Defining Major Depressive Disorder Cohorts Using the EHR: Multiple Phenotypes Based on ICD-9 Codes and Medication Orders.

BACKGROUND: Major Depressive Disorder (MDD) is one of the most common mental illnesses and a leading cause of disability worldwide. Electronic Health Records (EHR) allow researchers to conduct unprecedented large-scale observational studies investigating MDD, its disease development and its interaction with other health outcomes. While there exist methods to classify patients as clear cases or controls, given specific data requirements, there are presently no simple, generalizable, and validated methods to classify an entire patient population into varying groups of depression likelihood and severity. METHODS: We have tested a simple, pragmatic electronic phenotype algorithm that classifies patients into one of five mutually exclusive, ordinal groups, varying in depression phenotype. Using data from an integrated health system on 278,026 patients from a 10-year study period we have tested the convergent validity of these constructs using measures of external validation, including patterns of psychiatric prescriptions, symptom severity, indicators of suicidality, comorbidity, mortality, health care utilization, and polygenic risk scores for MDD. RESULTS: We found consistent patterns of increasing morbidity and/or adverse outcomes across the five groups, providing evidence for convergent validity. LIMITATIONS: The study population is from a single rural integrated health system which is predominantly white, possibly limiting its generalizability. CONCLUSION: Our study provides initial evidence that a simple algorithm, generalizable to most EHR data sets, provides categories with meaningful face and convergent validity that can be used for stratification of an entire patient population.

Right ventricular strain before and after pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Right ventricular (RV) function is significantly impaired in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Two-dimensional speckle tracking RV strain and strain rate are novel methods to assess regional RV systolic function in CTEPH patients before and after pulmonary thromboendarterectomy (PTE). Our goal was to (1) assess baseline longitudinal strain and strain rate of the basal RV free wall in CTEPH and (2) measure early changes in RV strain and strain rate after PTE. METHODS: We performed echocardiography on 30 consecutive patients with CTEPH referred for PTE with adequate pre- and post-PTE strain imaging. Strain and strain rate were assessed 6.4 ± 4.5 days before and 9.1 ± 3.9 after PTE. RESULTS: Basal RV free wall strain and time to peak strain-but not basal RV strain rate and time to peak strain rate-changed significantly after PTE. Unexpectedly, basal RV strain became less negative, from -24.3% to -18.9% after PTE (P = 0.005). Time to peak strain decreased from 356 to 287 msec after PTE (P < 0.001). Preoperatively, RV strain correlated with pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (mPAP) but this relationship was not evident postoperatively. Furthermore, the change in RV strain did not correlate with the change in mPAP or PVR. CONCLUSIONS: In patients with CTEPH, RV basal strain paradoxically became less negative (i.e., relative systolic shortening decreased) following PTE. This change in RV strain could be due to intraoperative RV ischemia and/or postoperative stunning. Thus, RV basal strain cannot be used as a surrogate marker for surgical success early after PTE.

Left ventricular strain and strain rate by 2D speckle tracking in chronic thromboembolic pulmonary hypertension before and after pulmonary thromboendarterectomy.

BACKGROUND: Echocardiographic evaluation of left ventricular (LV) strain and strain rate (SR) by 2D speckle tracking may be useful tools to assess chronic thromboembolic pulmonary hypertension (CTEPH) severity as well as response to successful pulmonary thromboendarterectomy (PTE). METHODS: We evaluated 30 patients with CTEPH before and after PTE using 2D speckle tracking measurements of LV radial and circumferential strain and SR in the short axis, and correlated the data with right heart catheterization (RHC). RESULTS: PTE resulted in a decrease in mean PA pressure (44 ± 15 to 29 ± 9 mmHg), decrease in PVR (950 ± 550 to 31 ± 160 [dyne-sec]/cm5), and an increase in cardiac output (3.9 ± 1.0 to 5.0 ± 1.0 L/min, p < 0.001 for all). Circumferential and posterior wall radial strain changed by -11% and +15% respectively (p < 0.001 for both). Circumferential SR and posterior wall radial SR changed by -7% and 6% after PTE. While the increase in posterior wall SR with PTE reached statistical significance (p = 0.04) circumferential SR did not (p = 0.07). In addition, septal radial strain and SR did not change significantly after PTE (p = 0.1 and 0.8 respectively). Linear regression analyses of circumferential and posterior wall radial strain and SR revealed little correlation between strain/SR measurements and PVR, mean PA pressure, or cardiac output. However, change in circumferential strain and change in posterior wall radial strain correlated moderately well with changes in PVR, mean PA pressure and cardiac output (r = 0.69, 0.76, and 0.51 for circumferential strain [p < 0.001 for all] and r = 0.7, 0.7, 0.45 for posterior wall radial strain [p = 0.001, 0.001, and 0.02, respectively]). CONCLUSIONS: LV circumferential and posterior wall radial strain change after relief of pulmonary arterial obstruction in patients with CTEPH, and these improvements occur rapidly. These changes in LV strain may reflect effects from improved LV diastolic filling, and may be useful non-invasive markers of successful PTE.

Effect of prehospital 12-lead electrocardiogram on activation of the cardiac catheterization laboratory and door-to-balloon time in ST-segment elevation acute myocardial infarction.

Reducing door-to-balloon (D + B) time during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction (STEMI) reduces mortality. Prehospital 12-lead electrocadiography (ECG) with cardiac catheterization laboratory (CCL) activation may reduce D + B time. Paramedic-performed ECG was initiated in the city of San Diego in January 2005 with STEMI diagnosis based on an automated computer algorithm. We undertook this study to determine the effect of prehospital CCL activation on D + B time for patients with acute STEMI brought to our institution. All data were prospectively collected for patients with STEMI including times to treatment and clinical outcomes. We evaluated 78 consecutive patients with STEMI from January 2005 to June 2006, and the study group consisted of all patients with prehospital activation of the CCL (field STEMI; n = 20). The control groups included concurrently-treated patients with STEMI during the same period who presented to the emergency department (nonfield STEMI; n = 28), and all patients with STEMI treated in the preceding year (2004) (historical STEMI; n = 30). Prehospital CCL activation significantly reduced D + B time (73 +/- 19 minutes field STEMI, 130 +/- 66 minutes nonfield STEMI, 141 +/- 49 minutes historical STEMI; p <0.001) with significant reductions in door-to-CCL and CCL-to-balloon times as well. The majority of patients with field STEMI achieved D + B times of <90 minutes (80% field STEMI, 25% nonfield STEMI, 10% historical STEMI; p <0.001). In conclusion, this study demonstrates that prehospital electrocardiographic diagnosis of STEMI with activation of the CCL markedly reduces D + B time.

Using electrocardiographic activation time and diastolic intervals to separate focal from macro-re-entrant atrial tachycardias.

OBJECTIVES: This study was designed to separate focal from atypical macro-re-entrant atrial tachycardia (AT) on the electrocardiogram (ECG). BACKGROUND: Focal AT often cannot be distinguished from macro-re-entrant AT until the time of electrophysiology study (EPS). We hypothesized that quantitative ECG metrics should separate focal AT, using its short activation relative to tachycardia cycle length (CL), from macro-re-entrant AT, whose activation should span the CL. We developed tools to accurately quantify CL and P- or F-wave duration even when overlying T waves, then prospectively applied them to patients during focal or macro-re-entrant AT ablation and compared them to the gold standard EPS diagnosis. METHODS: We studied 41 patients (27 men, 14 women) age 57 +/- 17 years. In the training group (n = 20), tachycardia P or F waves overlying T waves were identified from transitions in slope (dV/dt) relative to "expected" T waves generated from scaling of the sinus-rate T-wave. Electrocardiographic P-wave duration agreed with the duration of intra-atrial activation. Autocorrelation was used to estimate ECG atrial CL (p < 0.001). RESULTS: Compared to macro-re-entry (n = 13), focal AT (n = 7) had shorter P waves (115 +/- 31 ms vs. 227 +/- 67 ms; p < 0.001) that were smaller ratios of CL (28 +/- 7% vs. 85 +/- 21%; p < 0.001). Receiver-operating characteristic curve areas for AT were 0.92 for P(F)-wave duration and 0.99 for P(F)/CL ratio. On blinded prospective analysis (n = 21), P(F)-wave duration <160 ms identified focal (n = 7) from macro-re-entrant AT (n = 14) with 90% sensitivity and 90% specificity, and a P(F)/CL ratio <45% gave 86% sensitivity and 98% specificity. CONCLUSIONS: Quantitative ECG indexes of shorter atrial activation and longer diastolic interval separate focal from macro-re-entrant AT without diagnostic maneuvers.

Transient expression of doublecortin during adult neurogenesis.

During development of the central nervous system, expression of the microtubule binding protein doublecortin (DCX) is associated with migration of neuroblasts. In addition to this developmental role, expression of DCX remains high within certain areas of the adult mammalian brain. These areas, mainly the dentate gyrus and the lateral ventricle wall in conjunction with the rostral migratory stream and olfactory bulb, retain the capacity to generate new neurons into adulthood. Adult neurogenesis is typically detected by incorporation of bromodeoxyuridine (BrdU) into dividing cells and colabeling of BrdU-positive cells with markers for mature neurons. To elucidate whether DCX could act as an alternative indicator for adult neurogenesis, we investigated the temporal expression pattern of DCX in neurogenic regions of the adult brain. Analysis of newly generated cells showed that DCX is transiently expressed in proliferating progenitor cells and newly generated neuroblasts. As the newly generated cells began expressing mature neuronal markers, DCX immunoreactivity decreased sharply below the level of detection and remained undetectable thereafter. The transient expression pattern of DCX in neuronal committed progenitor cells/neuroblasts indicates that DCX could be developed into a suitable marker for adult neurogenesis and may provide an alternative to BrdU labeling. This assumption is further supported by our observation that the number of DCX-expressing cells in the dentate gyrus was decreased with age according to the reduction of neurogenesis in the aging dentate gyrus previously reported.