117 research outputs found
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
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
Options for early breast cancer follow-up in primary and secondary care : a systematic review
Background
Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer.
Method
A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions.
Results
Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival.
Conclusions
Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed
A preliminary study of genetic factors that influence susceptibility to bovine tuberculosis in the British cattle herd
Associations between specific host genes and susceptibility to Mycobacterial infections such as tuberculosis have been reported in several species. Bovine tuberculosis (bTB) impacts greatly the UK cattle industry, yet genetic predispositions have yet to be identified. We therefore used a candidate gene approach to study 384 cattle of which 160 had reacted positively to an antigenic skin test (‘reactors’). Our approach was unusual in that it used microsatellite markers, embraced high breed diversity and focused particularly on detecting genes showing heterozygote advantage, a mode of action often overlooked in SNP-based studies. A panel of neutral markers was used to control for population substructure and using a general linear model-based approach we were also able to control for age. We found that substructure was surprisingly weak and identified two genomic regions that were strongly associated with reactor status, identified by markers INRA111 and BMS2753. In general the strength of association detected tended to vary depending on whether age was included in the model. At INRA111 a single genotype appears strongly protective with an overall odds ratio of 2.2, the effect being consistent across nine diverse breeds. Our results suggest that breeding strategies could be devised that would appreciably increase genetic resistance of cattle to bTB (strictly, reduce the frequency of incidence of reactors) with implications for the current debate concerning badger-culling
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
Acute success and short-term follow-up of catheter ablation of isthmus-dependent atrial flutter; a comparison of 8 mm tip radiofrequency and cryothermy catheters
Objectives: To compare the acute success and short-term follow-up of ablation of atrial flutter using 8 mm tip radiofrequency (RF) and cryocatheters. Methods: Sixty-two patients with atrial flutter were randomized to RF or cryocatheter (cryo) ablation. Right atrial angiography was performed to assess the isthmus. End point was bidirectional isthmus block on multiple criteria. A pain score was used and the analgesics were recorded. Patients were followed for at least 3 months. Results: The acute success rate for RF was 83% vs 69% for cryo (NS). Procedure times were similar (mean 144±48 min for RF, vs 158±49 min for cryo). More applications were given with RF than with cryo (26±17 vs. 18±10, p<0.05). Fluoroscopy time was longer with RF (29±15 vs. 19±12 min, p<0.02). Peak CK, CK-MB and CK-MB mass were higher, also after 24 h in the cryo group. Troponin T did not differ. Repeated transient block during application (usually with cryoablation) seemed to predict failure. Cryothermy required significantly less analgesia (p<0.01), and no use of long sheaths (p<0.005). The isthmus tended to be longer in the failed procedures (p=0.117). This was similar for both groups, as was the distribution of anatomic variations. Recurrences and complaints in the successful patients were similar for both groups, with a very low recurrence of atrial flutter after initial success. Concl
Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers-reaching the frontiers of individual risk prediction
AIMS: This study aims to improve risk stratification for primary prevention implantable cardioverter defibrillator (ICD) implantation by developing a new mutation-specific prediction model for malignant ventricular arrhythmia (VA) in phospholamban (PLN) p.Arg14del mutation carriers. The proposed model is compared to an existing PLN risk model. METHODS AND RESULTS: Data were collected from PLN p.Arg14del mutation carriers with no history of malignant VA at baseline, identified between 2009 and 2020. Malignant VA was defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. A prediction model was developed using Cox regression. The study cohort consisted of 679 PLN p.Arg14del mutation carriers, with a minority of index patients (17%) and male sex (43%), and a median age of 42 years [interquartile range (IQR) 27–55]. During a median follow-up of 4.3 years (IQR 1.7–7.4), 72 (10.6%) carriers experienced malignant VA. Significant predictors were left ventricular ejection fraction, premature ventricular contraction count/24 h, amount of negative T waves, and presence of low-voltage electrocardiogram. The multivariable model had an excellent discriminative ability {C-statistic 0.83 [95% confidence interval (CI) 0.78–0.88]}. Applying the existing PLN risk model to the complete cohort yielded a C-statistic of 0.68 (95% CI 0.61–0.75). CONCLUSION: This new mutation-specific prediction model for individual VA risk in PLN p.Arg14del mutation carriers is superior to the existing PLN risk model, suggesting that risk prediction using mutation-specific phenotypic features can improve accuracy compared to a more generic approach
Quantitative Trait Loci Associated with the Immune Response to a Bovine Respiratory Syncytial Virus Vaccine
Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501) which was genotyped for 165 microsatellite markers (covering all autosomes) to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV) specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination. Regions of the bovine genome which influenced the immune response induced by BRSV vaccination were identified, as well as regions associated with the clearance of maternally derived BRSV specific antibodies. Significant positive correlations were detected within traits across time, with negative correlations between the pre- and post-vaccination time points. The whole genome scan identified 27 Quantitative Trait Loci (QTL) on 13 autosomes. Many QTL were associated with the Thymus Helper 1 linked IgG2 response, especially at week 2 following vaccination. However the most significant QTL, which reached 5% genome-wide significance, was on BTA 17 for IgG1, also 2 weeks following vaccination. All animals had declining maternally derived BRSV specific antibodies prior to vaccination and the levels of BRSV specific antibody prior to vaccination were found to be under polygenic control with several QTL detected
Pre-Absorbed Immunoproteomics: A Novel Method for the Detection of Streptococcus suis Surface Proteins
Streptococcus suis serotype 2 (SS2) is a zoonotic pathogen that can cause infections in pigs and humans. Bacterial surface proteins are often investigated as potential vaccine candidates and biomarkers of virulence. In this study, a novel method for identifying bacterial surface proteins is presented, which combines immunoproteomic and immunoserologic techniques. Critical to the success of this new method is an improved procedure for generating two-dimensional electrophoresis gel profiles of S. suis proteins. The S. suis surface proteins identified in this study include muramidase-released protein precursor (MRP) and an ABC transporter protein, while MRP is thought to be one of the main virulence factors in SS2 located on the bacterial surface. Herein, we demonstrate that the ABC transporter protein can bind to HEp-2 cells, which strongly suggests that this protein is located on the bacterial cell surface and may be involved in pathogenesis. An immunofluorescence assay confirmed that the ABC transporter is localized to the bacterial outer surface. This new method may prove to be a useful tool for identifying surface proteins, and aid in the development of new vaccine subunits and disease diagnostics
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