Drone exploration of bat echolocation: A UAV-borne multimicrophone array to study bat echolocation.

Multimicrophone array techniques offer crucial insight into bat echolocation, yet they severely undersample the environments bats operate in as they are limited in geographic placement and mobility. UAVs are excellent candidates to greatly increase the environments in which such arrays can be deployed, but the impact of UAV noise on recording quality and the UAV's behavioral impact on the bats may affect usability. We developed a UAV-borne multimicrophone setup capable of recording bat echolocation across diverse environments. We quantify and mitigate the impact of UAV noise on the recording setup and test the recording capability of the array by recording four common Danish bat species: Pipistrellus pygmaeus, Myotis daubentonii, Eptesicus serotinus, and Nyctalus noctula. The UAV produces substantial noise at ultrasonic frequencies relevant to many bat species. However, suspending the array 30 m below the UAV attenuates the noise to levels below the self-noise of our recording system at 20 kHz and above, and we successfully record and acoustically localize all four bat species. The behavioral impact of the UAV is minimal as all four species approached the array to within 1 m and all emitted recordable feeding buzzes. UAV-borne multimicrophone arrays will allow us to quantify bat echolocation in hitherto unexplored habitats and provide crucial insight into how bats operate their sonar across their entire natural habitat.

Agreement between public register and adjudication committee outcome in a cardiovascular randomized clinical trial.

UNLABELLED: The objective of this study is to describe the agreement between randomized trial outcome assessment by committee and outcomes entirely identified through public registers. METHODS: In the CLARICOR trial, 4,372 patients with stable coronary heart disease received a short course of clarithromycin versus placebo and were followed up for 2.6 years. The pertinent hospital records and death certificates had originally been evaluated by the adjudication committee using common definitions of outcomes mapped into a 6-category list. We now mechanically converted the International Classification of Diseases-coded diagnoses of the public registries into the same categories. After cross-tabulation of the committee diagnoses with National Patient Register diagnoses and Register of Causes of Death, we calculate agreement and compare the estimated intervention effects of the 2 data sets. RESULTS: With public register data, the protocol-specified categories were slightly more frequent. Overall agreement was 74% for hospital discharges and 60% for cause of death, but the intervention effect, expressed as a hazard ratio, stayed within 4% of the value originally obtained with the adjudication committee (P ≥ .35). CONCLUSIONS: Our results show a modest agreement between formal adjudication and outcomes deducible from public registers. However, the estimated intervention effect did not differ noticeably between the 2 data sources. If studies on a wide range of public registers confirm these findings, register outcomes may be considered as a replacement for adjudication committees.

Safe application of a restrictive transfusion protocol in moderate-risk patients undergoing cardiac operations.

BACKGROUND: Perioperative red blood cell transfusion is associated with adverse outcomes after cardiac operations. Although restrictive transfusion protocols have been developed, their safety and efficacy are not well demonstrated, and considerable variation in transfusion practice persists. We report our experience with a restrictive transfusion protocol. METHODS: We analyzed the outcomes in 409 patients undergoing cardiac operations enrolled in a trial conducted at 30 centers worldwide. Blood products were administered on the basis of a transfusion algorithm applied across all centers, with a restrictive transfusion trigger of hemoglobin less than or equal to 6 g/dL. Transfusion was acceptable but not mandatory for hemoglobin 6 to 8 g/dL. For hemoglobin 8 to 10 g/dL, transfusion was acceptable only with evidence for end-organ ischemia. RESULTS: The patient population was moderately complex, with 20.5% having combined procedures and 29.6% having nonelective operations. The mean EuroSCORE for the population was 4.3, which predicted a substantial incidence of morbidity and mortality. Actual outcomes were excellent, with observed mortality of 0.49% and rates of cerebrovascular accident, myocardial infarction, and acute renal failure 1.2%, 6.1%, and 0.98%, respectively. The frequency of red blood cell transfusion was 33.7%, which varied significantly by center. Most transfusions (71.9%) were administered for hemoglobin 6 to 8 g/dL; 21.4% were administered for hemoglobin 8 to 10 g/dL with evidence for end-organ ischemia; 65.0% of patients avoided allogeneic transfusion altogether. CONCLUSIONS: A restrictive transfusion protocol can be safely applied in the care of moderate-risk patients undergoing cardiac operations. This strategy has significant potential to reduce transfusion and resource utilization in these patients, standardize transfusion practices across institutions, and increase the safety of cardiac operations.

Efficacy and safety of recombinant factor XIII on reducing blood transfusions in cardiac surgery: a randomized, placebo-controlled, multicenter clinical trial.

OBJECTIVES: Cardiac surgery with cardiopulmonary bypass frequently leads to excessive bleeding, obligating blood product transfusions. Because low factor XIII (FXIII) levels have been associated with bleeding after cardiac surgery, we investigated whether administering recombinant FXIII after cardiopulmonary bypass would reduce transfusions. METHODS: In this double-blinded, placebo-controlled, multicenter trial, 409 cardiac surgical patients at moderate risk for transfusion were randomized to receive an intravenous dose of recombinant FXIII, 17.5 IU/kg (n = 143), 35 IU/kg (n = 138), or placebo (n = 128) after cardiopulmonary bypass. Transfusion guidelines were standardized. The primary efficacy outcome was avoidance of allogeneic blood products for 7 days postsurgery. Secondary outcomes included amount of blood products transfused and reoperation rate. Serious adverse events were measured for 7 weeks. RESULTS: Study groups had comparable baseline characteristics and an approximately 40% decrease in FXIII levels after cardiopulmonary bypass. Thirty minutes postdose, FXIII levels were restored to higher than the lower 2.5th percentile of preoperative activity in 49% of the placebo group, and 85% and 95% of the 17.5- and 35-IU/kg recombinant FXIII groups, respectively (P < .05 for both treatments vs placebo). Transfusion avoidance rates were 64.8%, 64.3%, and 65.9% with placebo, 17.5 IU/kg, and 35 IU/kg recombinant FXIII (respective odds ratios against placebo, 1.05 [95% confidence interval, 0.61-1.80] and 0.99 [95% confidence interval, 0.57-1.72]). Groups had comparable adverse event rates. CONCLUSIONS: Replenishment of FXIII levels after cardiopulmonary bypass had no effect on transfusion avoidance, transfusion requirements, or reoperation in moderate-risk cardiac surgery patients (ClinicalTrials.gov identifier: NCT00914589).

Good interobserver agreement was attainable on outcome adjudication in patients with stable coronary heart disease.

OBJECTIVE: In clinical trials, agreement on outcomes is of utmost importance for valid estimation of intervention effects. As there is limited knowledge about adjudicator agreement in cardiology, we examined the level of agreement among three cardiology specialists adjudicating all possible events in a randomized controlled clinical trial of patients with stable coronary heart disease. STUDY DESIGN AND SETTING: All information (hospital records, death certificates, etc.) was forwarded to two randomly selected blinded adjudicators. If they disagreed, the third arbiter had to choose the more likely of the two alternatives. Files of 5,475 nonfatal and 362 fatal events were evaluated. RESULTS: For nonfatal outcomes, pairwise kappa values ranged from 0.75 to 0.80. The three adjudicators had 4.3%, 9.5%, and 6.1% of their nonfatal outcome classifications overruled by their arbiter. If stable angina pectoris, unstable angina pectoris, and acute myocardial infarction were treated as one, agreement increased minimally. For fatal outcomes, the pairwise kappa values ranged from 0.65 to 0.90. The three adjudicators had 12%, 9%, and 10% of their death classifications overruled. CONCLUSION: Specialists in cardiology can attain a reasonably high agreement on outcomes in patients with stable coronary heart disease.

Excess sudden cardiac deaths after short-term clarithromycin administration in the CLARICOR trial: why is this so, and why are statins protective?

OBJECTIVES: To elucidate potential mechanisms for the clarithromycin-induced excess mortality observed in the CLARICOR trial during 2.6 year follow-up of patients with stable coronary artery disease. METHODS: Cox analyses using out-of-hospital death as a proxy for sudden death compared to in-hospital (nonsudden) death. RESULT: In 100 of 189 (53%) cardiovascular (CV) deaths in which it was possible to examine the question, there was a strong association between place of death and the classification of CV death as sudden or not-sudden. The excess mortality in the clarithromycin group was confined to sudden CV death in patients not on statins at trial entry (HR: 2.61, 95% CI: 1.69-4.05, p < 0.0005). Other categories of deaths showed no marked drug-placebo difference. CONCLUSIONS: Short-term clarithromycin administration was significantly associated with increased risk of sudden CV death in stable coronary heart disease patients not using statins.

High-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide in patients with stable coronary artery disease: a prognostic study within the CLARICOR trial.

BACKGROUND: Patients with stable coronary artery disease (CAD) have a poor prognosis. The aim of the study was to evaluate the extent to which serum high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement alone or together could be prognostic biomarkers in patients with stable CAD. MATERIALS AND METHODS: During the 2.6-year follow-up period 270 patients among the 4264 patients with stable CAD in the CLARICOR trial suffered myocardial infarction (MI) and 377 died (187 cardiovascular deaths (CVD)). RESULTS: Serum NT-proBNP was significantly associated with MI (hazard ratio (HR), 1. 65 (refers to a 2.72 fold increase in serum level, p = 0.0005), CVD (HR, 2.42, p < 0.0005) and non-CVD (HR, 1.79, p < 0.0005). When correcting for hs-CRP, NT-proBNP was still significantly associated with MI (HR, 1.63, p = 0.0005), CVD (HR, 2.36, p < 0.0005) and non-CVD (HR, 1.66, p < 0.0005). Serum hs-CRP was compared to NT-proBNP less associated with MI (HR, 1.20, p = 0.001), CVD (HR, 1.39, p < 0.0005) and non-CVD (HR, 1.67, p < 0.0005). When corrected for NT-proBNP, hs-CRP was only associated with non-CVD (HR, 1.51, p < 0.0005). When adjusting for cardiovascular risk factors hs-CRP predicted non-CVD (HR, 1.46) and all-cause death (HR, 1.24) and NT-proBNP predicted MI (HR, 1.50), CVD (HR, 1.98), non-CVD (HR, 1.39), and all-cause death (HR, 1.62)(p < 0.0005 for all). CONCLUSION: Increased serum NT-proBNP was a stronger predictor of MI, cardiovascular death and non-cardiovascular death than hs-CRP in patients with stable CAD. Once NT-proBNP was taken into account, hs-CRP did not improve predictions.

Chlamydia pneumoniae IgG and IgA antibody titers and prognosis in patients with coronary heart disease: results from the CLARICOR trial.

The association observed between coronary heart disease (CHD) and Chlamydia (Chlamydophila) pneumoniae antibodies prompted, during the 1990s, several primary and secondary prevention trials with various antibiotics. In our CLARICOR trial, a randomized placebo-controlled trial in 4372 patients with stable CHD, a brief clarithromycin regimen was followed, unexpectedly, by increased long-term mortality. We now compare C. pneumoniae antibody levels at entry with population levels, with the patients' individual histories, and with their subsequent outcomes. IgG antibody levels were somewhat raised, but elevated IgA and IgG titers were unrelated to entry data (including prior acute myocardial infarction), except for an association with smoking and with not using statins. Hazards of mortality and of other outcomes tended to slightly increase with IgA and decrease with IgG titers, but the unfavorable clarithromycin effect was unrelated to antibody levels and remains unexplained. Smoking-related lung disease probably underlies the link between heart disease and increased IgG titers.

Statin treatment prevents increased cardiovascular and all-cause mortality associated with clarithromycin in patients with stable coronary heart disease.

In the CLARICOR trial, significantly increased cardiovascular (CV) and all-cause mortality in stable patients with coronary heart disease were observed after a short course of clarithromycin. We report on the impact of statin treatment at entry on the CV and all-cause mortality. The multicenter CLARICOR trial randomized patients to oral clarithromycin (500 mg daily; n = 2172) versus matching placebo (daily; n = 2201) for 2 weeks. Patients were followed through public databases. In the 41% patients on statin treatment at entry, no significant effect of clarithromycin was observed on CV (hazard ratio [HR], 0.68, 95% confidence interval [CI], 0.38-1.22; P = 0.20) or all-cause mortality (HR, 1.08; 95% CI, 0.71-1.65; P = 0.72) at 2.6-year follow up. In the patients not on statin treatment at entry, clarithromycin was associated with a significant increase in CV (HR, 1.90; 95% CI, 1.34-2.67; P = 0.0003; statin-clarithromycin interaction P = 0.0029) and all-cause mortality (HR, 1.33; 95% CI, 1.05-1.67; P = 0.016; statin-clarithromycin interaction P = 0.41). Multivariate analysis and 6-year follow up confirmed these results. Concomitant statin treatment in stable patients with coronary heart disease abrogated the observed increased CV mortality associated with 2 weeks of clarithromycin.

Repletion of factor XIII following cardiopulmonary bypass using a recombinant A-subunit homodimer. A preliminary report.

Bleeding following cardiac surgery involving cardiopulmonary bypass (CPB) remains a major concern. Coagulation factor XIII (FXIII) functions as a clot-stabilising factor by cross-linking fibrin. Low post-operative levels of FXIII correlate with increased post-operative blood loss. To evaluate preliminary safety and pharmacokinetics of recombinant FXIII (rFXIII-A(2)) in cardiac surgery, patients scheduled for coronary artery bypass grafting were randomised to receive a single dose of either rFXIII-A(2) (11.9, 25, 35 or 50 IU/kg) or placebo in a 4:1 ratio. Study drug was given post-CPB within 10 to 20 minutes after first protamine dose. Patients were evaluated until day 7 or discharge, with a follow-up visit at weeks 5-7. The primary end-point was incidence and severity of adverse events. Thirty-five patients were randomised to rFXIII-A(2) and eight to placebo. Eighteen serious adverse events were reported. These were all complications well recognised during cardiac surgery. Although one patient required an implantable defibrillator, all recovered without sequelae. One myocardial infarction in a patient receiving 35 IU/kg rFXIII-A(2) was identified by the Data Monitoring Committee after reviewing ECGs and cardiac enzymes. No other thromboembolic events were seen. Dosing with 25-50 IU/kg rFXIII-A(2) restored levels of FXIII to pre-operative levels, with a tendency towards an overshoot in receiving 50 IU/kg. rFXIII-A(2), in doses from 11.9 IU/kg up to 50 IU/kg, was well tolerated. For post-operative FXIII replenishment, 35 IU/kg of rFXIII-A(2) may be the most appropriate dose.

High serum YKL-40 concentration is associated with cardiovascular and all-cause mortality in patients with stable coronary artery disease.

AIMS: Macrophages in atherosclerotic plaques secrete YKL-40. We tested the hypothesis if high serum YKL-40 concentration predicts coronary events and death of patients with stable coronary artery disease (CAD). METHODS AND RESULTS: During the 2.6 years follow-up period (median 2.77 year, interquartile range 0.23 year), 270 patients among the 4298 patients with stable CAD in the CLARICOR trial suffered myocardial infarction (MI) and 377 died (187 classified as cardiovascular death). Serum YKL-40 transformed as Y=log[max(82, serum YKL-40/microg/L)] was significantly associated with cardiovascular death [hazard ratio (HR) = 1.88, 95% confidence interval (CI) = 1.54-2.31, P < 0.001], all-cause mortality (HR = 2.01, 95% CI = 1.75-2.31, P < 0.001), and MI (HR = 1.38, 95% CI = 1.13-1.68, P = 0.002). Following multivariable adjustment for cardiovascular risk factors (age, sex, previous MI, smoking status, hypertension, diabetes mellitus) and selected medical treatments Y contributed significantly to prediction of all-cause mortality (P < 0.001) and cardiovascular mortality (P = 0.001), but not MI (P = 0.25). CONCLUSION: High serum YKL-40 is associated with MI, cardiovascular and all-cause mortality in patients with stable CAD.

Clarithromycin for 2 weeks for stable coronary heart disease: 6-year follow-up of the CLARICOR randomized trial and updated meta-analysis of antibiotics for coronary heart disease.

OBJECTIVES: We have reported increased 2.6-year mortality in clarithromycin- versus placebo-exposed stable coronary heart disease patients, but meta-analysis of randomized trials in coronary heart disease patients showed no significant effect of antibiotics on mortality. Here we report the 6-year mortality of clarithromycin- versus placebo-exposed patients and updated meta-analyses. METHODS: Centrally randomized, placebo controlled multicenter trial. All parties were blinded. Analyses were by intention to treat. Meta-analyses followed the Cochrane Collaboration methodology. RESULTS: We randomized 4,372 patients with stable coronary heart disease to clarithromycin 500 mg (n = 2,172) or placebo (n = 2,200) once daily for 2 weeks. Mortality was followed through public register. Nine hundred and twenty-three patients (21.1%) died. Six-year mortality was significantly higher in the clarithromycin group (hazard ratio 1.21, 95% confidence interval 1.06-1.38). Adjustment for entry characteristics (sex, age, prior myocardial infarction, center, and smoking) did not change the results (1.18, 1.04-1.35). Addition of our data to that of other randomized trials on antibiotics for patients with coronary heart disease versus placebo/no intervention (17 trials, 25,271 patients, 1,877 deaths) showed a significantly increased relative risk of death from antibiotics of 1.10 (1.01-1.20) without heterogeneity. CONCLUSIONS: Our results stress the necessity to consider carefully the strength of the indication before administering antibiotics to patients with coronary heart disease.

Myocardial stress in patients with acute cerebrovascular events.

Signs of myocardial involvement are common in patients with acute cerebrovascular events. ST segment deviations, abnormal left ventricular function, increased N-terminal pro-brain natriuretic peptide (NT-proBNP), prolonged QT interval, and/or raised troponins are observed in up to one third of the patients. The huge majority of these findings are fully reversible. The changes may mimic myocardial infarction, but are not necessarily identical to coronary thrombosis. Based on the literature these signs may represent an acute catecholamine release provoked by the cerebrovascular catastrophe itself and not coronary thrombosis. However, all patients with signs of cardiac involvement during acute cerebrovascular events should receive a cardiological follow-up in order to exclude concomitant ischemic heart disease.

Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial.

OBJECTIVE: To determine if the macrolide clarithromycin affects mortality and cardiovascular morbidity in patients with stable coronary heart disease. DESIGN: Centrally randomised multicentre trial. All parties at all stages were blinded. Analyses were by intention to treat. SETTING: Five Copenhagen University cardiology departments and a coordinating centre. PARTICIPANTS: 13,702 patients aged 18 to 85 years who had a discharge diagnosis of myocardial infarction or angina pectoris in 1993-9 and alive in August 1999 were invited by letter; 4373 were randomised. INTERVENTIONS: Two weeks' treatment with clarithromycin 500 mg/day or matching placebo. PRIMARY OUTCOME: composite of all cause mortality, myocardial infarction, or unstable angina pectoris during three years' follow-up. Secondary outcome: composite of cardiovascular mortality, myocardial infarction, or unstable angina pectoris. The outcomes were obtained from Danish registers and were blindly assessed by the event committee. RESULTS: 2172 participants were randomised to clarithromycin and 2201 to placebo. We found no significant effects of clarithromycin on the primary outcome (hazard ratio 1.15, 95% confidence interval 0.99 to 1.34) or secondary outcome (1.17, 0.98 to 1.40). Mortality was significantly higher in the clarithromycin arm (1.27, 1.03 to 1.54; P = 0.03) as a result of significantly higher cardiovascular mortality (1.45, 1.09 to 1.92; P = 0.01). CONCLUSIONS: Short term clarithromycin in patients with stable coronary heart disease may cause significantly higher cardiovascular mortality. The long term safety of clarithromycin in patients with stable ischaemic heart disease should be examined. Trial registration ClinicalTrials.gov NCT00121550.

[Compartment syndrome following a hematoma in leg muscles, initially interpreted as deep venous thrombosis]. / Kompartmentsyndrom som følge af haematom i laegmuskulaturen mistaenkt som dyb venetrombose.

An otherwise healthy 48-year-old Caucasian male was admitted to hospital due to suspicion of right calf thrombosis. The symptoms were intermittent thickening and tension of the right calf for four days. There was no history of trauma. Clinical signs and symptoms and a d-dimer of 1.4 (< 0.5 mg/l) indicated deep venous thrombosis, and anticoagulation treatment was started with confirmatory ultrasound planned for the following morning. Overnight, the pains and swelling increased significantly and decreased sensitivity on the medial side of the foot was found, suggesting compartment syndrome. Ultrasound showed no sign of DVT, but a large haematoma was seen in the deep posterior compartment of the calf, and an acute fasciotomy was done. This case report emphasizes the importance of utilising ultrasound before starting anticoagulation therapy in patients suspected of having DVT.