Faculty Bibliography

BACKGROUND:Optimal management of acute type B aortic dissection with retrograde arch extension is controversial. The effect of retrograde arch extension on operative and long-term mortality has not been studied and is not incorporated into clinical treatment pathways. METHODS:The International Registry of Acute Aortic Dissection was queried for all patients presenting with acute type B dissection and an identifiable primary intimal tear. Outcomes were stratified according to management for patients with and without retrograde arch extension. Kaplan-Meier survival curves were constructed. RESULTS:Between 1996 and 2014, 404 patients (mean age, 63.3 ± 13.9 years) were identified. Retrograde arch extension existed in 67 patients (16.5%). No difference in complicated presentation was noted (36.8% vs 31.7%, p = 0.46), as defined by limb or organ malperfusion, coma, rupture, and shock. Patients with or without retrograde arch extension received similar treatment, with medical management in 53.7% vs 56.5% (p = 0.68), endovascular treatment in 32.8% vs 31.1% (p = 0.78), open operation in 11.9% vs 9.5% (p = 0.54), or hybrid approach in 1.5% vs 3.0% (p = 0.70), respectively. The in-hospital mortality rate was similar for patients with (10.7%) and without (10.4%) retrograde arch extension (p = 0.96), and 5-year survival was also similar at 78.3% and 77.8%, respectively (p = 0.27). CONCLUSIONS:The incidence of retrograde arch dissection involves approximately 16% of patients with acute type B dissection. In the International Registry of Acute Aortic Dissection, this entity seems not to affect management strategy or early and late death.

PURPOSE:Intimate partner violence (IPV) affects one in three women globally, with adolescent and young adult women at highest risk. Less is known about IPV perpetration. We compare the prevalence and correlates of IPV perpetration among 15- to 19-year-old adolescent males in Baltimore (United States), Johannesburg (South Africa), Delhi (India), and Shanghai (China). METHODS:A cross-sectional survey was conducted in 2013 with males aged 15-19 recruited via respondent-driven sampling from disadvantaged neighborhoods in four cities: Baltimore (United States), New Delhi (India), Johannesburg (South Africa), and Shanghai (China); total n = 751 ever-partnered men. We describe the prevalence of past-year physical and sexual IPV perpetration and evaluate associations with gender norm attitudes, mental health, substance use, victimization experiences, and demographic factors. RESULTS:Past-year physical or sexual IPV perpetration ranged from 9% in Shanghai to 40% in Johannesburg. Factors associated with past-year perpetration across multiple sites included: binge drinking (Johannesburg adjusted odds ratio [AOR] = 2.8, Baltimore AOR = 6.7, and Shanghai AOR = 3.2), depressive symptoms (Johannesburg AOR = 2.4 and Shanghai AOR = 2.2), victimization in the home (Baltimore AOR = 2.5, Shanghai AOR = 2.7, and Johannesburg AOR = 1.7), and community violence victimization (Baltimore AOR = 7.0, Delhi AOR = 4.1, and Johannesburg AOR = 2.8). Equitable gender norm attitudes were protective against IPV perpetration in Johannesburg and Shanghai. Demographic factors (e.g., age, employment, and education) were inconsistently associated with IPV perpetration across sites. CONCLUSIONS:Past-year IPV perpetration was prevalent with differences identified across settings. Findings suggest the need to scale up evidence-based interventions targeting adolescents in disadvantaged urban communities in order to address many modifiable factors associated with IPV perpetration in this study.

BACKGROUND: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. METHODS: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. RESULTS: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. CONCLUSIONS: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00957359.

In Puerto Rico (PR), cancer is the leading cause of death. Previous research has identified the need for cancer education in PR. Using culturally adapted cancer curricula to train local health educators may effectively increase cancer education and reduce health disparities. This article describes the three-phase process used to transcreate the Cancer 101 curriculum to train Master of Public Health (MPH) students to educate PR communities. First, an expert panel collaboratively reviewed the curriculum for content, legibility, utility, and colloquialisms. Recommendations included incorporating local references and resources, replacing words and examples with culturally relevant topics, and updating objectives and evaluation items. Subsequent focus groups with 10 MPH students assessed the adaptation's strengths, weaknesses, and utility for future trainees. Participants were satisfied with the curriculum's overall adaptation, ease of use, and listed resources; further improvements were suggested for all modules. Final expert panel revisions highlighted minor feedback, with the final curriculum containing nine transcreated modules. The transcreation process identified the need for changes to content and cultural translation. Changes were culturally and literacy-level appropriate, represented PR's social context, and were tailored for future trainees to successfully deliver cancer education. Findings highlight the importance of adapting Spanish educational materials across Hispanic sub-groups.

STUDY OBJECTIVE: Perioperative thrombotic complications after orthopedic surgery are associated with significant morbidity and mortality. The use of aspirin to reduce perioperative cardiovascular complications in certain high-risk cohorts remains controversial. Few studies have addressed aspirin use, bleeding, and cardiovascular outcomes among high-risk patients undergoing joint and spine surgery. DESIGN/SETTING/PATIENTS: We performed a retrospective comparison of adults undergoing knee, hip, or spine surgery at a tertiary care center during 2 periods between November 2008 and December 2009 (reference period) and between April 2013 and December 2013 (contemporary period). MEASUREMENTS: Patient demographics, comorbidities, management, and outcomes were ascertained using hospital datasets. MAIN RESULTS: A total of 5690 participants underwent 3075 joint and spine surgeries in the reference period and 2791 surgeries in the contemporary period. Mean age was 61+/-13 years, and 59% were female. In the overall population, incidence of myocardial injury (3.1% vs 5.8%, P<.0001), hemorrhage (0.2% vs 0.8%, P=.0009), and red blood cell transfusion (17.2% vs 24.8%, P<.001) were lower in the contemporary period. Among 614 participants with a preoperative diagnosis of coronary artery disease (CAD), in-hospital aspirin use was significantly higher in the contemporary period (66% vs 30.7%, P<.0001); numerically, fewer participants developed myocardial injury (13.5% vs 19.3%, P=.05), had hemorrhage (0.3% vs 2.1%, P=.0009), and had red blood cell transfusion (37.2% vs 44.2%, P<.001) in the contemporary vs reference period. CONCLUSIONS: In a large tertiary care center, the incidence of perioperative bleeding and cardiovascular events decreased over time. In participants with CAD, perioperative aspirin use increased and appears to be safe.

Networks inference problems are commonly found in multiple biomedical subfields such as genomics, metagenomics, neuroscience, and epidemiology. Networks are useful for representing a wide range of complex interactions ranging from those between molecular biomarkers, neurons, microbial communities, to those found in human or animal populations. Recent technological advances have resulted in an increasing amount of healthcare data in multiple modalities, increasing the preponderance of network inference problems. Multi-domain data can now be used to improve the robustness and reliability of recovered networks from unimodal data. For infectious diseases in particular, there is a body of knowledge that has been focused on combining multiple pieces of linked information. Combining or analyzing disparate modalities in concert has demonstrated greater insight into disease transmission than could be obtained from any single modality in isolation. This has been particularly helpful in understanding incidence and transmission at early stages of infections that have pandemic potential. Novel pieces of linked information in the form of spatial, temporal, and other covariates including high-throughput sequence data, clinical visits, social network information, pharmaceutical prescriptions, and clinical symptoms (reported as free-text data) also encourage further investigation of these methods. The purpose of this review is to provide an in-depth analysis of multimodal infectious disease transmission network inference methods with a specific focus on Bayesian inference. We focus on analytical Bayesian inference-based methods as this enables recovering multiple parameters simultaneously, for example, not just the disease transmission network, but also parameters of epidemic dynamics. Our review studies their assumptions, key inference parameters and limitations, and ultimately provides insights about improving future network inference methods in multiple applications.

BACKGROUND: Preterm birth (PTB) rates (11.4% in 2013) in the United States (US) remain high and are a substantial cause of morbidity. Studies of prenatal exposure have associated particulate matter <2.5microns in diameter (PM2.5) and other ambient air pollutants with adverse birth outcomes, yet, to our knowledge, burden and costs of PM 2.5-attributable PTB have not been estimated in the US. OBJECTIVES: To estimate burden of PTB in the US and economic costs attributable to PM2.5 exposure in 2010. METHODS: Annual deciles of PM2.5 were obtained from US EPA. We converted PTB odds ratio (OR), identified in a previous meta-analysis (1.15 per 10microg/m3 for our base case, 1.07-1.16 for low- and high-end scenarios) to relative risk (RRs), to obtain an estimate that better represents the true relative risk. A reference level (RL) of 8.8microg/m3 was applied. We then used the RR estimates and county-level PTB prevalence to quantify PM2.5 attributable PTB. Direct medical costs were obtained from the 2007 Institute of Medicine report, and lost economic productivity (LEP) was estimated using a meta-analysis of PTB-associated IQ loss, and well-established relationships of IQ loss with LEP. All costs were calculated using 2010 dollars. RESULTS: An estimated 3.32% of PTBs nationally (corresponding to15,808 PTBs) in 2010 could be attributed to PM2.5 (PM2.5>8.8 microg/m3). Attributable PTBs cost were estimated at $4.33 billion (SA: $2.06-8.22B), of which $760 million were spent for medical care (SA: $362M-1.44B). The estimated PM2.5-attributable fraction (AF) of PTB was highest in urban counties, with highest AFs in the Ohio valley and Southern US. CONCLUSIONS: PM2.5 may contribute substantially to burden and costs of PTB in the US, and considerable health and economic benefits could be achieved through environmental regulatory interventions that reduce PM2.5 exposure in pregnancy.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison. METHODS: We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure-response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure-response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (euro1=$1.33). FINDINGS: The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2.33% of GDP] vs $217 billion [1.28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12.6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion). INTERPRETATION: EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention. FUNDING: Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation.