Long-term Results of a 12-Week Comprehensive Ambulatory Cardiac Rehabilitation Program

PURPOSE: To evaluate the long-term outcome of a 12-week outpatient cardiac rehabilitation (CR) program. METHODS: In a prospective single-center interventional cohort study, 201 consecutive patients (133 patients after acute coronary syndrome, 32 patients after heart surgery, and 36 patients with heart failure) attending a 12-week comprehensive outpatient CR program were evaluated for exercise capacity, cardiovascular risk factors (CvRFs), and quality of life at entry, end, and 1.4 years after completion of the program (followup). RESULTS: Physical exercise capacity improved significantly from program entry to program end and remained at this level at followup (P ≤ .006). CvRFs at followup were significantly reduced with regard to smoking prevalence and blood lipids (P < .001). At program end and followup, MacNew heart disease–specific emotional, physical, and social quality of life were improved significantly compared with those at program entry (P < .001). Use of cardioprotective medication remained equally high over the entire study period. However, significantly fewer patients reached blood pressure (<140/90 mm Hg, P = .034) and body mass index (<30 kg/m2, P = .017) goals at followup than at program end. CONCLUSION: The 12-week comprehensive outpatient CR program was successful at reducing important CvRFs long-term.

Measuring mindfulness: first steps towards the development of a comprehensive mindfulness scale

The present study describes the development of and results obtained from the first version of a new mindfulness scale: the Comprehensive Inventory of Mindfulness Experiences beta (CHIME-β). The aim of the present analysis was to investigate two relevant open questions in mindfulness assessment: (1) the coverage of aspects of mindfulness and (2) the type of interrelationships among these aspects. A review of the aspects of mindfulness assessed by eight currently available mindfulness questionnaires led to the identification of nine aspects of mindfulness. The CHIME-β was constructed in order to cover each of these aspects in a balanced way. Initially, principal component and confirmatory factor analyses, as well as reliability and validity analyses, were performed in the entire sample (n = 313) of individuals from the general population and mindfulness-based stress reduction (MBSR) groups. The factor structure that emerged from this analysis was further investigated in meditation-trained individuals (n = 144) who had just completed an MBSR intervention. Results suggested a four-factor structure underlying the nine aspects proposed. The relationship between these mindfulness factors appears to be influenced by the degree of meditation experience. In fact, the mindfulness factors showed a greater interconnectedness among mediation-trained participants. Finally, data suggest that a non-avoidant stance plays a central role in mindfulness, while the capacity to put inner experiences into words may be related to mindfulness rather than a component of the construct.

Comprehensive MicroRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma

BACKGROUND Follicular variant of papillary thyroid carcinoma (FVPTC) shares features of papillary (PTC) and follicular (FTC) thyroid carcinomas on a clinical, morphological, and genetic level. MicroRNA (miRNA) deregulation was extensively studied in PTCs and FTCs. However, very limited information is available for FVPTC. The aim of this study was to assess miRNA expression in FVPTC with the most comprehensive miRNA array panel and to correlate it with the clinicopathological data. METHODS Forty-four papillary thyroid carcinomas (17 FVPTC, 27 classic PTC) and eight normal thyroid tissue samples were analyzed for expression of 748 miRNAs using Human Microarray Assays on the ABI 7900 platform (Life Technologies, Carlsbad, CA). In addition, an independent set of 61 tumor and normal samples was studied for expression of novel miRNA markers detected in this study. RESULTS Overall, the miRNA expression profile demonstrated similar trends between FVPTC and classic PTC. Fourteen miRNAs were deregulated in FVPTC with a fold change of more than five (up/down), including miRNAs known to be upregulated in PTC (miR-146b-3p, -146-5p, -221, -222 and miR-222-5p) and novel miRNAs (miR-375, -551b, 181-2-3p, 99b-3p). However, the levels of miRNA expression were different between these tumor types and some miRNAs were uniquely dysregulated in FVPTC allowing separation of these tumors on the unsupervised hierarchical clustering analysis. Upregulation of novel miR-375 was confirmed in a large independent set of follicular cell derived neoplasms and benign nodules and demonstrated specific upregulation for PTC. Two miRNAs (miR-181a-2-3p, miR-99b-3p) were associated with an adverse outcome in FVPTC patients by a Kaplan-Meier (p < 0.05) and multivariate Cox regression analysis (p < 0.05). CONCLUSIONS Despite high similarity in miRNA expression between FVPTC and classic PTC, several miRNAs were uniquely expressed in each tumor type, supporting their histopathologic differences. Highly upregulated miRNA identified in this study (miR-375) can serve as a novel marker of papillary thyroid carcinoma, and miR-181a-2-3p and miR-99b-3p can predict relapse-free survival in patients with FVPTC thus potentially providing important diagnostic and predictive value.

Is the Atlantic subpolar gyre bistable in comprehensive coupled climate models?

The Atlantic subpolar gyre (SPG) is one of the main drivers of decadal climate variability in the North Atlantic. Here we analyze its dynamics in pre-industrial control simulations of 19 different comprehensive coupled climate models. The analysis is based on a recently proposed description of the SPG dynamics that found the circulation to be potentially bistable due to a positive feedback mechanism including salt transport and enhanced deep convection in the SPG center. We employ a statistical method to identify multiple equilibria in time series that are subject to strong noise and analyze composite fields to assess whether the bistability results from the hypothesized feedback mechanism. Because noise dominates the time series in most models, multiple circulation modes can unambiguously be detected in only six models. Four of these six models confirm that the intensification is caused by the positive feedback mechanism.

Effect of comprehensive cardiac rehabilitation after heart valve surgery (CopenHeartVR): study protocol for a randomised clinical trial

Background Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery. Methods A randomised clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients, 1:1 intervention to control group, using central randomisation, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise, and a psycho-educational intervention comprising five consultations. Primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. Secondary outcome is self-assessed mental health measured by the standardised questionnaire Short Form 36. Also, long-term healthcare utilisation and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. Discussion The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015).

From school to work: A comprehensive model of work-related motivation in the transition to working life.

Motivation is a core concept to understand work related outcomes and vocational pursuits. However, existing research mostly focused on specific aspects of motivation, such as goals or self-efficacy beliefs, while falling short of adequately addressing more complex and integrative notions of motivation. Advancing the current state of research, we draw from Motivational Systems Theory and a model of proactive motivation to propose a comprehensive model of work-related motivation. Specifically, we define motivation as a system of mutually related factors consisting of goals, emotions, and personal agency beliefs, comprised by capability beliefs and context evaluations. Adapting this model of motivation to the school-to-work transition, we postulate that this motivational system is affected by different social, personal, and environmental variables, for example social support, the presence of role-models, personality traits, and scholastic achievement. We further expect that students with more autonomous work-related goals, expectations of more positive emotional experiences in their future working life, fewer perceived barriers to their career development, and higher work-related self-efficacy beliefs would be more successful in their transition from school to work. We also propose that goal-directed engagement acts as a partial mediator in the relationship between motivation and a successful transition. Finally, we hypothesize that work-related motivation while in school will have meaningful effects on positive outcomes while in vocational training, as represented by more work engagement, higher career commitment, job satisfaction, and lower intentions to quit training. In sum, we advance the point that the adaptation of a broader concept of work-related motivation in the school-to-work transition would result in more powerful predictions of success in this transition and would enhance scientific research and interventions in career development and counselling practice.

Konstruktion und erste Validierung eines Fragebogens zur umfassenden Erfassung von Achtsamkeit: Das Comprehensive Inventory of Mindfulness Experiences

In der vorliegenden Arbeit werden Entwicklung und Validierung eines Fragebogens zur umfassenden Erfassung der Achtsamkeit, des Comprehensive Inventory of Mindfulness Experiences (CHIME), beschrieben. An einer Allgemeinbevölkerungs-Stichprobe (N = 298) und einer Stichprobe von TeilnehmerInnen an MBSR-Kursen (N = 161) wurde die Faktorenstruktur des CHIME ermittelt und seine Reliabilität und Validität geprüft. Faktorenanalytische Verfahren ergaben eine achtfaktorielle Struktur. Die Struktur wurde in einer zusätzlichen konfirmatorischen Stichprobe (N = 202) überprüft. Der Fragebogen sowie seine Unterskalen weisen gute Reliabilitätswerte auf (interne Konsistenz und Retest-Reliabilität). Analysen zur Messinvarianz der einzelnen Items über Gruppen, die sich bezüglich Meditationserfahrung, Alter, Geschlecht und Symptombelastung unterschieden, zeigten keine systematischen Unterschiede im Verständnis der Items. Die Kennwerte zur Konstrukt-, Kriterium-, und inkrementellen Validität sowie zur Veränderungssensitivität waren alle mindestens zufriedenstellend. Mit dem CHIME steht somit ein Fragebogen mit guten psychometrischen Eigenschaften zur Selbsteinschätzung der Achtsamkeit zur Verfügung. Der CHIME basiert auf allen in den aktuellen Instrumenten enthaltenen Aspekten des Achtsamkeitskonstrukts.

Significance of social cognitive remediation therapy within a comprehensive treatment concept

Objectives: The final goal in the successful treatment of schizophrenia patients is defined in improved functional recovery. Thus the integration of social cognitive tasks within a comprehensive treatment concept should offer significant advantages in generalization and transfer of therapy effects. Recent therapy outcome research supports these advantages. Empirical modeling identified social cognition as a mediating factor between neurocognition and functional recovery. Regarding this, we first developed the Integrated Psychological Therapy Program (IPT). It consists of 5 subprograms and combines interventions on neurocognition, social cognition, and social competence. As a further development of the cognitive part of IPT we developed the Integrated Neurocognitive Therapy (INT), which focuses on all social and neurocognitive domains defined by MATRICS. Methods: The aim was to investigate whether the application of the complete IPT is superior in comparison to the use of single IPT subprograms. Data were based on 37 independent IPT studies including a total sample of 1692 schizophrenia patients. Additionally, the proximal outcome in cognitive domains as well as in more distal outcome areas was investigated in an international RCT on INT including 169 schizophrenia outpatients. Results: All IPT subprogram variations obtained significant effects in proximal outcome. Each subprogram domain reached the largest effects in the targeted area. With regard to distal outcomes, combinations of subprograms showed a significant reduction of negative symptoms and an improvement in not targeted areas of functioning. This strongly supports vertical generalization effects to other functional domains. Regarding INT, results support efficacy compared to TAU in various cognitive domains, in psychosocial functioning and symptoms after therapy and at 1-year-follow-up. Conclusion: Results support evidence for the efficacy of longer lasting integrated therapy. The success of these treatment concepts is strongly based on successful therapy of social cognitive functions.

Die umfassende Erfassung von Achtsamkeit zur Erforschung achtsamkeitsbasierter Interventionen bei psychischen Störungen – Das Comprehensive Inventory of Mindfulness Experiences (CHIME)

Einleitung: Achtsamkeitsbasierte psychotherapeutische Interventionen haben sich in den letzten Jahren als wirksame Methoden bei der Behandlung unterschiedlichen psychischen Störungen etabliert. So konnte z.B. die Achtsamkeitsbasierte Kognitive Therapie der Depression (Mindfulness Based Cognitive Therapy, MBCT) in kontrollierten Studien eine Halbierung der Rückfallraten bei rezidivierenden Depressionen erreichen. Auch die Mindfulness Based Stress Reduction (MBSR) erwies sich in einem weiteren Bereich von Störungen als wirksam. Zur Evaluation und weiteren Entwicklung achtsamkeitsbasierter Interventionen ist eine umfassende und differenzierte Erfassung der Trait-Achtsamkeit und ihrer Veränderung im Rahmen der Behandlung von vorrangiger Bedeutung. Die bisher vorliegenden Instrumente konnte diese Anforderungen nur teilwiese erfüllen. Methode: Im vorliegenden Beitrag werden Entwicklung und Validierung eines Fragebogens zur umfassenden Erfassung der Achtsamkeit, des Comprehensive Inventory of Mindfulness Experiences (CHIME, Bergomi, Tschacher & Kupper, 2014), beschrieben. An einer Allgemeinbevölkerungs-Stichprobe (N=298) und einer Stichprobe von TeilnehmerInnen an MBSR-Gruppen (N=161) wurde die Faktorenstruktur des CHIME ermittelt und seine Reliabilität und Validität geprüft. Ergebnisse: Faktorenanalytische Verfahren ergaben eine achtfaktorielle Struktur. Der Fragebogen sowie seine Unterskalen weisen gute Reliabilitätswerte auf (interne Konsistenz und Retest-Reliabilität). Analysen zur Messinvarianz der einzelnen Items über Gruppen, die sich bezüglich Meditationserfahrung, Alter, Geschlecht und Symptombelastung unterschieden, zeigten keine systematischen Unterschiede im Verständnis der Items. Die Kennwerte zur Konstrukt-, Kriterium-, und inkrementellen Validität sowie zurVeränderungssensitivität waren alle mindestens zufriedenstellend. Mit dem CHIME steht somit ein Fragebogen mit guten psychometrischen Eigenschaften zur Selbsteinschätzung der Achtsamkeit zur Verfügung. Der CHIME basiert auf alle in den aktuellen Instrumenten enthaltenen Aspekte des Achtsamkeitskonstrukts und kann die Evaluation und weitere Entwicklung von achtsamkeitsbasierten Interventionen bei psychischen Störungen unterstützen. Referenz: Bergomi, C., Tschacher, W. & Kupper, Z. (2014). Konstruktion und erste Validierung eines Fragebogens zur umfassenden Erfassung von Achtsamkeit: Das Comprehensive Inventory of Mindfulness Experiences. Diagnostica. 60 (3) 111-125.

Construction and first validation of the comprehensive inventory of mindfulness (CHIME)

Introduction: Measuring trait mindfulness and change in mindfulness may be a crucial prerequisite for the evaluation and further development of mindfulness based interventions for the treatment of mental disorders. This endeavour is nontrivial as current measures cover varying aspects and mindfulness and may have problems regarding validity. This presentation describes the development and validation of a questionnaire for the comprehensive assessment of mindfulness: the Comprehensive Inventory of Mindfulness Experiences (CHIME). Method: The factor structure, reliability, and validity of the CHIME were established in a community sample (N = 298) and a sample of MBSR group participants (N = 161). Results: Factor-analytical procedures supported an eight-factor structure. The structure was tested in a further confirmatory sample (N = 202). The questionnaire and its subscales exhibited good reliability (internal consistency and retest-reliability). Analysis of the measurement invariance of the single items over groups differing in age, gender, meditation experience, and symptom load pointed to the absence of systematic differences in the items' semantic understanding. Parameters reflecting construct validity, criterion validity, and incremental validity as well as change sensitivity were all at least satisfactory. Conclusions: The CHIME is a self-report measure with favorable psychometric properties based on all aspects of mindfulness that are included in current mindfulness scales. This scale may be helpful in the evaluation and further development of mindfulness based interventions.

Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.

Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only parasitostatic effect of benzimidazoles in AE.

Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer-what has gone wrong? A blueprint for the way forward in biomarker studies

BACKGROUND Treatment planning of localised prostate cancer remains challenging. Besides conventional parameters, a wealth of prognostic biomarkers has been proposed so far. None of which, however, have successfully been implemented in a routine setting so far. The aim of our study was to systematically verify a set of published prognostic markers for prostate cancer. METHODS Following an in-depth PubMed search, 28 markers were selected that have been proposed as multivariate prognostic markers for primary prostate cancer. Their prognostic validity was examined in a radical prostatectomy cohort of 238 patients with a median follow-up of 60 months and biochemical progression as endpoint of the analysis. Immunohistochemical evaluation was performed using previously published cut-off values, but allowing for optimisation if necessary. Univariate and multivariate Cox regression were used to determine the prognostic value of biomarkers included in this study. RESULTS Despite the application of various cut-offs in the analysis, only four (14%) markers were verified as independently prognostic (AKT1, stromal AR, EZH2, and PSMA) for PSA relapse following radical prostatectomy. CONCLUSIONS Apparently, many immunohistochemistry-based studies on prognostic markers seem to be over-optimistic. Codes of best practice, such as the REMARK guidelines, may facilitate the performance of conclusive and transparent future studies.