Risk assessment of acute pulmonary embolism utilizing coronary artery calcifications in patients that have undergone CT pulmonary angiography and transthoracic echocardiography.

OBJECTIVE: To evaluate the relation of coronary artery calcifications (CAC) on non-ECG-gated CT pulmonary angiography (CTPA) with short-term mortality in patients with acute pulmonary embolism (PE). METHODS: We retrospectively included all in-patients between May 2007 and December 2014 with an ICD-9 code for acute PE and CTPA and transthoracic echocardiography available. CAC was qualitatively graded as absent, mild, moderate, or severe. Relations of CAC with overall and PE-related 30-day mortality were assessed using logistic regression analyses. The independence of those relations was assessed using a nested approach, first adjusting for age and gender, then for RV strain, peak troponin T, and cardiovascular risk factors for an overall model. RESULTS: Four hundred seventy-nine patients were included (63 ± 16 years, 52.8% women, 47.2% men). In total, 253 (52.8%) had CAC-mild: 143 (29.9%); moderate: 89 (18.6%); severe: 21 (4.4%). Overall mortality was 8.8% (n = 42) with higher mortality with any CAC (12.6% vs. 4.4% without; odds ratio [OR] 3.1 [95%CI 2.1-14.5]; p = 0.002). Mortality with severe (19.0%; OR 5.1 [95%CI 1.4-17.9]; p = 0.011), moderate (11.2%; OR 2.7 [95%CI 1.1-6.8]; p = 0.031), and mild CAC (12.6%; OR 3.1 [95%CI 1.4-6.9]; p = 0.006) was higher than without. OR adjusted for age and gender was 2.7 (95%CI 1.0-7.1; p = 0.050) and 2.6 (95%CI 0.9-7.1; p = 0.069) for the overall model. PE-related mortality was 4.0% (n = 19) with higher mortality with any CAC (5.9% vs. 1.8% without; OR 3.5 [95%CI 1.1-10.7]; p = 0.028). PE-related mortality with severe CAC was 9.5% (OR 5.8 [95%CI 1.0-34.0]; p = 0.049), with moderate CAC 6.7% (OR 4.0 [95%CI 1.1-14.6]; p = 0.033), and with mild 4.9% (OR 2.9 [95%CI 0.8-9.9]; p = 0.099). OR adjusted for age and gender was 4.2 (95%CI 0.9-20.7; p = 0.074) and 3.4 (95%CI 0.7-17.4; p = 0.141) for the overall model. Patients with sub-massive PE showed similar results. CONCLUSION: CAC is frequent in acute PE patients and associated with short-term mortality. Visual assessment of CAC may serve as an easy, readily available tool for early risk stratification in those patients. KEY POINTS: • Coronary artery calcification assessed on computed tomography pulmonary angiography is frequent in patients with acute pulmonary embolism. • Coronary artery calcification assessed on computed tomography pulmonary angiography is associated with 30-day overall and PE-related mortality in patients with acute pulmonary embolism. • Coronary artery calcification assessed on computed tomography pulmonary angiography may serve as an additional, easy readily available tool for early risk stratification in those patients.

Multimodality Assessment of Right Ventricular Strain in Patients With Acute Pulmonary Embolism.

Optimal risk stratification is essential in managing patients with an acute pulmonary embolism (PE). There are limited data evaluating the potential additive value of various methods of evaluation of right ventricular (RV) strain in PE. We retrospectively evaluated RV strain by computed tomography (CT), transthoracic echocardiography (TTE), electrocardiography (ECG), and troponin levels in consecutive hospitalized patients with acute PE (May 2007 to December 2014). Four-hundred and seventy-seven patients met inclusion criteria. RV strain on ECG (odds ratio [OR] 1.9, confidence interval [CI] 1.1 to 3.3; p = 0.03), CT (OR 2.7, CI 1.5 to 4.8, p <0.001), TTE (OR 2.8, CI 1.5 to 5.4, p <0.001), or a positive troponin (OR 2.7, CI 2.0 to 6.9, p <0.001) were associated with adverse events. In patients with ECG, CT, and TTE data, increased risk was only elevated with RV strain on all 3 parameters (OR 4.6, CI 1.8 to 11.3, p <0.001). In all patients with troponin measurements, risk was only elevated with RV strain on all 3 parameters plus a positive troponin (OR 8.8, CI 2.8 to 28.1, p <0.001) and was similar in intermediate-risk PE (OR 11.1, CI 1.2 to 103.8, p = 0.04). In conclusion, in patients with an acute PE and evaluation of RV strain by ECG, CT, and TTE, risk of adverse events is only elevated when RV strain is present on all 3 modalities. Troponin further aids in discriminating high-risk patients. Multimodality assessment of RV strain is identified as a superior approach to risk assessment.

Pharmacokinetics and Safety Assessment of l-Tetrahydropalmatine in Cocaine Users: A Randomized, Double-Blind, Placebo-Controlled Study.

Cocaine use disorder (CUD) remains a significant public health challenge. l-Tetrahydropalmatine (l-THP), a well-tolerated and nonaddictive compound, shows promise for the management of CUD. Its pharmacologic profile includes blockade at dopamine and other monoamine receptors and attenuation of cocaine self-administration, reinstatement, and rewarding properties in rats. This study evaluated the safety of l-THP in human cocaine users and its influence on the safety and pharmacokinetics (PK) of cocaine. Twenty-four cocaine-using adult men were randomized to receive l-THP (30 mg twice a day orally) or placebo double-blind for 4 days, with an intranasal cocaine (40 mg) challenge on the fourth day. Safety and tolerability were evaluated using vital signs, ECG, clinical laboratory tests, and standardized self-report instruments. Peripheral venous blood was collected periodically and later assayed for l-THP and cocaine using highly sensitive and specific ultraperformance liquid chromatography-fluorescence detection (UPLC-FLD) methods. Twenty subjects completed the study, of whom 19 provided complete PK data. The short 3.5-day course of l-THP was safe and well tolerated and did not affect cocaine's PK or its acute cardiovascular effects. The cocaine AUC0→∞ was 211.5 and 261.4 h·ng/mL, and the Cmax was 83.3 and 104.5 ng/mL for the l-THP and placebo groups, respectively. In addition there were no significant differences in the number of side effects reported in each group (l-THP group 22 [48%], placebo group 24 [52%]) or vital signs including, heart rate, blood pressure, complete blood count, or ECG. These findings suggest that oral THP has promise for further development as a treatment for CUD.

Cervical cancer screening and acute care visits among Medicaid enrollees with mental and substance use disorders.

OBJECTIVE: This study compared rates of cervical cancer screening and acute care (primary or gynecological) visits among women with and without a diagnosis of psychosis, substance use disorder, bipolar disorder or mania, or depression. METHODS: Using data about women (N=105,681) enrolled in Maryland's Medicaid program in fiscal year 2005, the authors constructed logistic models with cancer screening and acute care visits as dependent variables and serious mental illness flags as independent variables. Covariates were age, race, geography, Medicaid eligibility category, and sexually transmitted diseases. The logistic model of cervical cancer screening outcomes was repeated with acute care visits as a covariate. RESULTS: Women with psychosis (N=4,747), bipolar disorder or mania (N=3,319), or depression (N=5,014) were significantly (p<.05) more likely than women in a control group without such disorders (N=85,375) to receive cancer screening (adjusted odds ratio (AOR) range=1.46-1.78) and to have associated acute care visits (AOR range=1.45-2.15). Compared with those in the control group, women with a substance use disorder, with (N=1,104) or without (N=6,122) psychosis, demonstrated reduced odds of cancer screening (AOR=.80) but similar odds of acute care visits (AOR=1.04). Acute care visits were strongly correlated with cancer screens. Genital cancer prevalence did not significantly differ among diagnostic groups. CONCLUSIONS: In Maryland Medicaid, the odds of cancer screening and related acute care visits were greater for women with major mental disorders compared with women in the control group. For women with substance use disorders, however, screening was reduced and acute care visits were similar compared with women in the control group. Providers should encourage and support their patients with substance use disorders to increase use of preventive care services by primary care physicians and gynecologists.

Alcohol and cannabis use and mortality in people with schizophrenia and related psychotic disorders.

The impact of co-morbid substance use on mortality is not well studied in psychotic disorders. The objective of this study was to examine the impact of substance use on mortality in people with psychotic disorders and alcohol and/or drug use. We examined the rate of substance use and the risk of substance use on mortality risk over a 4-10 year period in 762 people with psychotic disorders. Deceased patients were identified from the Social Security Death Index and the Maryland Division of Vital Records. Substance use was defined as regular and heavy use or abuse or dependence. Seventy seven percent had co-morbid lifetime substance use, with co-morbid cannabis and alcohol use occurring most commonly. Out of 762 subjects, 62 died during follow up. In a Cox model, predicted mortality risk was higher in age group 35-55 compared to <35 years and in males, but reduced in cannabis users. Overall five- (3.1% vs 7.5%) and ten-year mortality risk (5.5% vs. 13.6%) was lower in cannabis users than in non-users with psychotic disorders (p = 0.005) in a survival model. Alcohol use was not predictive of mortality. We observed a lower mortality risk in cannabis-using psychotic disorder patients compared to cannabis non-users despite subjects having similar symptoms and treatments. Future research is warranted to replicate these findings and to shed light on the anti-inflammatory properties of the endocannabinoid system and its role in decreased mortality in people with psychotic disorders.

Cigarette smoking and mortality risk in people with schizophrenia.

This study examined effects of cigarette smoking on mortality risk in 1213 persons aged 19-69 years with schizophrenia-related psychotic disorders admitted to State of Maryland Hospitals between 1994 and 2000. Inpatient medical records from 7 hospitals were reviewed to obtain demographic information, diagnosis, medication use, as well as smoking and other substance use. Social Security Death Index data were used to identify deaths in the study group between 1994 and 2004. Death records were reviewed to obtain manner of death and underlying disorders. Of the 1213, 55% were smokers and 71% abused substances. There was an age × smoking interaction (χ(2) = 14.6, df = 1, P = .0001) for mortality, with estimated hazard ratios (HRs) for smokers vs nonsmokers of 2.1 among 35- to 54-year olds and HR of 0.7 among those aged 55-69 years. Five- and 10-year mortality rates for smokers aged 35-54 years were 7.0% and 14.2%, compared with 3.3% and 10.0% for nonsmokers, respectively (χ(2) = 5.53, df = 1, P = .019). Cardiac causes were identified in 43% of deaths in smokers but only 19% of deaths in nonsmokers (P < .006). For those aged 35-54 years, the odds of cardiac related death was increased by 12 fold in smokers relative to nonsmokers (HR = 12.4, χ(2) = 12.0, df = 1, P = .0005). Among people aged 35-54 years, those smoking greater than one pack daily have a significantly increased total mortality risk (HR = 2.7) vs nonsmokers. Cigarette smoking, particularly in people aged 35-54 years, contributes to an increased risk of death. Greater smoking severity significantly increases this risk. Smoking cessation in people with schizophrenia deserves significant attention.