Faculty Bibliography

IMPORTANCE: Acute aortic syndrome (AAS), a potentially fatal pathologic process within the aortic wall, should be suspected in patients presenting with severe thoracic pain and hypertension. AAS, including aortic dissection (approximately 90% of cases) and intramural hematoma, may be complicated by poor perfusion, aneurysm, or uncontrollable pain and hypertension. AAS is uncommon (approximately 3.5-6.0 per 100,000 patient-years) but rapid diagnosis is imperative as an emergency surgical procedure is frequently necessary. OBJECTIVE: To systematically review the current evidence on diagnosis and treatment of AAS. EVIDENCE REVIEW: Searches of MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials for articles on diagnosis and treatment of AAS from June 1994 to January 29, 2016, were performed. Only clinical trials and prospective observational studies of 10 or more patients were included. Eighty-two studies (2 randomized clinical trials and 80 observational) describing 57,311 patients were reviewed. FINDINGS: Chest or back pain was the most commonly reported presenting symptom of AAS (61.6%-84.8%). Patients were typically aged 60 to 70 years, male (50%-81%), and had hypertension (45%-100%). Sensitivities of computerized tomography and magnetic resonance imaging for diagnosis of AAS were 100% and 95% to 100%, respectively. Transesophageal echocardiography was 86% to 100% sensitive, whereas D-dimer was 51.7% to 100% sensitive and 32.8% to 89.2% specific among 6 studies (n = 876). An immediate open surgical procedure is needed for dissection of the ascending aorta, given the high mortality (26%-58%) and proximity to the aortic valve and great vessels (with potential for dissection complications such as tamponade). An RCT comparing endovascular surgical procedure to medical management for uncomplicated AAS in the descending aorta (n = 61) revealed no dissection-related deaths in either group. Endovascular surgical procedure was better than medical treatment (97% vs 43%, P < .001) for the primary end point of "favorable aortic remodeling" (false lumen thrombosis and no aortic dilation or rupture). The remaining evidence on therapies was observational, introducing significant selection bias. CONCLUSIONS AND RELEVANCE: Because of the high mortality rate, AAS should be considered and diagnosed promptly in patients presenting with acute chest or back pain and high blood pressure. Computerized tomography, magnetic resonance imaging, and transesophageal echocardiography are reliable tools for diagnosing AAS. Available data suggest that open surgical repair is optimal for treating type A (ascending aorta) AAS, whereas thoracic endovascular aortic repair may be optimal for treating type B (descending aorta) AAS. However, evidence is limited by the paucity of randomized trials.

BACKGROUND: The global economic crisis has been associated with increased unemployment and reduced public-sector expenditure on health care (PEH). We estimated the effects of changes in unemployment and PEH on cancer mortality, and identified how universal health coverage (UHC) affected these relationships. METHODS: For this longitudinal analysis, we obtained data from the World Bank and WHO (1990-2010). We aggregated mortality data for breast cancer in women, prostate cancer in men, and colorectal cancers in men and women, which are associated with survival rates that exceed 50%, into a treatable cancer class. We likewise aggregated data for lung and pancreatic cancers, which have 5 year survival rates of less than 10%, into an untreatable cancer class. We used multivariable regression analysis, controlling for country-specific demographics and infrastructure, with time-lag analyses and robustness checks to investigate the relationship between unemployment, PEH, and cancer mortality, with and without UHC. We used trend analysis to project mortality rates, on the basis of trends before the sharp unemployment rise that occurred in many countries from 2008 to 2010, and compared them with observed rates. RESULTS: Data were available for 75 countries, representing 2.106 billion people, for the unemployment analysis and for 79 countries, representing 2.156 billion people, for the PEH analysis. Unemployment rises were significantly associated with an increase in all-cancer mortality and all specific cancers except lung cancer in women. By contrast, untreatable cancer mortality was not significantly linked with changes in unemployment. Lag analyses showed significant associations remained 5 years after unemployment increases for the treatable cancer class. Rerunning analyses, while accounting for UHC status, removed the significant associations. All-cancer, treatable cancer, and specific cancer mortalities significantly decreased as PEH increased. Time-series analysis provided an estimate of more than 40,000 excess deaths due to a subset of treatable cancers from 2008 to 2010, on the basis of 2000-07 trends. Most of these deaths were in non-UHC countries. INTERPRETATION: Unemployment increases are associated with rises in cancer mortality; UHC seems to protect against this effect. PEH increases are associated with reduced cancer mortality. Access to health care could underlie these associations. We estimate that the 2008-10 economic crisis was associated with about 260,000 excess cancer-related deaths in the Organisation for Economic Co-operation and Development alone. FUNDING: None.

While the role of genetic risk factors in the etiology of uveal melanoma (UM) has been strongly suggested, the genetic susceptibility to UM is currently vastly unexplored. Due to shared epidemiological risk factors between cutaneous melanoma (CM) and UM, in this study we have selected 28 SNPs identified as risk variants in previous genome-wide association studies on CM or CM-related host phenotypes (such as pigmentation and eye color) and tested them for association with UM risk. By logistic regression analysis of 272 UM cases and 1782 controls using an additive model, we identified five variants significantly associated with UM risk, all passing adjustment for multiple testing. The three most significantly associated variants rs12913832 (OR = 0.529, 95% CI 0.415-0.673; p = 8.47E-08), rs1129038 (OR = 0.533, 95% CI 0.419-0.678; p = 1.19E-07) and rs916977 (OR = 0.465, 95% CI 0.339-0.637; p = 3.04E-07) are correlated (r(2) > 0.5) and map at 15q12 in the region of HERC2/OCA2, which determines eye-color in the human population. Our data provides first evidence that the genetic factors associated with pigmentation traits are risk loci of UM susceptibility.

IMPORTANCE:High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiovascular risk and could be approved in the United States for clinical use soon. However, data linking long-term temporal change in hs-cTnT to outcomes are limited, particularly in primary prevention settings. OBJECTIVE:To examine the association of 6-year change in hs-cTnT with incident coronary heart disease (CHD), heart failure (HF), and all-cause mortality. DESIGN, SETTING, AND PARTICIPANTS:This prospective observational cohort study, performed from January 1, 1990, to December 31, 2011, included 8838 participants with biracial representation from the Atherosclerosis Risk in Communities Study who were initially free of CHD and HF and who had hs-cTnT measured twice, 6 years apart. Data analysis was performed from October 28, 2014, to March 9, 2016. MAIN OUTCOME AND MEASURES:Risk factor and temporal hs-cTnT data were collected. Using Cox proportional hazards regression, we examined the association of hs-cTnT change with subsequent CHD, HF, and death during a maximum of 16 years. Improvement in discrimination was determined by the Harrell C statistic. RESULTS:Of the 8838 participants (mean age, 56 years; 5215 female [59.0%]; 1891 black [21.4%]) there were 1157 CHD events, 965 HF events, and 1813 deaths overall. Incident detectable hs-cTnT (baseline, <0.005 ng/mL; follow-up, ≥0.005 ng/mL) was independently associated with subsequent CHD (hazard ratio [HR], 1.4; 95% CI, 1.2-1.6), HF (HR, 2.0; 95% CI, 1.6-2.4), and death (HR, 1.5; 95% CI, 1.3-1.7), relative to an hs-cTnT level less than 0.005 ng/mL at both visits. In addition, HRs as high as 4 for CHD and death and 8 for HF were recorded among individuals with the most marked hs-cTnT increases (eg, baseline, < 0.005 ng/mL; follow-up, ≥0.014 ng/mL). Risk for subsequent outcomes was lower among those with relative hs-cTnT reductions greater than 50% from baseline. Furthermore, information on hs-cTnT change improved discrimination for HF and death when added to a model that included traditional risk factors, N-terminal pro-brain natriuretic peptide, and baseline hs-cTnT level. Among individuals with adjudicated HF hospitalizations, hs-cTnT change appeared to be similarly associated with HF with reduced and preserved ejection fraction. CONCLUSIONS AND RELEVANCE:Temporal increases in hs-cTnT, suggestive of progressive myocardial damage, are independently associated with incident CHD, death, and, above all, HF. Serial determination of hs-cTnT trajectory adds clinically relevant information to baseline testing and may be useful in prognostic assessments and the targeting of prevention strategies to high-risk individuals, especially among persons with stage A or B HF.

BACKGROUND: An Audio Computer-assisted Self Interview (ACASI) version of the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) could reduce barriers to substance use screening and assessment in primary care settings. This study evaluated the diagnostic accuracy of an ACASI ASSIST for identification of unhealthy substance use and substance use disorders (SUD). METHODS: 399 adult patients were consecutively recruited from an urban safety-net primary care clinic. ACASI ASSIST scores for tobacco, alcohol, marijuana, and cocaine were compared against reference standard measures to assess the instrument's diagnostic accuracy for identifying unhealthy use and SUD, first using empirically-derived optimal cutoffs, and second using the currently recommended ASSIST cutoffs. RESULTS: For identifying any unhealthy use, at the empirically-derived cutoffs the ACASI ASSIST had 93.6% sensitivity and 85.8% specificity (AUC=0.90) for tobacco, 85.9% sensitivity and 60.3% specificity (AUC=0.73), for alcohol in men, 100% sensitivity and 62.4% specificity (AUC=0.81) for alcohol in women, 94.6% sensitivity and 81.6% specificity (AUC=0.88) for marijuana, and 86.1% sensitivity, 84.0% specificity (AUC=0.85) for cocaine. For SUD, sensitivity ranged from 79% (for alcohol in males), to 100% (for tobacco), and specificity was 83% or higher (AUCs ranged 0.83-0.91). For substances other than tobacco, empirically-derived cutoff scores were lower than the standard cutoffs, and resulted in higher sensitivity and lower specificity for identifying unhealthy substance use. CONCLUSIONS: The ACASI ASSIST is a valid measure of unhealthy use and SUD for substances that are commonly used by primary care patients, and could facilitate effective and efficient screening for substance use in medical settings.