28B) and rs2896019 ( PNPLA3). Multivariable analysis tested IL28B and PNPLA3 for association with the presence of any steatosis (>0 %); clinically significant steatosis (>5 %); steatosis severity (grade 0-3/4); and the interacting associations of the SNPs and hepatic steatosis to sustained viral response (SVR). Results: IL28B and PNPLA3 polymorphisms were associated with the presence of any steatosis (rs12979860, p = 1.87 × 10; rs2896019, p = 7.56 × 10); clinically significant steatosis (rs12979860, p = 1.82 × 10; rs2896019, p = 1.27 × 10); and steatosis severity (rs12979860, p = 2.05 × 10; rs2896019, p = 2.62 × 10). Obesity, hypertriglyceridemia, hyperglycemia, liver fibrosis, and liver inflammation were all independently associated with worse steatosis. Hepatic steatosis was associated with lower SVR, and this effect was attenuated by IL28B. PNPLA3 had no independent association with SVR. Conclusions: IL28B and PNPLA3 are associated with hepatic steatosis prevalence and severity in Caucasians with G1 HCV, suggesting differing potential genetic risk pathways to steatosis. IL28B attenuates the association between steatosis and SVR. Remediable metabolic risk factors remain important, independently of these polymorphisms, and remain key therapeutic goals to achieve better outcomes for patients with HCV-associated hepatic steatosis. [ABSTRACT FROM AUTHOR]

College student alcohol use and associated negative consequences are clear public health problems with consequences including damage to self, others, and institutions. This paper describes the protocol of a research study designed to answer a number of important questions in the development of an adaptive preventive intervention (API) to reduce high-risk drinking among first-year college students. The API is designed to educate students and to motivate heavy-drinking college students to engage in existing resources to support reducing high-risk alcohol use, by leveraging technology-based intervention modalities. The primary outcome is a reduction in binge drinking, with secondary outcomes of reducing negative alcohol-related consequences and increasing health services utilization. Adaptive preventive interventions have the potential to reduce the acute and long-term negative health consequences of young adult alcohol use. [ABSTRACT FROM AUTHOR]

Kidney transplantation entails well‐coordinated complex care delivery. Patient‐provider cultural and linguistic discordance can lead to healthcare disparities. We analyzed kidney transplantation outcomes among our institution's Hmong recipients using a retrospective cohort study. From 1995 to 2015, 2164 adult (age ≥18) recipients underwent kidney transplantation at our institution; 78 self‐identified as Hmong. Survival rates were analyzed and compared to Caucasian recipients (n = 2086). Fifty (64.1%) Hmong recipients consistently requested interpreters. Mean follow‐up was 9.8 years for both groups. Hmong recipients (N = 78) were on average younger at transplant (45.7 vs 49.7 years; P = 0.02), more likely to be female (56% vs 38%; P = 0.001), and had higher gravidity (5.0 vs 1.9 births; P < 0.001). There were 13 (16.7%) Hmong living donor recipients, who were younger (32.8 vs 42.9 years; P = 0.006) at transplant compared to Caucasians (1429, 68.5%). Hmong 1‐ and 5‐year patient survival was 100%; Caucasians, 97.1% and 88% (P < 0.001). Hmong 1‐ and 5‐year graft survival was 98.7% and 84.9%; Caucasians 94.8% and 80.9% (P = 0.013). One‐ and 5‐year rejection‐free survival showed no difference (88.9% vs 82.4%; 86.7% vs 83.4%, P = 0.996). Despite cultural and linguistic differences between Hmong recipients and providers, we found no evidence of inferiority in KT outcomes in the Hmong population. [ABSTRACT FROM AUTHOR]

Background: Developing non-pharmacological interventions with strong potential to prevent or delay the onset of Alzheimer's disease (AD) in high-risk populations is critical. Aerobic exercise and cognitive training are two promising interventions. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective brain function intensively. Hence, combined aerobic exercise and cognitive training may have a synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested the effects of such a combined intervention, and the findings have been discrepant, largely due to varying doses and formats of the interventions.Methods/design: The purpose of this single-blinded, 2 × 2 factorial phase II randomized controlled trial is to test the efficacy and synergistic effects of a 6-month combined cycling and speed of processing training intervention on cognition and relevant mechanisms (aerobic fitness, cortical thickness, and functional connectivity in the default mode network) in older adults with amnestic mild cognitive impairment. This trial will randomize 128 participants equally to four arms: cycling and speed of processing, cycling only, speed of processing only, or attention control for 6 months, and then follow them for another 12 months. Cognition and aerobic fitness will be assessed at baseline and at 3, 6, 12, and 18 months; cortical thickness and functional connectivity at baseline and at 6, 12, and 18 months; Alzheimer's disease (AD) conversion at 6, 12, and 18 months. The specific aims are to (1) determine the efficacy and synergistic effects of the combined intervention on cognition over 6 months, (2) examine the underlying mechanisms of the combined intervention, and (3) calculate the long-term effect sizes of the combined intervention on cognition and AD conversion. The analysis will use intention-to-treat and linear mixed-effects modeling.Discussion: This trial will be among the first to test the synergistic effects on cognition and mechanisms (relevant to Alzheimer's-associated neurodegeneration) of a uniquely conceptualized and rigorously designed aerobic exercise and cognitive training intervention in older adults with mild cognitive impairment. It will advance Alzheimer's prevention research by providing precise effect-size estimates of the combined intervention.Trial Registration: ClinicalTrials.gov, NCT03313895 . Registered on 18 October 2017. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease, a global public health issue, accounts for 60 to 80% of all dementias. Alzheimer's disease primarily causes cognitive impairment and drugs have only modest short-term effects, highlighting a pressing need to develop effective interventions. Aerobic exercise holds promise for treating cognitive impairment in Alzheimer's disease through biologically sound mechanisms. Nonetheless, aerobic exercise studies in Alzheimer's disease are limited with mixed findings.Methods/design: This pilot randomized controlled trial will investigate the effects of a 6-month, individualized, moderate-intensity cycling intervention (20 to 50 minutes per session, 3 times a week) on cognition and hippocampal volume in community-dwelling older adults with mild-to-moderate Alzheimer's disease. The specific aims are to: 1) determine the immediate effect of the cycling intervention on cognition in Alzheimer's disease; 2) examine if the cycling intervention slows cognitive decline in Alzheimer's disease from baseline to 12 months; and 3) assess the effect of aerobic exercise on hippocampal volume over 12 months. Ninety subjects will be randomized on a 2:1 allocation ratio to cycling or attention control (low-intensity stretching) and followed for another 6 months. Allocations will be concealed to all investigators and outcome assessors will be blinded to group assignments and previous data. Cognition will be measured by the Alzheimer's disease Assessment Scale-Cognition at baseline before randomization and at 3, 6, 9, and 12 months. Hippocampal volume will be measured by magnetic resonance imaging at baseline and 6 and 12 months. The sample size of 90 will give 80% power to detect a 2.5-point difference in within-group changes in the Alzheimer's disease Assessment Scale-Cognition at 6 months for the cycling group.Discussion: Findings from this study will address the critical gap of exercise efficacy in Alzheimer's disease and use of magnetic resonance imaging as an outcome measure in clinical trials. This study will provide a potential treatment that may increase physical function and quality of life and curb the prohibitive costs for the growing dementia population.Trial Registration: Primary registration: (NCT01954550; date of registration: 20 September 2013). Secondary registration: (NCT01954550; date of registration: 1 October 2013). [ABSTRACT FROM AUTHOR]