Association between high-risk extracranial carotid plaque and covert brain infarctions and cerebral microbleeds.

PURPOSE: Covert brain infarctions (CBIs) and cerebral microbleeds (CMBs) represent subclinical sequelae of ischemic and hemorrhagic cerebral small vessel disease, respectively. In addition to thromboembolic stroke, carotid atherosclerosis has been associated with downstream vascular brain injury, including inflammation and small vessel disease. The specific plaque features responsible for this are unknown. We aimed to determine the association of specific vulnerable carotid plaque features to CBIs and CMBs to better understand the relation of large and small vessel disease in a single-center retrospective observational study. METHODS: Intraplaque hemorrhage (IPH) and plaque ulceration were recorded on carotid MRA and total, cortical, and lacunar CBIs and CMBs were recorded on brain MR in 349 patients (698 carotid arteries). Multivariable Poisson regression was performed to relate plaque features to CBIs and CMBs. Within-subject analysis in those with unilateral IPH and ulceration was performed with Poisson regression. RESULTS: Both IPH and plaque ulceration were associated with total CBI (prevalence ratios (PR) 3.33, 95% CI: 2.16-5.15 and 1.91, 95% CI: 1.21-3.00, respectively), after adjusting for stenosis, demographic, and vascular risk factors. In subjects with unilateral IPH, PR was 2.83, 95% CI: 1.76-4.55, for CBI in the ipsilateral hemisphere after adjusting for stenosis. Among those with unilateral ulceration, PR was 1.82, 95% CI: 1.18-2.81, for total CBI ipsilateral to ulceration after adjusting for stenosis. No statistically significant association was seen with CMBs. CONCLUSION: Both IPH and plaque ulceration are associated with total, cortical, and lacunar type CBIs but not CMBs suggesting that advanced atherosclerosis contributes predominantly to ischemic markers of subclinical vascular injury.

His bundle pacing shows similar ventricular electrical activation as sinus: selective and nonselective His pacing indistinguishable.

His bundle pacing utilizes the His-Purkinje system to produce more physiological activation compared with traditional pacing therapies, but differences in electrical activation between pacing techniques are not yet quantified in terms of activation pattern. Furthermore, clinicians distinguish between selective and nonselective His pacing, but measurable differences in electrical activation remain to be seen. Hearts isolated from seven dogs were perfused using the Langendorff method. Electrograms were recorded using two 64-electrode basket catheters in the ventricles and a 128-electrode sock situated around the ventricles during sinus rhythm (right atrial pacing), right ventricular (RV) pacing, biventricular cardiac resynchronization therapy (biV-CRT), selective His pacing (selective capture of the His bundle), and nonselective His pacing (capture of nearby myocardium and His bundle). Activation maps were generated from these electrograms. Total activation time (TAT) was measured from the activation maps, and QRS duration was measured from a one-lead pseudo-ECG. Results showed that TAT, QRS duration, and activation sequence were most similar between sinus, selective, and nonselective His pacing. Bland-Altman analyses showed highest levels of similarity between all combinations of sinus, selective, and nonselective His pacing. RV and biV-CRT activation patterns were distinct from sinus and had significantly longer TAT and QRS duration. Cumulative activation graphs were most similar between sinus, selective, and nonselective His pacing. In conclusion, selective pacing and nonselective His bundle pacing are more similar to sinus compared with RV and biV-CRT pacing. Furthermore, selective pacing and nonselective His bundle pacing are not significantly different electrically.NEW & NOTEWORTHY Our high-density epicardial and endocardial electrical mapping study demonstrated that selective pacing and nonselective His bundle pacing are more electrically similar to sinus rhythm compared with right ventricular and biventricular cardiac resynchronization therapy pacing. Furthermore, small differences between selective and nonselective His bundle pacing, specifically a wider QRS in nonselective His pacing, do not translate into significant differences in the global activation pattern.

A clinical counseling tool predicting supernumerary embryos after a fresh IVF cycle.

PURPOSE: To identify factors predictive of having supernumerary embryos in a fresh IVF cycle and create a prediction model for clinical counseling. METHODS: We utilized a multivariable Poisson regression to identify predictive factors and then entered these into a logistic regression model, calculating a risk index for each significant variable. The final model was tested using a receiver operating characteristic curve. RESULTS: A total of 60,616 fresh transfer cycles were reported to the Society for Assisted Reproductive Technology in 2014. Of these, 47.17% produced supernumerary embryos. A multivariate Poisson regression identified factors predictive of having supernumerary embryos, with age and AMH being the most predictive. Clinical prediction models were developed with acceptable and excellent discrimination. 23.5% of our cohort did not achieve a live birth following their fresh transfer and had excess embryos cryopreserved for future attempts. CONCLUSION: Our study suggests that in a minority of fresh IVF cycles in the USA, the fresh transfer is not successful, and there are excess embryos cryopreserved for future use. The likelihood of excess embryos beyond those that would be transferred can be predicted with satisfactory precision prior to initiation of the cycle and with improved precision after fresh embryo transfer. Providing patients with a realistic estimate of their chances of having excess embryos at an initial IVF consult especially those with suspected poor prognosis can be beneficial in determining whether to proceed with multiple embryo banking cycles as opposed to proceeding with a fresh transfer, and whether to opt for an enhanced embryo selection technique such as preimplantation genetic testing for aneuploidy (PGT-A).

Aging impairs mouse skeletal muscle macrophage polarization and muscle-specific abundance during recovery from disuse.

Impaired recovery of aged muscle following a disuse event is an unresolved issue facing the older adult population. Although investigations in young animals have suggested that rapid regrowth of skeletal muscle following a disuse event entails a coordinated involvement of skeletal muscle macrophages, this phenomenon has not yet been thoroughly tested as an explanation for impaired muscle recovery in aging. To examine this hypothesis, young (4-5 mo) and old (24-26 mo) male mice were examined as controls following 2 wk of hindlimb unloading (HU) and following 4 (RL4) and 7 (RL7) days of reloading after HU. Muscles were harvested to assess muscle weight, myofiber-specifc cross-sectional area, and skeletal muscle macrophages via immunofluorescence. Flow cytometry was used on gastrocnemius and soleus muscle (at RL4) single-cell suspensions to immunophenotype skeletal muscle macrophages. Our data demonstrated impaired muscle regrowth in aged compared with young mice following disuse, which was characterized by divergent muscle macrophage polarization patterns and muscle-specifc macrophage abundance. During reloading, young mice exhibited the classical increase in M1-like (MHC II+CD206-) macrophages that preceeded the increase in percentage of M2-like macrophages (MHC II-CD206+); however, old mice did not demonstrate this pattern. Also, at RL4, the soleus demonstrated reduced macrophage abundance with aging. Together, these data suggest that dysregulated macrophage phenotype patterns in aged muscle during recovery from disuse may be related to impaired muscle growth. Further investigation is needed to determine whether the dysregulated macrophage response in the old during regrowth from disuse is related to a reduced ability to recruit or activate specific immune cells.

Intraoperative Transesophageal Echocardiography and Right Ventricular Failure After Left Ventricular Assist Device Implantation.

OBJECTIVE: To determine whether intraoperative measures of right ventricular (RV) function using transesophageal echocardiography are associated with subsequent RV failure after left ventricular assist device (LVAD) implantation. DESIGN: Retrospective, nonrandomized, observational study. SETTING: Single tertiary-level, university-affiliated hospital. PARTICIPANTS: The study comprised 100 patients with systolic heart failure undergoing elective LVAD implantation. INTERVENTIONS: Transesophageal echocardiographic images before and after cardiopulmonary bypass were analyzed to quantify RV function using tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (S'), fractional area change (FAC), RV global longitudinal strain, and RV free wall strain. A chart review was performed to determine which patients subsequently developed RV failure (right ventricular assist device placement or prolonged inotrope requirement ≥14 days). MEASUREMENTS AND MAIN RESULTS: Nineteen patients (19%) subsequently developed RV failure. Postbypass FAC was the only measure of RV function that distinguished between the RV failure and non-RV failure groups (21.2% v 26.5%; p = 0.04). The sensitivity, specificity, and area under the curve of an abnormal RV FAC (<35%) for RV failure after LVAD implantation were 84%, 20%, and 0.52, respectively. No other intraoperative measure of RV function was associated with subsequent RV failure. RV failure increased ventilator time, intensive care unit and hospital length of stay, and mortality. CONCLUSION: Intraoperative measures of RV function such as tricuspid annular plane systolic excursion, tricuspid annular systolic velocity, and RV strain were not associated with RV failure after LVAD implantation. Decreased postbypass FAC was significantly associated with RV failure but showed poor discrimination.

Understanding Depressive Symptoms and Psychosocial Stressors on Twitter: A Corpus-Based Study.

BACKGROUND: With a lifetime prevalence of 16.2%, major depressive disorder is the fifth biggest contributor to the disease burden in the United States. OBJECTIVE: The aim of this study, building on previous work qualitatively analyzing depression-related Twitter data, was to describe the development of a comprehensive annotation scheme (ie, coding scheme) for manually annotating Twitter data with Diagnostic and Statistical Manual of Mental Disorders, Edition 5 (DSM 5) major depressive symptoms (eg, depressed mood, weight change, psychomotor agitation, or retardation) and Diagnostic and Statistical Manual of Mental Disorders, Edition IV (DSM-IV) psychosocial stressors (eg, educational problems, problems with primary support group, housing problems). METHODS: Using this annotation scheme, we developed an annotated corpus, Depressive Symptom and Psychosocial Stressors Acquired Depression, the SAD corpus, consisting of 9300 tweets randomly sampled from the Twitter application programming interface (API) using depression-related keywords (eg, depressed, gloomy, grief). An analysis of our annotated corpus yielded several key results. RESULTS: First, 72.09% (6829/9473) of tweets containing relevant keywords were nonindicative of depressive symptoms (eg, "we're in for a new economic depression"). Second, the most prevalent symptoms in our dataset were depressed mood and fatigue or loss of energy. Third, less than 2% of tweets contained more than one depression related category (eg, diminished ability to think or concentrate, depressed mood). Finally, we found very high positive correlations between some depression-related symptoms in our annotated dataset (eg, fatigue or loss of energy and educational problems; educational problems and diminished ability to think). CONCLUSIONS: We successfully developed an annotation scheme and an annotated corpus, the SAD corpus, consisting of 9300 tweets randomly-selected from the Twitter application programming interface using depression-related keywords. Our analyses suggest that keyword queries alone might not be suitable for public health monitoring because context can change the meaning of keyword in a statement. However, postprocessing approaches could be useful for reducing the noise and improving the signal needed to detect depression symptoms using social media.

Changes in Oral Anticoagulant Treatment Rates in Atrial Fibrillation before and after the Introduction of Direct Oral Anticoagulants.

BACKGROUND: Direct oral anticoagulants (DOACs) have the potential to improve stroke prevention among atrial fibrillation (AF) patients. We sought to determine if oral anticoagulation (OAC) treatment rates have increased since the approval of DOACs. METHODS: We identified 6,688 patients with AF at an academic medical center from January 2008 to June 2015. We examined OAC prescription rates over time and according to CHA2DS2VASc score using multivariable Poisson regression models, with an interaction term between risk score and year of AF diagnosis. RESULTS: Among 6,688 AF patients, 78% had CHA2DS2VASc scores ≥2, 51.6% of whom received an OAC prescription within 90 days of diagnosis. The OAC prescription rate was 47.8% in the pre-DOAC era and peaked at 56.4% in 2014. Relative to the pre-DOAC era, prescription rates increased in 2012 and leveled off thereafter. The prescription rate for the highest risk group was 58.5%, compared with 45.0% in patients with a CHA2DS2VASc score of 2 (p < 0.01). In the adjusted analysis, prescription rates were higher for the higher risk group (adjusted relative risk 1.24 for CHA2DS2VASc score 7-9 vs. 2, 95% CI 1.09-1.40). CONCLUSIONS: OAC treatment rates have increased since DOAC introduction, but substantial treatment gaps remain, specifically among the higher risk patients.

Assessing Pictograph Recognition: A Comparison of Crowdsourcing and Traditional Survey Approaches.

BACKGROUND: Compared to traditional methods of participant recruitment, online crowdsourcing platforms provide a fast and low-cost alternative. Amazon Mechanical Turk (MTurk) is a large and well-known crowdsourcing service. It has developed into the leading platform for crowdsourcing recruitment. OBJECTIVE: To explore the application of online crowdsourcing for health informatics research, specifically the testing of medical pictographs. METHODS: A set of pictographs created for cardiovascular hospital discharge instructions was tested for recognition. This set of illustrations (n=486) was first tested through an in-person survey in a hospital setting (n=150) and then using online MTurk participants (n=150). We analyzed these survey results to determine their comparability. RESULTS: Both the demographics and the pictograph recognition rates of online participants were different from those of the in-person participants. In the multivariable linear regression model comparing the 2 groups, the MTurk group scored significantly higher than the hospital sample after adjusting for potential demographic characteristics (adjusted mean difference 0.18, 95% CI 0.08-0.28, P<.001). The adjusted mean ratings were 2.95 (95% CI 2.89-3.02) for the in-person hospital sample and 3.14 (95% CI 3.07-3.20) for the online MTurk sample on a 4-point Likert scale (1=totally incorrect, 4=totally correct). CONCLUSIONS: The findings suggest that crowdsourcing is a viable complement to traditional in-person surveys, but it cannot replace them.

In vivo human time-exposure study of orally dosed commercial silver nanoparticles.

Human biodistribution, bioprocessing and possible toxicity of nanoscale silver receive increasing health assessment. We prospectively studied commercial 10- and 32-ppm nanoscale silver particle solutions in a single-blind, controlled, cross-over, intent-to-treat, design. Healthy subjects (n=60) underwent metabolic, blood counts, urinalysis, sputum induction, and chest and abdomen magnetic resonance imaging. Silver serum and urine content were determined. No clinically important changes in metabolic, hematologic, or urinalysis measures were identified. No morphological changes were detected in the lungs, heart or abdominal organs. No significant changes were noted in pulmonary reactive oxygen species or pro-inflammatory cytokine generation. In vivo oral exposure to these commercial nanoscale silver particle solutions does not prompt clinically important changes in human metabolic, hematologic, urine, physical findings or imaging morphology. Further study of increasing time exposure and dosing of silver nanoparticulate silver, and observation of additional organ systems are warranted to assert human toxicity thresholds. FROM THE CLINICAL EDITOR: In this study, the effects of commercially available nanoparticles were studied in healthy volunteers, concluding no detectable toxicity with the utilized comprehensive assays and tests. As the authors rightfully state, further studies are definitely warranted. Studies like this are much needed for the more widespread application of nanomedicine.

Developing 60-Day Readmission Risk Score among Home Healthcare Patients with Heart Failure.

Heart failure (HF) readmissions are common, costly, and often preventable. Despite the implementation of HF programs across clinical settings, rehospitalization is still common. Efforts to identify risk factors for 60-day rehospitalization among HF patients exist, but risk scoring has not been utilized in home healthcare. The purpose of this study was to develop a 60-day rehospitalization risk score for home care patients with HF. This study is a secondary data analysis of a retrospective cross-sectional dataset that was composed of data using the Outcome Assessment Information Set (OASIS)-C version for patients with HF. We computed the Charlson Comorbidity Index (CCI) to use as a confounder. The risk score was computed from the final logistic regression model regression coefficients. The median age was 78 years old, 45.4% were male, and 81.0% were White. We identified 10 significant risk factors including CCI score. The risk score achieved a c-statistic of 0.70 in this patient sample. This risk score could prove useful in clinical practice for guiding attention and decision-making for personalized care of patients with unrecognized or under-treated health needs.