Characterization and financial impact of implantable cardioverter-defibrillator patients without interventions 5 years after implantation

Background: Implantable cardioverter defibrillators (ICD's) are increasingly used for primary and secondary prevention of sudden cardiac death. However, data on how many ICD patients indeed receive appropriate ICD therapy during long-term follow-up is scarce. Aim: The aim of our study was to determine the number of patients without appropriate ICD therapy 5 years after ICD implantation, to identify predicting factors, to assess the occurrence of late first ICD therapy and to quantify the financial impact of ICD therapy in a real-world setting. Design: Prospective observational study. Methods: We prospectively enrolled 322 consecutive ICD patients. Baseline data were collected at implantation and patients were followed for a median of 7.3 years (IQR 5.8-9.2 years). Time to first appropriate ICD therapy (either antitachycardia pacing or cardioversion) was documented. Results: Five years after implantation, 139 patients (43%) had not received appropriate ICD therapy. In multivariable analysis, a primary prevention indication and negative electrophysiological studies prior to ICD implantation were independent predictors of freedom from ICD therapy. Of the patients without ICD therapy, 5 years after implantation, 25% had experienced inappropriate ICD shocks. Two hundred and seven devices (1.5 devices per patient) were needed for the 139 patients without ICD intervention within 5 years, accounting for €31 784 per patient. During an additional follow-up of 3 years, 12% of the patients with unused ICD received a late first appropriate ICD therapy. Conclusions: About half of the ICD patients receive appropriate ICD therapy within 5 years after implantation. Furthermore, there is a significant proportion of patients receiving late first shocks after five initially uneventful year

Optimal cutoff-value of Siemens cardiac troponin I assay in patients with kidney disease for the early diagnosis of acute myocardial infarction

Purpose: The recent introduction of more sensitive cardiac troponin (cTn) assays improved the early diagnosis of acute myocardial infarction (AMI). However, its diagnostic utility has never been tested in patients with kidney disease (KD), who are known to have elevated levels of cTn already in the absence of AMI, which may lead to a lower diagnostic value of more sensitive cTn in this high-risk subgroup. Methods: We conducted an international multicenter study to examine the diagnostic accuracy of the Siemens cTnI Ultra assay in 1997 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, of whom 343 (17%) were determined to have KD (MDRD GFR <60ml/min/1.73m2) and to derive the optimal cutoff-value for the diagnosis of AMI in patients with KD. The diagnostic accuracy was further compared to a conventional cTn assay (Roche Troponin T fourth generation). The final diagnosis was adjudicated by two independent cardiologists based on hs-cTnT. Results: AMI was the final diagnosis in 35% (n=120) of all KD-patients as compared to 18% in patients with normal kidney function (p<0.001). Among KD-patients with other diagnoses than AMI, baseline hs-cTnI-levels were elevated above the 99thpercentile in 20%, In patients with KD the diagnostic accuracy at presentation, quantified by the area under the receiver-operator-characteristic curve (AUC), was significantly greater for Siemens cTnI as compared to the standard cTnT assay (AUC for cTnI, 0.88 vs. AUC for the standard assay, 0.82, p=0.013). In patients presenting within three hours after the onset of chest pain, the superiority of Siemens cTnI over conventional cTnT was even more pronounced (AUC 0.86 vs. 0.72, p=0.005). In KD, the optimal hs-cTnI cutoff derived from the ROC curve was 46 ng/l compared to 19 ng/l in patients with normal kidney function (standard 99th percentile 40 ng/l, provided by the manufacturer). Conclusions: The Siemens cTnI Ultra assay has a very high diagnostic accuracy also in KD-patients and is superior to a conventional cTnT-assay. Mild cTnI elevations are common in non-AMI patients. The optimal cutoff-level in KD-patients seems to be around the 99th percentile of a standard population, whereas the optimal cutoff-level in patients with normal kidney function tends to be only half of the suggested cutoff-value. ClinicalTrials.gov number, NCT0047058

Contact force sensing in ablation of ventricular arrhythmias using a 56-hole open-irrigation catheter: a propensity-matched analysis.

PURPOSE: The effect of adding contact force (CF) sensing to 56-hole tip irrigation in ventricular arrhythmia (VA) ablation has not been previously studied. We aimed to compare outcomes with and without CF sensing in VA ablation using a 56-hole radiofrequency (RF) catheter. METHODS: A total of 164 patients who underwent first-time VA ablation using Thermocool SmartTouch Surround Flow (TC-STSF) catheter (Biosense-Webster, Diamond Bar, CA, USA) were propensity-matched in a 1:1 fashion to 164 patients who had first-time ablation using Thermocool Surround Flow (TC-SF) catheter. Patients were matched for age, gender, cardiac aetiology, ejection fraction and approach. Acute success, complications and long-term follow-up were compared. RESULTS: There was no difference between procedures utilising either TC-SF or TC-STSF in acute success (TC-SF: 134/164 (82%), TC-STSF: 141/164 (86%), p = 0.3), complications (TC-SF: 11/164 (6.7%), TC-STSF: 11/164 (6.7%), p = 1.0) or VA-free survival (TC-SF: mean arrhythmia-free survival time = 5.9 years, 95% CI = 5.4-6.4, TC-STSF: mean = 3.2 years, 95% CI = 3-3.5, log-rank p = 0.74). Fluoroscopy time was longer in normal hearts with TC-SF (19 min, IQR: 14-30) than TC-STSF (14 min, IQR: 8-25; p = 0.04). CONCLUSION: Both TC-SF and TC-STSF catheters are safe and effective in treating VAs. The use of CF sensing catheters did not improve safety or acute and long-term outcomes, but reduced fluoroscopy time in normal heart VA

High-Pressure Amorphous Nitrogen

The phase diagram and stability limits of diatomic solid nitrogen have been explored in a wide pressure--temperature range by several optical spectroscopic techniques. A newly characterized narrow-gap semiconducting phase $\eta$ has been found to exist in a range of 80--270 GPa and 10--510 K. The vibrational and optical properties of the $\eta$ phase produced under these conditions indicate that it is largely amorphous and back transforms to a new molecular phase. The band gap of the $\eta$ phase is found to decrease with pressure indicating possible metallization by band overlap above 280 GPa.Comment: 5 pages, 4 figure

Stable isotope analysis provides new information on winter habitat use of declining avian migrants that is relevant to their conservation

Winter habitat use and the magnitude of migratory connectivity are important parameters when assessing drivers of the marked declines in avian migrants. Such information is unavailable for most species. We use a stable isotope approach to assess these factors for three declining African-Eurasian migrants whose winter ecology is poorly known: wood warbler Phylloscopus sibilatrix, house martin Delichon urbicum and common swift Apus apus. Spatially segregated breeding wood warbler populations (sampled across a 800 km transect), house martins and common swifts (sampled across a 3,500 km transect) exhibited statistically identical intra-specific carbon and nitrogen isotope ratios in winter grown feathers. Such patterns are compatible with a high degree of migratory connectivity, but could arise if species use isotopically similar resources at different locations. Wood warbler carbon isotope ratios are more depleted than typical for African-Eurasian migrants and are compatible with use of moist lowland forest. The very limited variance in these ratios indicates specialisation on isotopically restricted resources, which may drive the similarity in wood warbler populations' stable isotope ratios and increase susceptibility to environmental change within its wintering grounds. House martins were previously considered to primarily use moist montane forest during the winter, but this seems unlikely given the enriched nature of their carbon isotope ratios. House martins use a narrower isotopic range of resources than the common swift, indicative of increased specialisation or a relatively limited wintering range; both factors could increase house martins' vulnerability to environmental change. The marked variance in isotope ratios within each common swift population contributes to the lack of population specific signatures and indicates that the species is less vulnerable to environmental change in sub-Saharan Africa than our other focal species. Our findings demonstrate how stable isotope research can contribute to understanding avian migrants' winter ecology and conservation status

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

Cardiac biomarkers of acute coronary syndrome: from history to high-sensitivity cardiac troponin

The role of cardiac troponins as diagnostic biomarkers of myocardial injury in the context of acute coronary syndrome (ACS) is well established. Since the initial 1st-generation assays, 5th-generation high-sensitivity cardiac troponin (hs-cTn) assays have been developed, and are now widely used. However, its clinical adoption preceded guidelines and even best practice evidence. This review summarizes the history of cardiac biomarkers with particular emphasis on hs-cTn. We aim to provide insights into using hs-cTn as a quantitative marker of cardiomyocyte injury to help in the differential diagnosis of coronary versus non-coronary cardiac diseases. We also review the recent evidence and guidelines of using hs-cTn in suspected ACS

Insights into the migration of the European Roller from ring recoveries

AbstractDespite recent advances in avian tracking technology, archival devices still present several limitations. Traditional ring recoveries provide a complementary method for studying migratory movements, particularly for cohorts of birds with a low return rate to the breeding site. Here we provide the first international analysis of ring recovery data in the European Roller Coracias garrulus, a long-distance migrant of conservation concern. Our data comprise 58 records of Rollers ringed during the breeding season and recovered during the non-breeding season. Most records come from Eastern Europe, half are of juveniles and over three quarters are of dead birds. Thus, ring recoveries provide migration data for cohorts of Rollers—juveniles and unsuccessful migrants—for which no information currently exists, complementing recent tracking studies. Qualitatively, our results are consistent with direct tracking studies, illustrating a broad-front migration across the Mediterranean Basin in autumn and the use of the Arabian Peninsula by Rollers from eastern populations in spring. Autumn movements were, on average, in a more southerly direction for juveniles than adults, which were more easterly. Juvenile autumn recovery direction also appeared to be more variable than in adults, though this difference was not statistically significant. This is consistent with juveniles following a naïve vector-based orientation program, and perhaps explains the ‘moderate’ migratory connectivity previously described for the Roller. In the first (qualitative) analysis of Roller non-breeding season mortality, we highlight the high prevalence of shooting. The recovery age ratio was juvenile-biased in autumn but adult-biased in spring. Although not statistically significant, this difference points towards a higher non-breeding season mortality of juveniles than adults. Our study demonstrates the complementarity of ring recoveries to direct tracking, providing an insight into the migration of juvenile Rollers and non-breeding season mortality

Challenging the Moral Status of Blood Donation

The World Health Organisation encourages that blood donation becomes voluntary and unremunerated, a system already operated in the UK. Drawing on public documents and videos, this paper argues that blood donation is regarded and presented as altruistic and supererogatory. In advertisements, donation is presented as something undertaken for the benefit of others, a matter attracting considerable gratitude from recipients and the collecting organisation. It is argued that regarding blood donation as an act of supererogation is wrongheaded, and an alternative account of blood donation as moral obligation is presented. Two arguments are offered in support of this position. First, the principle of beneficence, understood in a broad consequentialist framework obliges donation where the benefit to the recipient is large and the cost to the donor relatively small. This argument can be applied, with differing levels of normativity, to various acts of donation. Second, the wrongness of free riding requires individuals to contribute to collective systems from which they benefit. Alone and in combination these arguments present moral reasons for donation, recognised in communication strategies elsewhere. Research is required to evaluate the potential effects on donation of a campaign which presents blood donation as moral obligation, but of wider importance is the recognition that other-regarding considerations in relation to our own as well as others’ health result in a range not only of choices but also of obligations

Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study

In the emergency setting, non-traumatic headache is a benign symptom in 80% of cases, but serious underlying conditions need to be ruled out. Copeptin improves risk stratification in several acute diseases. Herein, we investigated the value of copeptin to discriminate between serious secondary headache and benign headache forms in the emergency setting.; Patients presenting with acute non-traumatic headache were prospectively enrolled into an observational cohort study. Copeptin was measured upon presentation to the emergency department. Primary endpoint was serious secondary headache defined by a neurologic cause requiring immediate treatment of the underlying disease. Secondary endpoint was the combination of mortality and hospitalization within 3 months. Two board-certified neurologist blinded to copeptin levels verified the endpoints after a structured 3-month-telephone interview.; Of the 391 patients included, 75 (19%) had a serious secondary headache. Copeptin was associated with serious secondary headache (OR 2.03, 95%CI 1.52-2.70, p &lt; 0.0001). Area under the curve (AUC) for copeptin to identify the primary endpoint was 0.70 (0.63-0.76). After adjusting for age &gt; 50, focal-neurological abnormalities, and thunderclap onset of symptoms, copeptin remained an independent predictive factor for serious secondary headache (OR 1.74, 95%CI 1.26-2.39, p = 0.001). Moreover, copeptin improved the AUC of the multivariate logistic clinical model (p-LR-test &lt; 0.001). Even though copeptin values were higher in patients reaching the secondary endpoint, this association was not significant in multivariate logistic regression.; Copeptin was independently associated with serious secondary headache as compared to benign headaches forms. Copeptin may be a promising novel blood biomarker that should be further validated to rule out serious secondary headache in the emergency department.; Study Registration on 08/02/2010 as NCT01174901 at clinicaltrials.gov