Hospital utilisation and the costs associated with complications of ICD implantation in a contemporary primary prevention cohort

Introduction: Implantation of an implantable cardioverter defibrillator (ICD) is standard care for primary prevention of sudden cardiac death. However, ICD-related complications are increasing as the population of ICD recipients grows. Methods: ICD-related complications in a national DO-IT Registry cohort of 1442 primary prevention ICD patients were assessed in terms of additional use of hospital care resources and costs. Results: During a median follow-up of 28.7 months (IQR 25.2–33.7) one or more complications occurred in 13.5% of patients. A complication resulted in a surgical intervention in 53% of cases and required on average 3.65 additional hospital days. The additional hospital costs were €6,876 per complication or €8,110 per patient, to which clinical re-interventions and additional hospital days contributed most. Per category of complications, infections required most hospital utilisation and were most expensive at an average of €22,892. The mean costs were €5,800 for lead-related complications, €2,291 for pocket-related complications and €5,619 for complications due to other causes. We estimate that the total yearly incidence-based costs in the Netherlands for hospital management of ICD-related complications following ICD implantation for primary prevention are €2.7 million. Conclusion: Complications following ICD implantation are related to a substantial additional need for hospital resources. When performing cost-effectiveness analyses of ICD implantation, including the costs associated with complications, one should be aware that real-world complication rates may deviate from trial data. Considering the economic implications, strategies to reduce the incidence of complications are encouraged.</p

Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases

Critical cancer pathways often cannot be targeted because of limited efficiency crossing cell membranes. Here we report the development of a Salmonella-based intracellular delivery system to address this challenge. We engineer genetic circuits that (1) activate the regulator flhDC to drive invasion and (2) induce lysis to release proteins into tumor cells. Released protein drugs diffuse from Salmonella containing vacuoles into the cellular cytoplasm where they interact with their therapeutic targets. Control of invasion with flhDC increases delivery over 500 times. The autonomous triggering of lysis after invasion makes the platform self-limiting and prevents drug release in healthy organs. Bacterial delivery of constitutively active caspase-3 blocks the growth of hepatocellular carcinoma and lung metastases, and increases survival in mice. This success in targeted killing of cancer cells provides critical evidence that this approach will be applicable to a wide range of protein drugs for the treatment of solid tumors

Dutch Outcome in Implantable Cardioverter-Defibrillator Therapy:Implantable Cardioverter-Defibrillator-Related Complications in a Contemporary Primary Prevention Cohort

Background One third of primary prevention implantable cardioverter-defibrillator patients receive appropriate therapy, but all remain at risk of defibrillator complications. Information on these complications in contemporary cohorts is limited. This study assessed complications and their risk factors after defibrillator implantation in a Dutch nationwide prospective registry cohort and forecasts the potential reduction in complications under distinct scenarios of updated indication criteria. Methods and Results Complications in a prospective multicenter registry cohort of 1442 primary implantable cardioverter-defibrillator implant patients were classified as major or minor. The potential for reducing complications was derived from a newly developed prediction model of appropriate therapy to identify patients with a low probability of benefitting from the implantable cardioverter-defibrillator. During a follow-up of 2.2 years (interquartile range, 2.0-2.6 years), 228 complications occurred in 195 patients (13.6%), with 113 patients (7.8%) experiencing at least one major complication. Most common ones were lead related (n=93) and infection (n=18). Minor complications occurred in 6.8% of patients, with lead-related (n=47) and pocket-related (n=40) complications as the most prevailing ones. A surgical reintervention or additional hospitalization was required in 53% or 61% of complications, respectively. Complications were strongly associated with device type. Application of stricter implant indication results in a comparable proportional reduction of (major) complications. Conclusions One in 13 patients experiences at least one major implantable cardioverter-defibrillator-related complication, and many patients undergo a surgical reintervention. Complications are related to defibrillator implantations, and these should be discussed with the patient. Stricter implant indication criteria and careful selection of device type implanted may have significant clinical and financial benefits

Immunopathogenesis and Immune Modulation of Venezuelan Equine Encephalitis Virus-Induced Disease in the Mouse

AbstractThe course of Venezuelan equine encephalitis (VEE) disease in immunodeficient and immunologically normal mice was compared to define the role of the immune system in this disease process. Immunocompetent mice infected with VEE exhibited a biphasic illness characterized by an early self-limiting lymphoid phase and a fatal CNS phase. The lymphoid phase of the illness was characterized by extensive viral replication within spleen, thymus, Peyer's patches, and lymph nodes, was accompanied by a high-titered serum viremia, and resolved with the production of VEE-specific IgM class antibody at 72 h postinfection (p.i.). Immunocompetent animals survived an average of 6.8 ± 1.2 days before succumbing to fulminant encephalitis. In contrast, SCID mice infected with VEE showed a persistent replication of virus throughout all organs tested beginning at 24 h p.i. VEE-infected SCID mice exhibited a severe spongiform encephalopathy with 100% mortality and an average survival time of 8.9 ± 0.9 days. These studies indicated that the characteristic organ tropism of VEE in the mouse is due in large part to an early anti-viral state, the establishment of which is dependent upon the presence of an intact immune system. Finally, the CNS pathology in a VEE-infected mouse had a significant immunologic component. However, in contrast to other neurovirulent alphaviruses, VEE was directly cytopathic for the cells of the CNS, even in the absence of an immune response

Dutch outcome in implantable cardioverter-defibrillator therapy (DO-IT)

Background Implantable cardioverter-defibrillators (ICDs) are widely used for the prevention of sudden cardiac death. At present, both clinical benefit and cost-effectiveness of ICD therapy in primary prevention patients are topics of discussion, as only a minority of these patients will eventually receive appropriate ICD therapy. Methods/design The DO-IT Registry is a nationwide prospective cohort with a target enrolment of 1,500 primary prevention ICD patients with reduced left ventricular function in a setting of structural heart disease. The primary outcome measures are death and appropriate ICD therapy for ventricular tachyarrhythmias. Secondary outcome measures are inappropriate ICD therapy, death of any cause, hospitalisation for ICD related complications and for cardiovascular reasons. As of December 2016, data on demographic, clinical, and ICD characteristics of 1,468 patients have been collected. Follow-up will continue up to 24 months after inclusion of the last patient. During follow-up, clinical and ICD data are collected based on the normal follow-up of these patients, assuming ICD interrogations take place every six months and clinical follow-up i

When people co-occur with good or bad events: graded effects of relational qualifiers on evaluative conditioning

Studies on evaluative conditioning show that a change in liking can occur whenever stimuli are paired. Such instances of attitude change are known to depend on the type of relation established between stimuli (e.g., “Bob is a friend of Mike” vs. “Bob is an enemy of Mike”). Research has so far only compared assimilative and contrastive relational qualifiers (e.g., friend vs. enemy). For the first time, we compared the effect of non-oppositional qualifiers on attitude change in a EC procedure (e.g., “Bob causes Positive Outcomes” vs. “Bob predicts Positive Outcomes”). Differential effects of non-oppositional relational qualifiers were observed on explicit and implicit evaluations. We discuss the implications of our findings for attitude research, theories of attitude change, and for optimizing evaluative conditioning for changing attitudes in applied settings

Effectiveness of a cognitive behavioural intervention for patients with undifferentiated somatoform disorder: results from the CIPRUS cluster randomized controlled trial in primary care

Objective: To examine the effectiveness of a cognitive behavioural intervention delivered by mental health nurse practitioners (MHNPs) to patients with undifferentiated somatoform disorder (USD), compared to usual care. Methods: We conducted a cluster randomized trial among primary care patients with USD comparing the intervention to usual care. The intervention consisted of six sessions with the MHNP. Primary outcome was physical functioning (RAND-36 physical component summary score). Secondary outcomes were the RAND-36 mental component summary score and the eight subscales; anxiety and depression (Hospital Anxiety and Depression Scale) and somatic symptom severity (Patient Health Questionnaire-15). Outcomes were assessed at baseline, 2, 4 and 12 months. We analysed data using linear mixed models by intention-to-treat, and investigated effect modifiers. Results: Compared to usual care (n=87), the intervention group (n=111) showed an improvement in physical functioning (mean difference 2.24 [95% CI 0.51; 3.97]; p=.011), a decrease in limitations due to physical problems (mean difference 10.82 [95% CI 2.14; 19.49]; p.=0.015) and in pain (mean difference 5.08 [95% CI 0.58; 9.57]; p=.027), over 12 months. However effect sizes were small and less clinically relevant than expected. We found no differences for anxiety, depression and somatic symptom severity. Effects were larger and clinically relevant for patients with more recent symptoms and fewer physical diseases. Conclusion: The cognitive behavioural intervention was effective in improving pain and physical functioning components of patients' health. It was particularly suitable for patients with symptoms that had been present for a limited number of years and with few comorbid physical diseases. Trial registration: The trial is registered in the Dutch Trial Registry, www.trialregister.nl, under NTR4686

Achttien Vlaamse auteurs gebundeld

Modern and Contemporary Studie