Publications

BACKGROUND

Myocardial fibrosis imaging using late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) has been validated as a quantitative predictive marker for response to medical, surgical, and device therapy. To date, all such studies have examined conventional, non-phase corrected magnitude images.  However, contemporary practice has rapdily adopted phase-corrected image reconstruction. We sought to investigate the existence of any systematic bias between threshold-based scar quantification performed on conventional magnitude inversion recovery (MIR) and matched phase sensitive inversion recovery (PSIR) images.

METHODS

In 80 patients with confirmed ischemic (N = 40), or non-ischemic (n = 40) myocardial fibrosis, and also in a healthy control cohort (N = 40) without fibrosis, myocardial late enhancement was quantified using a Signal Threshold Versus Reference Myocardium technique (STRM) at ≥2, ≥3, and ≥5 SD threshold, and also using the Full Width at Half Maximal (FWHM) technique. This was performed on both MIR and PSIR images and values compared using linear regression and Bland-Altman analyses.

RESULTS

Linear regression analysis demonstrated excellent correlation for scar volumes between MIR and PSIR images at all three STRM signal thresholds for the ischemic (N = 40, r = 0.96, 0.95, 0.88 at 2, 3, and 5 SD, p < 0.0001 for all regressions), and non ischemic (N = 40, r = 0.86, 0.89, 0.90 at 2, 3, and 5 SD, p < 0.0001 for all regressions) cohorts. FWHM analysis demonstrated good correlation in the ischemic population (N = 40, r = 0.83, p < 0.0001). Bland-Altman analysis demonstrated a systematic bias with MIR images showing higher values than PSIR for ischemic (3.3 %, 3.9 % and 4.9 % at 2, 3, and 5 SD, respectively), and non-ischemic (9.7 %, 7.4 % and 4.1 % at ≥2, ≥3, and ≥5 SD thresholds, respectively) cohorts. Background myocardial signal measured in the control population demonstrated a similar bias of 4.4 %, 2.6 % and 0.7 % of the LV volume at 2, 3 and 5 SD thresholds, respectively. The bias observed using FWHM analysis was -6.9 %.

CONCLUSIONS

Scar quantification using phase corrected (PSIR) images achieves values highly correlated to those obtained on non-corrected (MIR) images. However, a systematic bias exists that appears exaggerated in non-ischemic cohorts. Such bias should be considered when comparing or translating knowledge between MIR- and PSIR-based imaging.

Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to 'hallmark' processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age.

BACKGROUND

Guidelines recommend cardiac rehabilitation after acute myocardial infarction, yet little is known about the impact of cardiac rehabilitation on medication adherence and clinical outcomes among contemporary older adults. The optimal number of cardiac rehabilitation sessions is not clear.

METHODS

We linked patients 65years or older enrolled in the Acute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines (ACTION Registry-GWTG) from January 2007 to December 2010 to Medicare longitudinal claims data to obtain 1 year follow-up.

RESULTS

A total of 11,862 patients participated in cardiac rehabilitation after acute myocardial infarction, attending a median number of 26 sessions. Patients attending ≥26 sessions were more likely to be male, had lesser prevalence of comorbid conditions and prior revascularization, and were more likely to present with ST-segment elevation myocardial infarction, compared with patients attending 1 to 25 sessions. Among patients with Medicare Part D prescription coverage, increasing number of cardiac rehabilitation sessions was associated with improvement in adherence to secondary prevention medications such as P2Y12 inhibitors and β-blockers. Each 5-session increase in participation was associated with lower mortality (adjusted hazard ratio [HR] 0.87, 95% CI 0.83-0.92) and lower overall risk of major adverse cardiac event (adjusted HR 0.69, 95% CI 0.65-0.73) and death/readmission (adjusted HR 0.79, 95% CI 0.76-0.83).

CONCLUSIONS

In this older patient population, number of cardiac rehabilitation sessions attended was associated with improved medication adherence and lower downstream cardiovascular risk in a dose-response relationship. This provides support for the continued use of cardiac rehabilitation for older adults and encourages efforts to maximize attendance.

OBJECTIVE

Non-medical prescription opioid use is a growing public health concern. Social media is an emerging tool to understand health attitudes, beliefs, and behaviors.

METHODS

We retrieved a sample of publicly available Twitter messages in early 2014, using common opioid medication names and slang search terms. We used content analysis to code messages by user, context of message (personal vs general experiences), and key content themes.

RESULTS

We reviewed 540 messages, of which 375 (69%) messages were related to opioid behaviors. Of these, 316 (84%) originated from individual user accounts; 125 messages expressed personal experience with opioids. The majority of personal messages referenced using opioids to obtain a "high", use for sleep, or other non-intended use (87,70%). General attitudes regarding opioid use included positive sentiment (52, 27%), comments on others peoples opioid use (57, 30%), and messages containing public health information or links (48, 25%).

CONCLUSIONS

In a sample of social media messages mentioning opioid medications, the most common theme amongst English users related to various forms of opioid misuse. Social media can provide insights into the types of misuse of opioids that might aid public health efforts to reduce non-medical opioid use.

BACKGROUND

Higher left ventricular mass (LV) strongly predicts cardiovascular mortality in hemodialysis patients. Although several parameters of preload and afterload have been associated with higher LV mass, whether these parameters independently predict LV mass, remains unclear.

METHODS

This study examined a cohort of 391 adults with incident hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study. The main exposures were systolic and diastolic blood pressure (BP), pulse pressure, arterial stiffness by pulse wave velocity (PWV), volume status estimated by pulmonary pressures using echocardiogram and intradialytic weight gain. The primary outcome was baseline left ventricular mass index (LVMI).

RESULTS

Each systolic, diastolic blood, and pulse pressure measurement was significantly associated with LVMI by linear regression regardless of dialysis unit BP or non-dialysis day BP measurements. Adjusting for cardiovascular confounders, every 10 mmHg increase in systolic or diastolic BP was significantly associated with higher LVMI (SBP β = 7.26, 95 % CI: 4.30, 10.23; DBP β = 10.05, 95 % CI: 5.06, 15.04), and increased pulse pressure was also associated with higher LVMI (β = 0.71, 95 % CI: 0.29, 1.13). Intradialytic weight gain was also associated with higher LVMI but attenuated effects after adjustment (β = 3.25, 95 % CI: 0.67, 5.83). PWV and pulmonary pressures were not associated with LVMI after multivariable adjustment (β = 0.19, 95 % CI: -1.14, 1.79; and β = 0.10, 95 % CI: -0.51, 0.70, respectively). Simultaneously adjusting for all main exposures demonstrated that higher BP was independently associated with higher LVMI (SBP β = 5.64, 95 % CI: 2.78, 8.49; DBP β = 7.29, 95 % CI: 2.26, 12.31, for every 10 mmHg increase in BP).

CONCLUSIONS

Among a younger and incident hemodialysis population, higher systolic, diastolic, or pulse pressure, regardless of timing with dialysis, is most associated with higher LV mass. Future studies should consider the use of various BP measures in examining the impact of BP on LVM and cardiovascular disease. Findings from such studies could suggest that high BP should be more aggressively treated to promote LVH regression in incident hemodialysis patients.

Because two-thirds of patients with Major Depressive Disorder do not achieve remission with their first antidepressant, we designed a trial of three "next-step" strategies: switching to another antidepressant (bupropion-SR) or augmenting the current antidepressant with either another antidepressant (bupropion-SR) or with an atypical antipsychotic (aripiprazole). The study will compare 12-week remission rates and, among those who have at least a partial response, relapse rates for up to 6 months of additional treatment. We review seven key efficacy/effectiveness design decisions in this mixed "efficacy-effectiveness" trial.