Inclusion of Safety-Related Issues in Economic Evaluations for Seasonal Influenza Vaccines:A Systematic Review

(1) Background: Vaccines for seasonal influenza are a good preventive and cost-effective strategy. However, it is unknown if and how these economic evaluations include the adverse events following immunization (AEFI), and what the impact of such inclusion is on the health economic outcomes. (2) Methods: We searched the literature, up to January 2020, to identify economic evaluations of seasonal influenza vaccines that considered AEFIs. The review protocol was published in PROSPERO (CDR42017058523). (3) Results: A total of 52 economic evaluations considered AEFI-related parameters in their analyses, reflecting 16% of the economic evaluations on seasonal influenza vaccines in the initial study selection. Most studies used the societal perspective (64%) and evaluated vaccination of children (37%). Where considered, studies included direct medical costs of AEFIs (90%), indirect costs (27%), and disutilities/quality-adjusted life years loss due to AEFIs (37%). The majority of these studies accounted for the effects of the costs of AEFI on cost-effectiveness for Guillain–Barré syndrome. In those papers allowing cost share estimation, direct medical cost of AFEIs was less than 2% of total direct costs. (4) Conclusions: Although the overall impact of AEFIs on the cost-effectiveness outcomes was found to be low, we urge their inclusion in economic evaluations of seasonal influenza vaccines to reflect comprehensive reports for the decision makers and end-users of the vaccination strategies

Genetics in heart failure:where are we headed?

Heart failure is a complex disease with many precipitating factors. Novel insights into the genetic background of heart failure have boosted new areas of research that gave rise to the concept of genetic predisposition for heart failure. Various genetic defects and variances have been identified and subsequently linked to the onset of or progression to heart failure. Nevertheless, our understanding of the genetic basis for heart failure is incomplete because we lack knowledge of the functionality of genetic variances. We also do not understand the impact of genetic variances in noncoding DNA because of logistic problems in performing whole-genome scans and difficulties in statistical evaluation of large amounts of data generated by the genetic boom. It is expected that in the future we will be able to overcome these problems and apply the knowledge gained by genetic analyses to target and optimize treatment.</p

Goal processes &amp; self-efficacy related to psychological distress in head &amp; neck cancer patients and their partners

Purpose and objective of the research: In this cross-sectional study we used a self-regulation perspective to better understand the experience of psychological distress in head & neck (H&N) cancer patients and their partners. We examined which goals they valued and the extent to which patients and partners experience goal disturbance. Furthermore, associations were explored between goal disturbance, goal reengagement, (goal)self-efficacy, and psychological distress. Methods and sample: H&N cancer patients and their partners, recruited from the Erasmus Medical Center Rotterdam (N = 40), were interviewed and completed questionnaires, assessing the above aspects of the self-regulation theory. Key results: H&N cancer patients and their partners experienced goal disturbance from the disease. Such disturbances were in patients significantly related to more psychological distress. Higher levels of goal re-engagement were related to less psychological distress, again only significantly in patients. More self-efficacy was significantly associated with less psychological distress in both patients and partners. Conclusions: Self-regulation abilities as goal re-engagement and self-efficacy may be screened and used as target in future psychological interventions, given their potential to decrease perceived psychological distress. In view of elevated levels of goal disturbances in partners, psychological support for caring relatives in such interventions is recommended. (c) 2010 Published by Elsevier Ltd

Optimal echocardiographic assessment of myocardial dysfunction for arrhythmic risk stratification in phospholamban mutation carriers

AIMS: Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing malignant ventricular arrhythmias (VAs) and/or heart failure. Currently, left ventricular ejection fraction (LVEF) plays an important role in risk assessment for VA in these individuals. We aimed to study the incremental prognostic value of left ventricular mechanical dispersion (LVMD) by echocardiographic deformation imaging for prediction of sustained VA in PLN p.Arg14del mutation carriers. METHODS AND RESULTS: We included 243 PLN p.Arg14del mutation carriers, which were classified into three groups according to the '45/45' rule: (i) normal left ventricular (LV) function, defined as preserved LVEF ≥45% with normal LVMD ≤45 ms (n = 139), (ii) mechanical LV dysfunction, defined as preserved LVEF ≥45% with abnormal LVMD >45 ms (n = 63), and (iii) overt LV dysfunction, defined as reduced LVEF <45% (n = 41). During a median follow-up of 3.3 (interquartile range 1.8-6.0) years, sustained VA occurred in 35 individuals. The negative predictive value of having normal LV function at baseline was 99% [95% confidence interval (CI): 92-100%] for developing sustained VA. The positive predictive value of mechanical LV dysfunction was 20% (95% CI: 15-27%). Mechanical LV dysfunction was an independent predictor of sustained VA in multivariable analysis [hazard ratio adjusted for VA history: 20.48 (95% CI: 2.57-162.84)]. CONCLUSION: LVMD has incremental prognostic value on top of LVEF in PLN p.Arg14del mutation carriers, particularly in those with preserved LVEF. The '45/45' rule is a practical approach to echocardiographic risk stratification in this challenging group of patients. This approach may also have added value in other diseases where LVEF deterioration is a relative late marker of myocardial dysfunction

The value of genetic testing in the diagnosis and risk stratification of arrhythmogenic right ventricular cardiomyopathy

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by risk of malignant ventricular arrhythmias (VA). ARVC is diagnosed using an array of clinical tests in the consensus-based task force criteria (TFC), one of which is genetic testing. OBJECTIVE: To investigate the value of genetic testing in diagnosing ARVC and its relation to the occurrence of first malignant VA. METHODS: A multicenter cohort of ARVC patients was scored using the revised 2010 TFC with and without genetic criterion, analyzing any resulting loss or delay of diagnosis. Malignant VA was defined as sustained ventricular arrhythmia (≥30s duration at ≥100 bpm or requiring intervention). RESULTS: We included 402 subjects (55% male, 54% proband, 40 [27-51] years old at presentation) who were diagnosed with definite ARVC. A total of 232 (58%) subjects fulfilled genetic testing criteria. Removing the genetic criterion caused loss of diagnosis in 18 (4%) patients (11/216 [5%] probands, 7/186 [4%] relatives), and delay of diagnosis ≥30 days in 22 (5%) patients (21/216 [10%] probands, 1/186 [0.5%] relative). A first malignant VA occurred in no patients who lost diagnosis and in 3 patients (3/216 [1%] probands and no relatives) during their diagnosis delay, none fatal. Time to event analysis showed no significant difference in time from diagnosis to malignant VA between pathogenic variant carriers and non-carriers. CONCLUSION: Disregarding the genetic criterion of the TFC caused loss or delay of diagnosis in 10% (n=40/402) of ARVC patients. Malignant VA occurred in 1% (n=3/402) of cases with lost or delayed diagnosis, none fatal

Integrated Platform for Testing MEMS Mechanical Properties at the Wafer Scale by the IMaP Methodology

Extracts basic mechanical properties such as Young's modulus and cantilever curvature

Differentiation between pediatric irritable bowel syndrome and inflammatory bowel disease based on fecal scent : proof of principle study

The diagnostic work-up of pediatric irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) commonly includes invasive tests for discrimination from inflammatory bowel disease (IBD). As this carries a high burden on patients, an ongoing need exists for development of noninvasive diagnostic biomarkers for IBS and FAP-NOS. Several studies have shown microbiota alterations in IBS/FAP, which are considered to be reflected by fecal volatile organic compounds (VOCs). The object of the study was to evaluate whether pediatric IBS/FAP-NOS could be discriminated from IBD and healthy controls by fecal VOC analysis. IBS/FAP-NOS was diagnosed according to the ROME IV criteria, and de novo IBD patients and healthy controls (HCs) aged 4 to 17 years were matched on age and sex. Fecal VOCs were analyzed by means of field asymmetric ion mobility spectrometry. Fecal VOCs of 15 IBS/FAP-NOS, 30 IBD (15 ulcerative colitis, 15 Crohn's disease) patients and 30 HCs were analyzed and compared. Differentiation between IBS/FAP-NOS and IBD was feasible with high accuracy (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.88-1; P < 0.00001). IBS/FAP-NOS profiles could not be differentiated from HCs (AUC, 0.59; 95% CI, 0.41-0.77; P = 0.167), whereas IBD profiles could with high accuracy (AUC, 0.96; 95% CI, 0.93-1; P < 0.00001). Pediatric IBS/FAP-NOS could be differentiated from IBD by fecal VOC analysis with high accuracy, but not from healthy controls. The latter finding limits the potential of fecal VOCs to serve as a diagnostic biomarker for IBS/FAP-NOS. However, VOC could possibly serve as additional noninvasive biomarker to differentiate IBS/FAP-NOS from IBD

Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers

Liver transplantation is frequently associated with hyperkalemia, especially after graft reperfusion. Dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia/reperfusion injury and improves graft function, compared to conventional static cold storage (SCS). We examined the effect of DHOPE on ex situ and in vivo shifts of potassium and sodium. Potassium and sodium shifts were derived from balance measurements in a preclinical study of livers that underwent DHOPE (n = 6) or SCS alone (n = 9), followed by ex situ normothermic reperfusion. Similar measurements were performed in a clinical study of DHOPE-preserved livers (n = 10) and control livers that were transplanted after SCS only (n = 9). During DHOPE, preclinical and clinical livers released a mean of 17 +/- 2 and 34 +/- 6 mmol potassium and took up 25 +/- 9 and 24 +/- 14 mmol sodium, respectively. After subsequent normothermic reperfusion, DHOPE-preserved livers took up a mean of 19 +/- 3 mmol potassium, while controls released 8 +/- 5 mmol potassium. During liver transplantation, blood potassium levels decreased upon reperfusion of DHOPE-preserved livers while levels increased after reperfusion of SCS-preserved liver, delta potassium levels were -0.77 +/- 0.20 vs. +0.64 +/- 0.37 mmol/L, respectively (P = .002). While hyperkalemia is generally anticipated during transplantation of SCS-preserved livers, reperfusion of hypothermic machine perfused livers can lead to decreased blood potassium or even hypokalemia in the recipient

The Survival Paradox of Elderly Patients After Major Liver Resections

The objective of this study is to assess the outcome of liver resections in the elderly in a matched control analysis. From a prospective single center database of 628 patients, 132 patients were aged 60 years or over and underwent a primary major liver resection. Of these patients, 93 could be matched one-to-one with a control patient, aged less than 60 years, with the same diagnosis and the same type of liver resection. The mean age difference was 16.7 years. Patients over 60 years of age had a significantly higher American Society of Anaesthesiologists (ASA) grade. All other demographics and operative characteristics were not different. In-hospital mortality and morbidity were higher in the patients over 60 years of age (11% versus 2%, p=0.017 and 47% versus 31%, p=0.024). One-, 3-, and 5-year survival rates in the patients over 60 years of age were 81%, 58%, and 42%, respectively, compared to 90%, 59%, and 42% in the control patients (p=0.558). Unified model Cox regression analysis showed that resection margin status (hazard ratio 2.51) and ASA grade (hazard ratio 2.26), and not age, were determining factors for survival. This finding underlines the important fact that in patient selection for major liver resections, ASA grade is more important than patient age

IGF-1 is not related to long-term outcome in hyperglycemic acute coronary syndrome patients

PURPOSE: Insulin-like growth factor-1 (IGF-1) has been associated with both protective and detrimental effects on the development of ischemic heart disease. The relationship between IGF-1 levels and major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients remains unclear. This study aimed to investigate the relationship between IGF-1 admission levels in hyperglycemic ACS patients and: (1) MACE over a 5 years follow-up, (2) type 2 diabetes at discharge, and (3) post-ACS myocardial infarct size and dysfunction. METHODS: This was a post hoc analysis of the BIOMArCS-2 randomized controlled trial. From July 2008 to February 2012, 276 ACS patients with admission plasma glucose level between 140 and 288 mg/dL were included. Records of the composite of all-cause mortality and recurrent non-fatal myocardial infarction were obtained during 5 years follow-up. Venous blood samples were collected on admission. IGF-1 was measured batchwise after study completion. Oral glucose tolerance test was performed to diagnose type 2 diabetes, whereas infarct size and left ventricular function were assessed by myocardial perfusion scintigraphy (MPS) imaging, 6 weeks post-ACS. RESULTS: Cumulative incidence of MACE was 24% at 5 years follow-up. IGF-1 was not independently associated with MACE (HR:1.00 (95%CI:0.99–1.00), p = 0.29). Seventy-eight patients (28%) had type 2 diabetes at discharge, and the highest quartile of IGF-1 levels was associated with the lowest incidence of diabetes (HR:0.40 (95%CI:0.17–0.95), p = 0.037). IGF-1 levels were not associated with post-ACS myocardial infarct size and dysfunction. CONCLUSIONS: IGF-1 carries potential for predicting type 2 diabetes, rather than long-term cardiovascular outcomes and post-ACS myocardial infarct size and dysfunction, in hyperglycemic ACS patients