Healthcare utilization in patients with first-time implantable cardioverter defibrillators (data from the WEBCARE study)

Background Knowledge of the level of healthcare utilization (HCU) and the predictors of high HCU use in patients with an implantable cardioverter defibrillator (ICD) is lacking. We examined the level of HCU and predictors associated with increased HCU in first‐time ICD patients, using a prospective study design. Methods ICD patients (N = 201) completed a set of questionnaires at baseline and 3, 6, and 12 months after inclusion. A hierarchical multiple linear regression with three models was performed to examine predictors of HCU.ResultsHCU was highest between baseline and 3 months postimplantation and gradually decreased during 12 months follow‐up. During the first year postimplantation, only depression (β = 0.342, P = 0.002) was a significant predictor. Between baseline and 3 months follow‐up, younger age (β = −0.220, P < 0.01), New York Heart Association class III/IV (β = 0.705, P = 0.01), and secondary indication (β = 0.148, P = 0.05) were independent predictors for increased HCU. Between 3 and 6 months follow‐up, younger age (β = −0.151, P = 0.05) and depression (β = 0.370, P < 0.001) predicted increased HCU. Between 6 and 12 months only depression (β = 0.355, P = 0.001) remained a significant predictor.  Conclusions Depression was an important predictor of increased HCU in ICD patients in the first year postimplantation, particularly after 3 months postimplantation. Identifying patients who need additional care and provide this on time might better meet patients’ needs and lower future HCU

A new neuropsychological instrument measuring effects of age and drugs on fitness to drive: development, reliability, and validity of MedDrive

Background: Current guidelines underline the limitations of existing instruments to assess fitness to drive and the poor adaptability of batteries of neuropsychological tests in primary care settings. Aims: To provide a free, reliable, transparent computer based instrument capable of detecting effects of age or drugs on visual processing and cognitive functions. Methods: Relying on systematic reviews of neuropsychological tests and driving performances, we conceived four new computed tasks measuring: visual processing (Task1), movement attention shift (Task2), executive response, alerting and orientation gain (Task3), and spatial memory (Task4). We then planned five studies to test MedDrive's reliability and validity. Study-1 defined instructions and learning functions collecting data from 105 senior drivers attending an automobile club course. Study-2 assessed concurrent validity for detecting minor cognitive impairment (MCI) against useful field of view (UFOV) on 120 new senior drivers. Study-3 collected data from 200 healthy drivers aged 20-90 to model age related normal cognitive decline. Study-4 measured MedDrive's reliability having 21 healthy volunteers repeat tests five times. Study-5 tested MedDrive's responsiveness to alcohol in a randomised, double-blinded, placebo, crossover, dose-response validation trial including 20 young healthy volunteers. Results: Instructions were well understood and accepted by all senior drivers. Measures of visual processing (Task1) showed better performances than the UFOV in detecting MCI (ROC 0.770 vs. 0.620; p=0.048). MedDrive was capable of explaining 43.4% of changes occurring with natural cognitive decline. In young healthy drivers, learning effects became negligible from the third session onwards for all tasks except for dual tasking (ICC=0.769). All measures except alerting and orientation gain were affected by blood alcohol concentrations. Finally, MedDrive was able to explain 29.3% of potential causes of swerving on the driving simulator. Discussion and conclusions: MedDrive reveals improved performances compared to existing computed neuropsychological tasks. It shows promising results both for clinical and research purposes

Alcohol policy changes and 22-year trends in individual alcohol consumption in a Swiss adult population: a 1993-2014 cross-sectional population-based study.

Evidence on the impact of legislative changes on individual alcohol consumption is limited. Using an observational study design, we assessed trends in individual alcohol consumption of a Swiss adult population following the public policy changes that took place between 1993 and 2014, while considering individual characteristics and secular trends. Cross-sectional study. Swiss general adult population. Data from 18 963 participants were collected between 1993 and 2014 (aged 18-75 years). We used data from the 'Bus Santé' study, an annual health survey conducted in random samples of the adult population in the State of Geneva, Switzerland. Individual alcohol intake was assessed using a validated food frequency questionnaire. Individual characteristics including education were self-reported. 7 policy changes (6 about alcohol and 1 about tobacco) that occurred between 1993 and 2014 defined 6 different periods. We predicted alcohol intake using quantile regression with multivariate analysis for each period adjusting for participants' characteristics and tested significance periods. Sensitivity analysis was performed including drinkers only, the 10th centile of highest drinkers and smoker's status. Between 1993 and 2014, participants' individual alcohol intake decreased from 7.1 to 5.4 g/day (24% reduction, p&lt;0.001). Men decreased their alcohol intake by 34% compared with 22% for women (p&lt;0.001). The decrease in alcohol intake remained significant when considering drinkers only (28% decrease, p&lt;0.001) and the 10th centile highest drinkers (24% decrease, p&lt;0.001). Consumption of all alcoholic beverages decreased between 1993 and 2014 except for the moderate consumption of beer, which increased. After adjustment for participants' characteristics and secular trends, no independent association between alcohol legislative changes and individual alcohol intake was found. Between 1993 and 2014, alcohol consumption decreased in the Swiss adult population independently of policy changes

Estimation of Muscle Mass in the Integrated Assessment of Patients on Hemodialysis

Assessment of muscle mass (MM) or its proxies, lean tissue mass (LTM) or fat-free mass (FFM), is an integral part of the diagnosis of protein-energy wasting (PEW) and sarcopenia in patients on hemodialysis (HD). Both sarcopenia and PEW are related to a loss of functionality and also increased morbidity and mortality in this patient population. However, loss of MM is a part of a wider spectrum, including inflammation and fluid overload. As both sarcopenia and PEW are amendable to treatment, estimation of MM regularly is therefore of major clinical relevance. Whereas, computer-assisted tomography (CT) or dual-energy X-ray absorptiometry (DXA) is considered a reference method, it is unsuitable as a method for routine clinical monitoring. In this review, different bedside methods to estimate MM or its proxies in patients on HD will be discussed, with emphasis on biochemical methods, simplified creatinine index (SCI), bioimpedance spectroscopy (BIS), and muscle ultrasound (US). Body composition parameters of all methods are related to the outcome and appear relevant in clinical practice. The US is the only parameter by which muscle dimensions are measured. BIS and SCI are also dependent on either theoretical assumptions or the use of population-specific regression equations. Potential caveats of the methods are that SCI can be influenced by residual renal function, BIS can be influenced by fluid overload, although the latter may be circumvented by the use of a three-compartment model, and that muscle US reflects regional and not whole body MM. In conclusion, both SCI and BIS as well as muscle US are all valuable methods that can be applied for bedside nutritional assessment in patients on HD and appear suitable for routine follow-up. The choice for either method depends on local preferences. However, estimation of MM or its proxies should always be part of a multidimensional assessment of the patient followed by a personalized treatment strategy

Importance of molecular cell biology investigations in human medicine in the story of the Hutchinson-Gilford progeria syndrome

Ranged among laminopathies, Hutchinson–Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke. In the lecture I shall overview the importance of molecular cell biology investigations that led to the discovery of the basic mechanism standing behind this rare syndrome. The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene. At this position, cytosine is substituted for thymine so that a cryptic splice site within the precursor mRNA for lamin A is generated. This results in a production of abnormal lamin A, termed progerin, its presence in cells having a deleterious dominant effect. Depending on the cell type and tissue, progerin induces a pleiotropy of defects that vary in different tissues. The present endeavour how to challenge this terrible disease will be also mentioned

Etanercept for steroid-refractory acute graft-versus-host disease

Background: Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic stem cell transplantation (alloSCT). High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. No standard second-line regimen has been established. Different options have been reported, including anti-TNFα antibodies. Methods: We retrospectively reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated with etanercept at our institution. Patients were transplanted for a hematological malignancy and received either a myeloablative or a non-myeloablative conditioning regimen. Prophylaxis of GVHD consisted of cyclosporin A and mycophenolic acid. Results: Acute GVHD was diagnosed at a median of 61 days post-transplantation. All patients had grade III aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after initiation of first-line therapy. Overall response rate was 53%, with CR in 3 patients and PR in 5 patients. Median overall survival after initiation of treatment with etanercept was 66 days (range 5–267) for the entire group. Median overall survival was 99 days (range 47–267 days) for responders and 17 days (range 5–66 days) for non-responders (p<0.01). Nevertheless, all patients died. Causes of death were progressive GVHD in 7 patients (47%), infection in 6 patients (40%), cardiac death in 1 patient (6.7%) and relapse in 1 patient (6,7%). Conclusion: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients

Phloem-specific resistance in Brassica oleracea against the whitefly Aleyrodes proletella

The cabbage whitefly [Aleyrodes proletella L. (Hemiptera: Aleyrodidae)] is becoming a serious pest in Brassica oleracea L. (Brassicaceae) crops. However, almost nothing is known about the interaction of this insect with its host plants. Previous studies have shown differences in the natural occurrence of adults, eggs, and nymphs on the closely related B. oleracea cultivars Christmas Drumhead and Riviera grown in the field. In this study, we aimed to identify the nature of these differences and to gain insight into the resistance mechanisms against A. proletella. We used no-choice experiments on field- and greenhouse-grown plants to show that the differences between the two cultivars are mainly based on antibiosis (traits that reduce herbivore performance) and not on antixenosis (traits that deter herbivory). This was further supported by laboratory choice experiments that indicated little or no discrimination between the two cultivars based on plant volatiles. We showed that resistance is dependent on plant age, that is, resistance increased during plant development, and is mainly independent of environmental factors. Analysis of probing behaviour revealed that the resistance trait affects A. proletella at the phloem level and that morphological differences between the two cultivars are most likely not involved. We suggest that compounds present in the phloem reduce sap ingestion by the whitefly and that this explains the observed resistanc

A rare missense mutation in <i>GJB3</i> (Cx31G45E) is associated with a unique cellular phenotype resulting in necrotic cell death

Erythrokeratodermia variabilis et progressiva (EKV-P) is caused by mutations in either the GJB3 (Cx31) or GJB4 genes (Cx30.3). We identified a rare GJB3 missense mutation, c.134G>A (p.G45E), in two unrelated patients and investigated its cellular characteristics. Expression of Cx31G45E-GFP caused previously undescribed changes within HeLa cells and HaCaT cells, a model human keratinocyte cell line. Cx31WT-GFP localised to the plasma membrane, but expression of Cx31G45E-GFP caused vacuolar expansion of the endoplasmic reticulum (ER), the mutant protein accumulated within the ER membrane and disassembly of the microtubular network occurred. No ER stress responses were evoked. Cx31WT-myc-myc-6xHis and Cx31G45E-GFP co-immunoprecipitated, indicative of heteromeric interaction, but co-expression with Cx31WT-mCherry, Cx26 or Cx30.3 did not mitigate the phenotype. Cx31 and Cx31G45E both co-immunoprecipitated with Cx43, indicating the ability to form heteromeric connexons. WT-Cx31 and Cx43 assembled into large gap junction plaques at points of cell-to-cell contact; Cx31G45E restricted the ability of Cx43 to reach the plasma membrane in both HaCaT cells and HeLa cells stably expressing Cx43 where the proteins strongly co-localised with the vacolourised ER. Cell viability assays identified an increase in cell death in cells expressing Cx31G45E-GFP, which FACS analysis determined was necrotic. Blocking connexin channel function with 18α-glycyrrhetinic acid did not completely rescue necrosis or prevent propidium iodide uptake, suggesting that expression of Cx31G45E-GFP damages the cellular membrane independent of its channel function. Our data suggest that entrapment of Cx43 and necrotic cell death in the epidermis could underlie the EKV skin phenotype

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

Spread of Hepatitis C Virus among European Injection Drug Users Infected with HIV: A Phylogenetic Analysis

To describe the spread of hepatitis C virus (HCV) among HCV/human immunodeficiency virus (HIV)-coinfected injection drug users (IDUs), the molecular epidemiology of HCV was studied among 108 IDUs from 7 European countries. Phylogenetic analysis based on the NS5B region showed great sequence variation of HCV within each country and no clear phylogenetic clustering by geographic region. The most prevalent subtypes were 1a and 3a, but the percentage of genotype 4 was also relatively high, ranging from 7% in northern Europe to 24% in southern Europe. Genotype 4 consisted mainly of subtype 4d and has entered the majority of the IDU populations studied. The significantly lower evolutionary distances within subtype 4d suggest that this subtype may have entered the European IDU population relatively recently. In conclusion, HCV exchange between European IDU populations has occurred on a large scale, and, overall, country-specific clustering for HCV was less than that shown for HI