Prediction of arrhythmic events by Wedensky modulation in patients with coronary artery disease.

PRINCIPLES Prediction of arrhythmic events (AEs) has gained importance with the availability of implantable cardioverter-defibrillators (ICDs), but is still imprecise. This study evaluated the innovative Wedensky modulation index (WMI) as predictor of AEs. METHODS In this prospective cohort, 179 patients with coronary artery disease (CAD) referred for AE risk assessment underwent baseline evaluation including measurement of R-/T-wave WMI (WMI(RT)) and left ventricular ejection fraction (LVEF). Two endpoints were assessed 3 years after the baseline evaluation: sudden cardiac death or appropriate ICD event (EP1) and any cardiac death or appropriate ICD event (EP2). Associations between baseline predictors (WMI(RT) and LVEF) and endpoints were evaluated in regression models. RESULTS Only three patients were lost to follow-up. EP1 and EP2 occurred in 24 and 27 patients, respectively. WMI(RT) (odds ratio [OR] per 1 point increase for EP1 20.1, 95% confidence interval [CI] 1.8-221.4, p = 0.014, and for EP2 73.3, 95% CI 6.6-817.7, p <0.001) and LVEF (OR per 1% increase for EP1 0.94, 95% CI 0.90-0.99, p = 0.013, and for EP2 0.93, 95% CI 0.89-0.97, p = 0.002) were significantly associated with both endpoints. In bivariable regression controlled for LVEF, WMI(RT) was independently associated with EP1 (p = 0.047) and EP2 (p = 0.007). The combination of WMI(RT) ≥0.60 and LVEF ≤30% resulted in a positive predictive value of 36% for EP1 and 50% for EP2. CONCLUSIONS WMI(RT) is a significant predictor of AEs independent of LVEF and has potential to improve AE risk prediction in CAD patients. However, WMI(RT) should be evaluated in larger and independent samples before recommendations for clinical routine can be made.

Temporal trends in the systemic inflammatory response syndrome, sepsis, and medical coding of sepsis.

BACKGROUND Recent reports using administrative claims data suggest the incidence of community- and hospital-onset sepsis is increasing. Whether this reflects changing epidemiology, more effective diagnostic methods, or changes in physician documentation and medical coding practices is unclear. METHODS We performed a temporal-trend study from 2008 to 2012 using administrative claims data and patient-level clinical data of adult patients admitted to Barnes-Jewish Hospital in St. Louis, Missouri. Temporal-trend and annual percent change were estimated using regression models with autoregressive integrated moving average errors. RESULTS We analyzed 62,261 inpatient admissions during the 5-year study period. 'Any SIRS' (i.e., SIRS on a single calendar day during the hospitalization) and 'multi-day SIRS' (i.e., SIRS on 3 or more calendar days), which both use patient-level data, and medical coding for sepsis (i.e., ICD-9-CM discharge diagnosis codes 995.91, 995.92, or 785.52) were present in 35.3 %, 17.3 %, and 3.3 % of admissions, respectively. The incidence of admissions coded for sepsis increased 9.7 % (95 % CI: 6.1, 13.4) per year, while the patient data-defined events of 'any SIRS' decreased by 1.8 % (95 % CI: -3.2, -0.5) and 'multi-day SIRS' did not change significantly over the study period. Clinically-defined sepsis (defined as SIRS plus bacteremia) and severe sepsis (defined as SIRS plus hypotension and bacteremia) decreased at statistically significant rates of 5.7 % (95 % CI: -9.0, -2.4) and 8.6 % (95 % CI: -4.4, -12.6) annually. All-cause mortality, SIRS mortality, and SIRS and clinically-defined sepsis case fatality did not change significantly during the study period. Sepsis mortality, based on ICD-9-CM codes, however, increased by 8.8 % (95 % CI: 1.9, 16.2) annually. CONCLUSIONS The incidence of sepsis, defined by ICD-9-CM codes, and sepsis mortality increased steadily without a concomitant increase in SIRS or clinically-defined sepsis. Our results highlight the need to develop strategies to integrate clinical patient-level data with administrative data to draw more accurate conclusions about the epidemiology of sepsis.

High-Dose Benzodiazepine Dependence: A Qualitative Study of Patients' Perceptions on Initiation, Reasons for Use, and Obtainment

BACKGROUND High-dose benzodiazepine (BZD) dependence is associated with a wide variety of negative health consequences. Affected individuals are reported to suffer from severe mental disorders and are often unable to achieve long-term abstinence via recommended discontinuation strategies. Although it is increasingly understood that treatment interventions should take subjective experiences and beliefs into account, the perceptions of this group of individuals remain under-investigated. METHODS We conducted an exploratory qualitative study with 41 adult subjects meeting criteria for (high-dose) BZD-dependence, as defined by ICD-10. One-on-one in-depth interviews allowed for an exploration of this group's views on the reasons behind their initial and then continued use of BZDs, as well as their procurement strategies. Mayring's qualitative content analysis was used to evaluate our data. RESULTS In this sample, all participants had developed explanatory models for why they began using BZDs. We identified a multitude of reasons that we grouped into four broad categories, as explaining continued BZD use: (1) to cope with symptoms of psychological distress or mental disorder other than substance use, (2) to manage symptoms of physical or psychological discomfort associated with somatic disorder, (3) to alleviate symptoms of substance-related disorders, and (4) for recreational purposes, that is, sensation-seeking and other social reasons. Subjects often considered BZDs less dangerous than other substances and associated their use more often with harm reduction than as recreational. Specific obtainment strategies varied widely: the majority of participants oscillated between legal and illegal methods, often relying on the black market when faced with treatment termination. CONCLUSIONS Irrespective of comorbidity, participants expressed a clear preference for medically related explanatory models for their BZD use. We therefore suggest that clinicians consider patients' motives for long-term, high-dose BZD use when formulating treatment plans for this patient group, especially since it is known that individuals are more compliant with approaches they perceive to be manageable, tolerable, and effective.

Swiss Feline Cancer Registry: A Retrospective Study of the Occurrence of Tumours in Cats in Switzerland from 1965 to 2008

Cancer is one of the leading causes of death in companion animals. Information on the epidemiology of cancer is instrumental for veterinary practitioners in patient management; however, spontaneously arising tumours in companion animals also resemble those in man and can provide useful data in combating cancer. Veterinary cancer registries for cats are few in number and have often remained short-lived. This paper presents a retrospective study of tumours in cats in Switzerland from 1965 to 2008. Tumour diagnoses were coded according to topographical and morphological keys of the International Classification of Oncology for Humans (ICD-O-3). Correlations between breed, sex and age were then examined using a multiple logistic regression model. A total of 18,375 tumours were diagnosed in 51,322 cats. Of these, 14,759 (80.3%) tumours were malignant. Several breeds had significantly lower odds ratios for developing a tumour compared with European shorthair cats. The odds of a cat developing a tumour increased with age, up to the age of 16 years, and female cats had higher risk of developing a tumour compared with male cats. Skin (4,970; 27.05%) was the most frequent location for tumours, followed by connective tissue (3,498; 19.04%), unknown location (2,532; 13.78%) and female sexual organs (1,564; 8.51%). The most common tumour types were epithelial tumours (7,913; 43.06%), mesenchymal tumours (5,142; 27.98%) and lymphoid tumours (3,911; 21.28%).

Vitamin D Deficiency and Depressive Symptomatology in Psychiatric Patients Hospitalized with a Current Depressive Episode: A Factor Analytic Study.

BACKGROUND Low vitamin D levels have been associated with depressive symptoms in population-based studies and non-clinical samples as well as with clinical depression. This study aimed to examine the association of vitamin D levels with the severity and dimensions of depressive symptoms in hospitalized patients with a current episode of depression taking into account confounding variables. METHODS We investigated 380 patients (mean age 47 ± 12 years, 70% women) who were consecutively hospitalized with a main diagnosis of an ICD-10 depressive episode. All patients self-rated depressive symptom severity with the Hospital Anxiety and Depression Scale (HADS-D), the Beck Depression Inventory-II (BDI-II), and the Brief Symptom Inventory. A principal component analysis was performed with all 34 items of these questionnaires and serum levels of 25-hydroxyvitamin D3 (25-OH D) were measured. RESULTS Vitamin D deficiency (< 50 nmol/l), insufficiency (50-75 nmol/l), and sufficiency (> 75 nmol/l) were present in 55.5%, 31.8% and 12.6%, respectively, of patients. Patients with vitamin D deficiency scored higher on the HADS-D scale and on an anhedonia symptom factor than those with insufficient (p-values ≤ 0.023) or sufficient (p-values ≤ 0.008) vitamin D. Vitamin D deficient patients also scored higher on the BDI-II scale than those with sufficient vitamin D (p = 0.007); BDI-II cognitive/affective symptoms, but not somatic/affective symptoms, were higher in patients with vitamin D deficiency (p = 0.005) and insufficiency (p = 0.041) relative to those with sufficient vitamin D. Effect sizes suggested clinically relevant findings. CONCLUSIONS Low vitamin D levels are frequent in hospitalized patients with a current episode of depression. Especially 25-OH D levels < 50 nmol/l were associated with cognitive/affective depressive symptoms, and anhedonia symptoms in particular.

Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death.

The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation.

Utility of electrophysiological studies to predict arrhythmic events

AIM To evaluate the prognostic value of electrophysiological stimulation (EPS) in the risk stratification for tachyarrhythmic events and sudden cardiac death (SCD). METHODS We conducted a prospective cohort study and analyzed the long-term follow-up of 265 consecutive patients who underwent programmed ventricular stimulation at the Luzerner Kantonsspital (Lucerne, Switzerland) between October 2003 and April 2012. Patients underwent EPS for SCD risk evaluation because of structural or functional heart disease and/or electrical conduction abnormality and/or after syncope/cardiac arrest. EPS was considered abnormal, if a sustained ventricular tachycardia (VT) was inducible. The primary endpoint of the study was SCD or, in implanted patients, adequate ICD-activation. RESULTS During EPS, sustained VT was induced in 125 patients (47.2%) and non-sustained VT in 60 patients (22.6%); in 80 patients (30.2%) no arrhythmia could be induced. In our cohort, 153 patients (57.7%) underwent ICD implantation after the EPS. During follow-up (mean duration 4.8 ± 2.3 years), a primary endpoint event occurred in 49 patients (18.5%). The area under the receiver operating characteristic curve (AUROC) was 0.593 (95%CI: 0.515-0.670) for a left ventricular ejection fraction (LVEF) < 35% and 0.636 (95%CI: 0.563-0.709) for inducible sustained VT during EPS. The AUROC of EPS was higher in the subgroup of patients with LVEF ≥ 35% (0.681, 95%CI: 0.578-0.785). Cox regression analysis showed that both, sustained VT during EPS (HR: 2.26, 95%CI: 1.22-4.19, P = 0.009) and LVEF < 35% (HR: 2.00, 95%CI: 1.13-3.54, P = 0.018) were independent predictors of primary endpoint events. CONCLUSION EPS provides a benefit in risk stratification for future tachyarrhythmic events and SCD and should especially be considered in patients with LVEF ≥ 35%.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

Adjustment Disorders Are Uniquely Suited for eHealth Interventions: Concept and Case Study

Background: Adjustment disorders (also known as mental distress in response to a stressor) are among the most frequently diagnosed mental disorders in psychiatry and clinical psychology worldwide. They are also commonly diagnosed in clients engaging in deliberate self-harm and in those consulting general practitioners. However, their reputation in research-oriented mental health remains weak since they are largely underresearched. This may change when the International Statistical Classification of Diseases-11 (ICD-11) by the World Health Organization is introduced, including a new conceptualization of adjustment disorders as a stress-response disorder with positively defined core symptoms. Objective: This paper provides an overview of evidence-based interventions for adjustment disorders. Methods: We reviewed the new ICD-11 concept of adjustment disorder and discuss the the rationale and case study of an unguided self-help protocol for burglary victims with adjustment disorder, and its possible implementation as an eHealth intervention. Results: Overall, the treatment with the self-help manual reduced symptoms of adjustment disorder, namely preoccupation and failure to adapt, as well as symptoms of depression, anxiety, and stress. Conclusions: E-mental health options are considered uniquely suited for offering early intervention after the experiences of stressful life events that potentially trigger adjustment disorders.