Age-related differences in the effect of psychological distress on mortality:Type D personality in younger versus older patients with cardiac arrhythmias

Background. Mixed findings in biobehavioral research on heart disease may partly be attributed to age-related differences in the prognostic value of psychological distress. This study sought to test the hypothesis that Type D (distressed) personality contributes to an increased mortality risk following implantable cardioverter defibrillator (ICD) treatment in younger patients but not in older patients. Methods. The Type D Scale (DS14) was used to assess general psychological distress in 455 younger (≤70 y,. Cardiac resynchronization therapy (CRT), but not Type D personality, was associated with increased mortality in older patients. Among younger patients, however, Type D personality was associated with an adjusted hazard ratio = 1.91 (95% CI 1.09–3.34) and 2.26 (95% CI 1.16–4.41) for all-cause and cardiac mortality; other predictors were increasing age, CRT, appropriate shocks, ACE-inhibitors, and smoking. Conclusion. Type D personality was independently associated with all-cause and cardiac mortality in younger ICD patients but not in older patients. Cardiovascular research needs to further explore age-related differences in psychosocial risk

Prognostic importance of distressed (Type D) personality and shocks in patients with an implantable cardioverter defibrillator

AbstractBackgroundClinical trials have shown the benefit of implantable cardioverter defibrillator (ICD) treatment. In this study, we examined the importance of chronic psychological distress and device shocks among ICD patients seen in clinical practice.MethodsThis prospective follow-up study included 589 patients with an ICD (mean age=62.6±10.1years; 81% men). At baseline, vulnerability for chronic psychological distress was measured by the 14-item Type D (distressed) personality scale. Cox regression models of all-cause and cardiac death were used to examine the importance of risk markers.ResultsAfter a median follow-up of 3.2years, 94 patients (16%) had died (67 cardiac death), 61 patients (10%) had experienced an appropriate shock and 28 (5%) an inappropriate shock. Inappropriate shocks were not associated with all-cause (p=0.52) or cardiac (p=0.99) death. However, appropriate shocks (HR=2.60, 95% CI 1.47–5.58, p=0.001) and Type D personality (HR=1.85, 95% CI 1.12–3.05, p=0.015) were independent predictors of all-cause mortality, adjusting for age, sex, left ventricular ejection fraction, cardiac resynchronization therapy (CRT), secondary indication, history of coronary artery disease, medication and diabetes. Type D personality and appropriate shocks also independently predicted an increased risk of cardiac death. Other independent predictors of poor prognosis were older age, treatment with CRT and diabetes.ConclusionVulnerability to chronic psychological distress, as defined by the Type D construct, had incremental prognostic value above and beyond clinical characteristics and ICD shocks. Physicians should be aware of chronic psychological distress and device shocks as markers of an increased mortality risk in ICD patients seen in daily clinical practice

Candesartan Mediated Amelioration of Cisplatin-Induced Testicular Damage Is Associated with Alterations in Expression Patterns of Nephrin and Podocin

Nephrin and podocin are known to be closely related to the pharmacological effects of angiotensin-II receptor blocker (ARB). The objectives of this study were to investigate the role of nephrin and podocin using cisplatin-induced testicular damage and to evaluate the effect of ARB. At first, we evaluated the effects of cisplatin either alone or in combination with ARB candesartan on changes in expression patterns of nephrin and podocin in the rat testes. We then conducted in vitro studies to investigate the effects of angiotensin using cultured Sertoli cells, line TM4. As a result, the expression of nephrin and podocin was shown to localize around the basal membrane of seminiferous tubules. Treatment with cisplatin resulted in a marked decrease in the expression of nephrin and podocin and induced a shift of both proteins from linear to granular expression patterns, accompanying the increased apoptotic index in the testes; these changes were partially restored by the additional administration of candesartan. In vitro studies with TM4 revealed the angiotensin-II mediated expression changes of nephrin and podocin. These findings suggest that candesartan can prevent cisplatin-induced testicular damage by regulating expression patterns of the nephrin-podocin complex in the testes

A Snu114-GTP-Prp8 module forms a relay station for efficient splicing in yeast

The single G protein of the spliceosome, Snu114, has been proposed to facilitate splicing as a molecular motor or as a regulatory G protein. However, available structures of spliceosomal complexes show Snu114 in the same GTP-bound state, and presently no Snu114 GTPase-regulatory protein is known. We determined a crystal structure of Snu114 with a Snu114-binding region of the Prp8 protein, in which Snu114 again adopts the same GTP-bound conformation seen in spliceosomes. Snu114 and the Snu114-Prp8 complex co-purified with endogenous GTP. Snu114 exhibited weak, intrinsic GTPase activity that was abolished by the Prp8 Snu114-binding region. Exchange of GTP-contacting residues in Snu114, or of Prp8 residues lining the Snu114 GTP-binding pocket, led to temperature-sensitive yeast growth and affected the same set of splicing events in vivo. Consistent with dynamic Snu114-mediated protein interactions during splicing, our results suggest that the Snu114-GTP-Prp8 module serves as a relay station during spliceosome activation and disassembly, but that GTPase activity may be dispensable for splicing

E-Health to manage distress in patients with an implantable cardioverter-defibrillator: Primary results of the WEBCARE trial

Objective: The Web-based distress management program for patients with an implantable cardioverter-defibrillator (ICD; WEBCARE) was developed to mitigate distress and enhance health-related quality of life in ICD patients. This study investigated the treatment effectiveness at 3-month follow-up for generic and disease-specific outcome measures. Methods: Consecutive patients implanted with a first-time ICD from six hospitals in the Netherlands were randomized to either the "WEBCARE" or the "usual care" group. Patients in the WEBCARE group received a 12-week fixed, six-lesson behavioral treatment based on the problem-solving principles of cognitive behavioral therapy. Results: Two hundred eighty-nine patients (85% response rate) were randomized. The prevalence of anxiety and depression ranged between 11% and 30% and 13% and 21%, respectively. No significant intervention effects were observed for anxiety (β = 0.35; p = .32), depression (β = -0.01; p = .98) or health-related quality of life (Mental Component Scale: β = 0.19; p = .86; Physical Component Scale: β = 0.58; p = .60) at 3 months, with effect sizes (Cohen d) being small (range, 0.06-0.13). There were also no significant group differences as measured with the disease-specific measures device acceptance (β = -0.37; p = .82), shock anxiety (β = 0.21; p = .70), and ICD-related concerns (β = -0.08; p = .90). No differences between treatment completers and noncompleters were observed on any of the measures. Conclusions: In this Web-based intervention trial, no significant intervention effects on anxiety, depression, health-related quality of life, device acceptance, shock anxiety, or ICD-related concerns were observed. A more patient tailored approach targeting the needs of different subsets of ICD patients may be warranted. Trial registration: clinicaltrials.gov. Identifier: NCT00895700

Rationale and design of the Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESiA) trial.

BACKGROUND: Device-detected subclinical atrial fibrillation (AF) refers to infrequent, short-lasting, asymptomatic AF that is detected only with long-term continuous monitoring. Subclinical AF is common and associated with an increased risk of stroke; however, the risk of stroke with subclinical AF is lower than for clinical AF, and very few patients with subclinical AF alone have been included in large AF anticoagulation trials. The net benefit of anticoagulation in patients with subclinical AF is unknown. DESIGN: ARTESiA is a prospective, multicenter, double-blind, randomized controlled trial, recruiting patients with subclinical AF detected by an implanted pacemaker, defibrillator, or cardiac monitor, and who have additional risk factors for stroke. Patients with clinical AF documented by surface electrocardiogram will be excluded from the study. Participants will be randomized to receive either apixaban (according to standard AF dosing) or aspirin 81mg daily. The primary outcome is the composite of stroke, transient ischemic attack with diffusion-weighted magnetic resonance imaging evidence of cerebral infarction, and systemic embolism. Approximately 4,000 patients will be enrolled from around 230 clinical sites, with an anticipated mean follow-up of 36months until 248 adjudicated primary outcome events have occurred. SUMMARY: ARTESiA will determine whether oral anticoagulation therapy with apixaban compared with aspirin reduces the risk of stroke or systemic embolism in patients with subclinical AF and additional risk factors

Combining EPR spectroscopy and X ray crystallography to elucidate the structure and dynamics of conformationally constrained spin labels in T4 lysozyme single crystals

Electron paramagnetic resonance (EPR) spectroscopy in combination with site-directed spin labeling is used to investigate the structure and dynamics of conformationally constrained spin labels in T4 lysozyme single crystals. Within a single crystal, the oriented ensemble of spin bearing moieties results in a strong angle dependence of the EPR spectra. A quantitative description of the EPR spectra requires the determination of the unit cell orientation with respect to the sample tube and the orientation of the spin bearing moieties within the crystal lattice. Angle dependent EPR spectra were analyzed by line shape simulations using the stochastic Liouville equation approach developed by Freed and co-workers and an effective Hamiltonian approach. The gain in spectral information obtained from the EPR spectra of single crystalline samples taken at different frequencies, namely the X-band and Q-band, allows us to discriminate between motional models describing the spectra of isotropic solutions similarly well. In addition, it is shown that the angle dependent single crystal spectra allow us to identify two spin label rotamers with very similar side chain dynamics. These results demonstrate the utility of single crystal EPR spectroscopy in combination with spectral line shape simulation techniques to extract valuable dynamic information not readily available from the analysis of isotropic systems. In addition, it will be shown that the loss of electron density in high resolution diffraction experiments at room temperature does not allow us to conclude that there is significant structural disorder in the system

Personality traits, ventricular tachyarrhythmias, and mortality in patients with an implantable cardioverter defibrillator: 6 years follow-up of the WEBCARE cohort

Objective: Risk stratification within the ICD population warrants the examining of the role of protective- and risk factors. Current study examines the association between Type D personality, pessimism, and optimism and risk of ventricular tachyarrhythmias (VTa's) and mortality in patients with a first-time ICD 6 years post implantation. Methods: A total of 221 first-implant ICD patients completed questionnaires on optimism and pessimism (Life Orientation Test) and Type D personality (Type D scale DS14) 10 to 14 days after implantation. VTa's and all-cause mortality 6 years post implant comprised the study endpoints. Results: Ninety (40.7%) patients had experienced VTa's and 37 (16.7%) patients died, 12 (5.4%) due to a cardiac cause. Adjusted logistic regression analysis showed that pessimism was significantly associated with increased risk of VTa's (OR = 1.09; 95% CI = 1.00–1.19; p =.05). Type D personality (OR = 1.05; 95% CI = 0.47–2.32; p =.91) and optimism (OR = 1.00; 95% CI = 0.90–1.12; p =.98) were not associated with VTa's. None of the personality types were associated with mortality. Conclusion: Pessimism was associated with VTa's but not with mortality. No significant association with either of the endpoints was observed for Type D personality and optimism. Future research should focus on the coexistent psychosocial factors that possibly lead to adverse cardiac prognosis in this patient population

Text-mining in electronic healthcare records can be used as efficient tool for screening and data collection in cardiovascular trials: a multicenter validation study

Objective: This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of an international trial. Study Design and Setting: In three medical centers with different EHR vendors, EHR-based text-mining was used to automatically screen patients for trial eligibility and extract baseline data on nineteen characteristics. First, the yield of screening with automated EHR text-mining search was compared with manual screening by research personnel. Second, the accuracy of extracted baseline data by EHR text mining was compared to manual data entry by research personnel. Results: Of the 92,466 patients visiting the out-patient cardiology departments, 568 (0.6%) were enrolled in the trial during its recruitment period using manual screening methods. Automated EHR data screening of all patients showed that the number of patients needed to screen could be reduced by 73,863 (79.9%). The remaining 18,603 (20.1%) contained 458 of the actual participants (82.4% of participants). In trial participants, automated EHR text-mining missed a median of 2.8% (Interquartile range [IQR] across all variables 0.4e8.5%) of all data points compared to manually collected data. The overall accuracy of automatically extracted data was 88.0% (IQR 84.7e92.8%). Conclusion: Automatically extracting data from EHRs using text-mining can be used to identify trial participants and to collect baseline informatio

Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity

PurposeTo evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma (POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss.DesignCross-sectional study.ParticipantsOne hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older.MethodsSubjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system.Main Outcome MeasuresPupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7–14 log photons/cm2 per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography [HRT]; Heidelberg Engineering, Heidelberg, Germany).ResultsThe pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r = −0.44; P = 0.005) as well as HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve head parameters.ConclusionsIn glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma