Can adenosine triphosphate be a proxy measure in evaluation of hand disinfection effect?

Contaminated hands may contribute to the transmission of pathogens. In the prevention of healthcare-associated infections the effect of disinfection methods should ideally be possible to measure in a simple way. Microbial cultivation is the reference standard, but it is a rather complicated and time-consuming procedure, and the use of swabs for measuring adenosine triphosphate (ATP) has become a much-used proxy measurement (bioluminescence). We evaluated the effect of three hand-disinfection methods on eradication of Escherichia coli from artificially contaminated hands, using cultivation and ATP measurements in parallel. ATP measurement was found to be an unsuitable method as this reflects the total amount of cellular material left on the hands, not only the viable bacteria.

Commentary on: "Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration".

Circadian variations in the corrected QT (QTc) interval have been documented in clinical trials. Animal models show circadian variations in expression of the cardiac ion channels that are necessary to maintain the heart's electrophysiological properties. Can these diurnal rhythms in QTc affect the ability of a drug to delay cardiac repolarization?

Assessing ECG signal quality indices to discriminate ECGs with artefacts from pathologically different arrhythmic ECGs.

False and non-actionable alarms in critical care can be reduced by developing algorithms which assess the trueness of an arrhythmia alarm from a bedside monitor. Computational approaches that automatically identify artefacts in ECG signals are an important branch of physiological signal processing which tries to address this issue. Signal quality indices (SQIs) derived considering differences between artefacts which occur in ECG signals and normal QRS morphology have the potential to discriminate pathologically different arrhythmic ECG segments as artefacts. Using ECG signals from the PhysioNet/Computing in Cardiology Challenge 2015 training set, we studied previously reported ECG SQIs in the scientific literature to differentiate ECG segments with artefacts from arrhythmic ECG segments. We found that the ability of SQIs to discriminate between ECG artefacts and arrhythmic ECG varies based on arrhythmia type since the pathology of each arrhythmic ECG waveform is different. Therefore, to reduce the risk of SQIs classifying arrhythmic events as noise it is important to validate and test SQIs with databases that include arrhythmias. Arrhythmia specific SQIs may also minimize the risk of misclassifying arrhythmic events as noise.

Late sodium current block for drug-induced long QT syndrome: Results from a prospective clinical trial.

Drug-induced long QT syndrome has resulted in many drugs being withdrawn from the market. At the same time, the current regulatory paradigm for screening new drugs causing long QT syndrome is preventing drugs from reaching the market, sometimes inappropriately. In this study, we report the results of a first-of-a-kind clinical trial studying late sodium (mexiletine and lidocaine) and calcium (diltiazem) current blocking drugs to counteract the effects of hERG potassium channel blocking drugs (dofetilide and moxifloxacin). We demonstrate that both mexiletine and lidocaine substantially reduce heart-rate corrected QT (QTc) prolongation from dofetilide by 20 ms. Furthermore, all QTc shortening occurs in the heart-rate corrected J-Tpeak (J-Tpeak c) interval, the biomarker we identified as a sign of late sodium current block. This clinical trial demonstrates that late sodium blocking drugs can substantially reduce QTc prolongation from hERG potassium channel block and assessment of J-Tpeak c may add value beyond only assessing QTc.

Results from the IQ-CSRC prospective study support replacement of the thorough QT study by QT assessment in the early clinical phase.

The QT effects of five "QT-positive" and one negative drug were tested to evaluate whether exposure-response analysis can detect QT effects in a small study with healthy subjects. Each drug was given to nine subjects (six for placebo) in two dose levels; positive drugs were chosen to cause 10 to 12 ms and 15 to 20 ms QTcF prolongation. The slope of the concentration/ΔQTc effect was significantly positive for ondansetron, quinine, dolasetron, moxifloxacin, and dofetilide. For the lower dose, an effect above 10 ms could not be excluded, i.e., the upper bound of the confidence interval for the predicted mean ΔΔQTcF effect was above 10 ms. For the negative drug, levocetirizine, a ΔΔQTcF effect above 10 ms was excluded at 6-fold the therapeutic dose. The study provides evidence that robust QT assessment in early-phase clinical studies can replace the thorough QT study.

Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil.

Block of the hERG potassium channel and prolongation of the QT interval are predictors of drug-induced torsade de pointes. However, drugs that block the hERG potassium channel may also block other channels that mitigate torsade risk. We hypothesized that the electrocardiogram can differentiate the effects of multichannel drug block by separate analysis of early repolarization (global J-Tpeak) and late repolarization (global Tpeak-Tend). In this prospective randomized controlled clinical trial, 22 subjects received a pure hERG potassium channel blocker (dofetilide) and three drugs that block hERG and either calcium or late sodium currents (quinidine, ranolazine, and verapamil). The results show that hERG potassium channel block equally prolongs early and late repolarization, whereas additional inward current block (calcium or late sodium) preferentially shortens early repolarization. Characterization of multichannel drug effects on human cardiac repolarization is possible and may improve the utility of the electrocardiogram in the assessment of drug-related cardiac electrophysiology.

Improving the assessment of heart toxicity for all new drugs through translational regulatory science.

Fourteen drugs have been removed from the market worldwide because they cause torsade de pointes. Most drugs that cause torsade can be identified by assessing whether they block the human ether à gogo related gene (hERG) potassium channel and prolong the QT interval on the electrocardiogram. In response, regulatory agencies require new drugs to undergo "thorough QT" studies. However, some drugs block hERG potassium channels and prolong QT with minimal torsade risk because they also block calcium and/or sodium channels. Through analysis of clinical and preclinical data from 34 studies submitted to the US Food and Drug Administration and by computer simulations, we demonstrate that by dividing the QT interval into its components of depolarization (QRS), early repolarization (J-Tpeak), and late repolarization (Tpeak-Tend), along with atrioventricular conduction delay (PR), it may be possible to determine which hERG potassium channel blockers also have calcium and/or sodium channel blocking activity. This translational regulatory science approach may enable innovative drugs that otherwise would have been labeled unsafe to come to market.

Immediately restored one-piece single-tooth implants with reduced diameter: one-year results of a multi-center study.

OBJECTIVES: The aim of the present multi-center study was to evaluate the treatment outcome of immediately restored one-piece single-tooth implants with a diameter of 3 mm after 1 year. MATERIAL AND METHODS: A total of 57 one-piece implants (NobelDirect 3.0) were inserted in 47 patients (26 females, 21 males) with a mean age of 31 years (range: 17-76 years) at five different centers. The implants replaced maxillary lateral incisors and mandibular incisors. The implants were placed either in conjunction with tooth extraction or in healed sites, and all implants were immediately restored with a provisional resin crown. If needed, the abutment part of the implant was prepared before crown cementation. The permanent crown was placed after 1.9-14.5 months. Radiographs were taken at implant insertion as well as after 6 and 12 months to evaluate the peri-implant marginal bone level and bone loss. Moreover, plaque, bleeding on probing and complications were assessed. RESULTS: A total of 44 patients (23 females, 21 males) with 54 implants were available for the 1-year follow-up. One implant was lost, thus the 1-year implant survival was 98%. A statistically significant mean marginal bone loss was observed between baseline and 6 months (1.1 mm, range: -0.7 to 4.4 mm; n=49) and between baseline and 12 months (1.6 mm, range: -0.8 to 4.6 mm; n=50). A total of 18% of the implants were characterized by a bone loss of more than 3 mm. No bleeding on probing was observed around 83% of the implants. Plaque was registered at 15% of the implants. The most common complications were related to the provisional crown, i.e. fracture (n=3) and loss of retention (n=3). CONCLUSIONS: A high 1-year implant survival was observed in the present study. However, the excessive peri-implant marginal bone loss around several implants indicates that this implant should be used with caution until further studies have been conducted.

Analysis of T-wave Amplitude Adaptation to Heart Rate Using RR-binning of Long-Term ECG Recordings.

The prognosis of patients with coronary artery disease at the early stage of the disease is a challenge of modern cardiology. There is an urgent need to risk stratify these patients. Holter technology is a cheap and cost effective tool to evaluate electrical abnormalities in the heart. We propose to investigate T-amplitude adaptation to heart rate (HR) using RR-binning. We used daytime recordings from healthy subjects and subjects with acute myocardial infarction (AMI) from the Telemetric and Holter ECG Warehouse. The AMI subjects were divided into two groups based on location of their infarction (group A: anterior or anterior lateral, group B: inferior or inferior lateral). Both AMI groups had acute and stable phase recordings. Population-based T-adaptation to HR was observed for healthy subjects (R2 = 0.92) but was less pronounced for AMI subjects: [Formula: see text].

A Comparison of IIR and Wavelet Filtering for Noise Reduction of the ECG.

This study compares the ability to preserve information and reduce noise contaminants on the ECG for five wavelet filters and three IIR filters. Two 3-lead Holter ECGs were used. White Gaussian Noise was added to the first ECG in increments of 10% coverage. The second ECG contained alternating muscle transients and noise-free segments. Computation times and SNR improvements for different noise coverages were calculated and compared. RMS errors were calculated from noise-free segments on the ECG with transient muscle noise. Wavelet filters improved SNR more than IIR filters when the signal coverage was more than 50% noise. In contrast, the computation times were shorter for IIR filters (6 s) than for wavelet filters (88 s). On the ECG with transient muscle noise there was a trade-off in performance between wavelet and IIR filtering. In a clinical setting where the amount of noise is unknown, using IIR filters appears to be preferred for consistent performance.

A Wavelet-Based Algorithm for Delineation and Classification of Wave Patterns in Continuous Holter ECG Recordings.

Quantitative analysis of the electrocardiogram (ECG) requires delineation and classification of the individual ECG wave patterns. We propose a wavelet-based waveform classifier that uses the fiducial points identified by a delineation algorithm. For validation of the algorithm, manually annotated ECG records from the QT database (Physionet) were used. ECG waveform classification accuracies were: 85.6% (P-wave), 89.7% (QRS complex), 92.8% (T-wave) and 76.9% (U-wave). The proposed classification method shows that it is possible to classify waveforms based on the points obtained during delineation. This approach can be used to automatically classify wave patterns in long-term ECG recordings such as 24-hour Holter recordings.

Variable expression of delayed hypersensitivity in different mouse strains using dimethyl dioctadecyl ammonium bromide as an adjuvant.

Delayed-type hypersensitivity measured as footpad swelling was studied in large number of inbred mouse strains. A conjugate of bovine serum albumin (BSA) with the small 2,4-dinitrophenyl (DNP) hapten served to generate strong reactions, specific for the DNP group. Delayed hypersensitivity was produced with the DNP-BSA complex mixed with the cationic, surface active lipid, dimethyl dioctadecyl ammonium bromide (DDA). Great variation was observed in delayed hypersensitivity among different mouse strains. For convenience, the mice were classified into five groups, notably: non-, low, moderate, good and high responders. The highest responding animals were BALB/cJ mice, the lowest were P/JN and outbred nu/nu mice. No correlation was observed between H-2 type and the intensity of the elicited reactions.

Specificity of murine delayed-type hypersensitivity to conjugates of large or small haptens on protein carriers bearing lipid groups.

Delayed-type hypersensitivity (DH) in the mouse was provoked with different hapten-carrier complexes mixed with the cationic, surface-active lipid, dimethyl dioctadecyl ammonium bromide (DDA). DH was measured as footpad swelling. Conjugates of bovine serum albumin (BSA) with the small haptens dinitrophenyl (DNP), 'arsonate' (ARS) and 'sulphonate' (SULPH) served to generate strong DH reactions towards the homologous antigen. Insertion of a tripeptide spacer between the hapten and carrier resulted in lower DH reactivity. Optimal dosages and optimal time intervals between sensitization and DH elicitation were determined for the enlarged hapten-carrier complexes. Cyclophosphamide (CY) treatment, before priming with complexes mixed with DDA, caused a 5-6 day delay in the expression of DH but failed to evoke enhanced DH for any of the antigens tested. A broad array of cross reactions between small and enlarged hapten-carrier complexes showed a relative lack of specificity in these DH responses. The results are compared with others reported in the literature and are explained mainly by the effects of electrostatically bound lipid groups of DDA in the sensitizing conjugates.