[Otorhinolaryngological diseases in pregnancy-which drugs are approved?] / HNO-ärztliche Krankheitsbilder in der Schwangerschaft ­ welche Medikamente sind zulässig?

Between 1958 and 1961 approximately 10,000 children with severe deformities of extremities were born, whose mothers had taken the sedative thalidomide. Since then, drugs in pregnancy are applied with legitimate caution by the pharmaceutical industry, physicians and patients, although often accompanied by irrational panic. The pharmaceutical industry takes a legally safe position noting "contraindication" or at least "strict indication" in the consumer information. This transfers responsibility to the prescribing doctor. Even without drug therapy, the spontaneous malformation rate is approx. 3 to 4%. Concerning expectant mothers, a therapeutic nihilism may lead to a dramatic deterioration of the maternal disease, thereby causing high risks in fetal development. The aim of the present work is to present a structured "Guideline for Practice" of medication that can be used during pregnancy for treating medical conditions of the ear, nose and throat.

Estimating the real-world performance of the PROMISE minimal-risk tool.

BACKGROUND: Stable chest pain is a common indication for cardiac catheterization. We assessed the prognostic value of the Prospective Multicenter Imaging Study for Evaluation (PROMISE) Minimal-Risk Tool in identifying patients who are at very low risk of obstructive coronary artery disease (CAD) or downstream cardiovascular adverse outcomes. METHODS: We applied the PROMISE Minimal-Risk Tool to consecutive patients without known CAD who underwent elective cardiac catheterization for stable angina from January 1, 2000 to December 31, 2014 in the Duke Databank for Cardiovascular Disease (DDCD). Patients with scores >0.46 (top decile of lowest-risk from the PROMISE cohort) were classified as low-risk. Logistic regression modeling compared likelihood of freedom from obstructive coronary artery disease on index angiography, 2-year survival, and 2-year survival free of myocardial infarction (MI) and MI/revascularization between low- and non low-risk patients. Alternative cut points to define low- risk patients were also explored. RESULTS: Among 6251 patients undergoing cardiac catheterization for stable chest pain, 1082 (17.3%) were low-risk per the PROMISE minimal-risk tool. Among low risk patients, obstructive coronary artery disease was observed in 14.9% and left main disease (≥ 50% Stenosis) was rare (0.9%). Compared with other patients, low risk patients had a higher likelihood of freedom from obstructive coronary disease on index catheterization (85.1% vs. 44.2%, OR 4.84, 95% CI 4.06-5.77). Low risk patients had significantly higher survival (98.2% vs. 94.4%, OR 3.18, 95% CI 1.99-5.08), MI-free survival (97.2% vs. 91.9%, OR 3.03, 95% CI 2.07-4.45), and MI/revascularization-free survival (86.2 vs. 59.9%, OR 4.19, 95% CI 3.48-5.05) at 2 years than non-low risk patients. Operating characteristics for predicting the outcomes of interest varied modestly depending on the low-risk cut-point used but the positive predictive value for 2 year freedom from death was >98% regardless. CONCLUSION: The PROMISE minimal-risk tool identifies 17% of stable chest pain patients referred to cardiac catheterization as low risk. These patients have a low prevalence of obstructive CAD and better survival than non-low risk patients. While this suggests that these patients are unlikely to benefit from catheterization, further research is needed to confirm a favorable downstream prognosis with medical management alone.

Time-series analysis of heart rate and blood pressure in response to changes in work rate before and after 60 days of 6° head down tilt bed rest.

PURPOSE: Cardiovascular regulation during exercise, described using time series analysis, is expected to be attenuated after bed rest (BR) and this effect will be dampened by a reactive jumps countermeasure. METHODS: Twenty subjects (29 ± 6 years, 23.6 ± 1.7 kg m-2) were tested on a cycle ergometer 9 days (BDC-9) before the beginning of BR as well as 2 (R + 2) and 13 days (R + 13) after the end of BR, applying moderate pseudo-random binary (PRBS) work rate changes. Heart rate (HR) and mean arterial blood pressure (mBP) were measured beat-to-beat and interpolated to 1 s intervals. HR and mBP were cross-correlated [CCF(HR-mBP)] during the PRBS. Eleven subjects participated in a reactive jump countermeasure (JUMP) during the BR period, the other part of the group served as control group (CTRL). RESULTS: In the CTRL group, significantly lower CCF(HR-mBP) values during BDC-9 were observed compared to R + 2 during the lags 20-25 s and significantly higher values during the lags - 39 s to - 35 s. In the JUMP group, significantly lower CCFs were only observed at R + 2 compared with BDC-9 during the lags 23 s and 24 s, whereas the CCFs for BDC-9 were significantly higher at several lags compared with R + 13. CONCLUSION: Attenuations in the regulation of the cardiovascular system during cycling exercise after BR were found in the CTRL group of the RSL study. Cardiovascular regulation in the JUMP group was improved compared to values before the beginning of BR, suggesting the effectiveness of the reactive jumps countermeasure to mitigate the deleterious effects of prolonged BR.

[Confusion, tachypnea, and tachycardia in a 71-year-old man with type 2 diabetes mellitus]. / Bewusstseinsstörung, Tachypnoe und Tachykardie bei einem 71-jährigen Patienten mit Diabetes mellitus Typ 2.

Patients with type 2 diabetes who present with confusion and/or abdominal pains should be screened for sodium-glucose cotransporter 2 (SGLT-2)-induced diabetic ketoacidosis. Severe acidosis was diagnosed despite only moderately increased blood sugar levels. If so, immediate ICU treatment is essential.

[Model project on interdisciplinary university teaching-medical and psychology students learn together for the first time]. / Modellprojekt zur interdisziplinären universitären Lehre ­ Studierende der Medizin und der Psychologie lernen erstmals gemeinsam.

An interdisciplinary collaboration is required in the medical care of chronically ill patients with complex illnesses. Especially in the field of internistic rheumatology, interdisciplinary work is essential to consider the complex somatic and psychosocial aspects of a chronic illness. Nevertheless, the aspects of interprofessional work in the study of medicine and psychology are insufficiently addressed. For this reason, a model project for interdisciplinary university teaching was conceived, which combines both subjects. The course was held for the first time in semester 2019/2020 and was rated excellent by the participants. The main goal of the course is the implementation of interprofessional work in the training of medical personnel. In addition, the discipline of internistic rheumatology could be brought closer to the students.

Cardiovascular regulation: associations between exercise and head-up tilt.

It was hypothesized that faster cardiorespiratory kinetics during exercise are associated with higher orthostatic tolerance. Cardiorespiratory kinetics of 14 healthy male subjects (30 ± 4 years, 179 ± 8 cm, 79 ± 8 kg) were tested on a cycle ergometer during exercise with changing work rates of 30 and 80 W. Pulmonary oxygen uptake ( ) was measured breath-by-breath and heart rate (HR), mean arterial blood pressure (MAP), and total peripheral resistance (TPR) were measured beat-to-beat. Muscular oxygen uptake ( ) was estimated from HR and . Kinetic parameters were determined by time-series analysis, using cross-correlation functions (CCFmax(x)) between the parameter and the work rate. Cardiovascular regulations of MAP, HR, and TPR during orthostatic stress were measured beat-to-beat on a tilt seat. Changes between the minima and maxima during the 6° head-down tilt and the 90° head-up tilt positions were calculated for each parameter (Δtilt-up). correlated significantly with ΔTPRtilt-up (r = 0.790, p ≤ 0.001). CCFmax(HR) was significantly correlated with ΔHRtilt-up (r = -0.705, p = 0.002) and the amplitude in HR from 30 to 80 W (rSP = -0.574, p = 0.016). The observed correlations between cardiorespiratory regulation in response to exercise and orthostatic stress during rest might allow for a more differential analysis of the underlying mechanisms of orthostatic intolerance in, for example, patient groups.

Correction to: Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism.

The article Occlusion of left atrial appendage aff ects metabolomic profile:focus on glycolysis, tricarboxylic acid and urea metabolism, written by K. Sattler, M. Behnes, C. Barth, A. Wenke, B. Sartorius, I. El-Battrawy, K. Mashayekhi, J. Kuschyk, U. Hoffmann, T. Papavasiliu, C. Fastner, S. Baumann, S. Lang, X. Zhou, G. Yücel, M. BorggrefeI, Akin, was originally published Online First without open access.

Impact of 60 days of 6° head down tilt bed rest on muscular oxygen uptake and heart rate kinetics: efficacy of a reactive sledge jump countermeasure.

PURPOSE: The effects of 60 days of head down tilt bed rest (HDBR) with and without the application of a reactive jump countermeasure were investigated, using a method which enables to discriminate between pulmonary ([Formula: see text]O2pulm) and muscular ([Formula: see text]O2musc) oxygen uptake kinetics to control for hemodynamic influences. METHODS: 22 subjects were randomly allocated to either a group performing a reactive jumps countermeasure (JUMP; n = 11, male, 29 ± 7 years, 23.9 ± 1.3 kg m- 2) or a control group (CTRL; n = 11, male, 29 ± 6 years, 23.3 ± 2.0 kg m- 2). Heart rate (HR) and [Formula: see text]O2pulm were measured in response to repeated changes in work rate between 30 and 80 W before (BDC-9) and two times after HDBR (R+ 2, R+ 13). Kinetic responses of HR, [Formula: see text]O2pulm, and [Formula: see text]O2musc were assessed applying time series analysis. Higher maxima in cross-correlation functions (CCFmax(x)) between work rate and the respective parameter indicate faster kinetics responses. Statistical analysis was performed applying multifactorial analysis of variance. RESULTS: CCFmax([Formula: see text]O2musc) and CCFmax([Formula: see text]O2pulm) were not significantly different before and after HDBR (P > 0.05). CCFmax(HR) decreased following bed rest (JUMP: BDC-9: 0.30 ± 0.09 vs. R+ 2: 0.28 ± 0.06 vs. R+13: 0.28 ± 0.07; CTRL: 0.35 ± 0.09 vs. 0.27 ± 0.06 vs. 0.33 ± 0.07 P = 0.025). No significant differences between the groups were observed (P > 0.05). Significant alterations were found for CCFmax of mean arterial blood pressure (mBP) after HDBR (JUMP: BDC-9: 0.21 ± 0.07 vs. R+ 2: 0.30 ± 0.13 vs. R+ 13: 0.28 ± 0.08; CTRL: 0.25 ± 0.07 vs. 0.38 ± 0.13 vs. 0.28 ± 0.08; P = 0.008). CONCLUSIONS: Despite hemodynamic changes, [Formula: see text]O2 kinetics seem to be preserved for a longer period of HDBR, even without the application of a countermeasure.

Temporal dissociation between muscle and pulmonary oxygen uptake kinetics: influences of perfusion dynamics and arteriovenous oxygen concentration differences in muscles and lungs.

PURPOSE: The aim of the study was to test whether or not the arteriovenous oxygen concentration difference (avDO2) kinetics at the pulmonary (avDO2pulm) and muscle (avDO2musc) levels is significantly different during dynamic exercise. METHODS: A re-analysis involving six publications dealing with kinetic analysis was utilized with an overall sample size of 69 participants. All studies comprised an identical pseudorandom binary sequence work rate (WR) protocol-WR changes between 30 and 80 W-to analyze the kinetic responses of pulmonary ([Formula: see text]) and muscle ([Formula: see text]) oxygen uptake kinetics as well as those of avDO2pulm and avDO2musc. RESULTS: A significant difference between [Formula: see text] (0.395 ± 0.079) and [Formula: see text] kinetics (0.330 ± 0.078) was observed (p < 0.001), where the variables showed a significant relationship (rSP = 0.744, p < 0.001). There were no significant differences between avDO2musc (0.446 ± 0.077) and avDO2pulm kinetics (0.451 ± 0.075), which are highly correlated (r = 0.929, p < 0.001). CONCLUSION: It is suggested that neither avDO2pulm nor avDO2musc kinetic responses seem to be responsible for the differences between estimated [Formula: see text] and measured [Formula: see text] kinetics. Obviously, the conflation of avDO2 and perfusion ([Formula: see text] ) at different points in time and at different physiological levels drive potential differences in [Formula: see text] and [Formula: see text] kinetics. Therefore, [Formula: see text] should, in general, be considered whenever oxygen uptake kinetics are analyzed or discussed.

Non-invasive estimation of muscle oxygen uptake kinetics with pseudorandom binary sequence and step exercise responses.

PURPOSE: The aim of the study was to test for significant differences in non-invasively estimated muscle oxygen uptake ([Formula: see text]) kinetics, assessed by a square-wave exercise protocol (STEP) as well as by a time series approach with pseudorandom binary sequence (PRBS) work rate (WR) changes. METHODS: Seventeen healthy and active individuals (10 women, 7 men; 23 ± 2 years old; height 175 ± 11 cm; body mass 73 ± 14 kg [mean ± SD]) completed five repetitions of WR transitions from 30 to 80 W for the STEP approach and two sequences of pseudorandom binary WR changes between 30 and 80 W for the PRBS approach. Pulmonary oxygen uptake ([Formula: see text]) was measured breath by breath. [Formula: see text] kinetics were estimated during phase II [Formula: see text] in the STEP approach and during the pseudorandom binary sequence WR changes in the PRBS approach. RESULTS: No significant differences were observed between different models of the STEP and the PRBS approach for estimation of [Formula: see text] kinetics (p > 0.05). In addition, a very high variability between the models was determined for [Formula: see text] kinetics [mean time constants (τ) difference: - 2.5 ± 11.4 s]. A significant correlation for τ of [Formula: see text] between the STEP approach with experimentally determined phase I [Formula: see text] lengths and the PRBS approach was noticed (r = 0.536; p < 0.05). CONCLUSIONS: Both approaches (STEP and PRBS) are not significantly different for estimating the [Formula: see text] kinetics, but the very high variability impairs the predictability between the models. However, the determination of the length of phase I [Formula: see text] should be as appropriate as possible because predefined duration lengths can result in overestimations in [Formula: see text] kinetics.

Hypotension due to spinal anesthesia influences fetal circulation in primary caesarean sections.

PURPOSE: Hypotension due to spinal anesthesia is a well-known side effect in pregnant women receiving caesarean section. Little is known about its impact on fetal blood circulation. METHODS: 40 women with uncomplicated singleton term pregnancies prepared for caesarean section were prospectively evaluated by Doppler sonography before and immediately after spinal anesthesia. RESULTS: In 90% of the women, blood pressure significantly decreased after spinal anesthesia and 42.5% of the patients suffered from severe hypotension. We found a significant negative correlation between maternal blood pressure change and the resistant index (RI) of the umbilical artery (rs = - 0.376, p = 0.017) and a significant positive correlation between maternal blood pressure and fetal middle cerebral artery. CONCLUSION: Healthy fetuses seem to compensate well in situations with decreased uteroplacental blood flow due to maternal hypotension measured by means of RI changes in the fetal umbilical and middle cerebral artery. This raises the question if growth-restricted and/or preterm fetuses are able to compensate similarly or if general anesthesia would be a method of choice.

[Pregnancy Rhinitis - an Update]. / Update Schwangerschaftsrhinitis.

Pregnancy rhinitis (PR), a common condition in pregnant women, is defined as long-lasting nasal congestion due to mucosal swelling and increased secretion without any signs of infection, allergy or tumor, starting at any time during pregnancy and disappearing within 2 weeks of delivery. Smoking and a sensitization to house dust mites are known risk factors. While a definitive pathophysiological concept for PR does not exist, hormonal influences are discussed. We present a stepwise therapeutic strategy for PR and an overview to the latest literature.

[Blood pressure targets : The lower the better does not suit all]. / Blutdruckzielwerte : Je niedriger, desto besser ist nicht für alle Patienten gut.

BACKGROUND: The systolic blood pressure intervention trial (SPRINT) published in 2015 has opened up new discussions on whether a lower blood pressure target as recommended by the current guidelines would be better for some patient groups. OBJECTIVES: To review patient groups in which lower blood pressure targets would not be better. MATERIALS AND METHODS: The results of SPRINT, its post-hoc and subgroup analyses, other studies and newer studies, as well as metaanalyses on the topic of blood pressure targets are reviewed and discussed. Studies with patients excluded from the SPRINT study were also analysed. The current international guidelines and recommendations of the Deutsche Hochdruckliga e. V. DHL® are included. RESULTS: Blood pressure monitoring methods differed considerably in the previously published studies. The low blood pressure value in SPRINT was mainly achieved due to the unusual method of blood pressure monitoring used and, as such, cannot be compared with blood pressure values in other studies. Based on current evidence, "the lower the better" should not be recommended in the following patient groups: older patients, in particular infirm older patients, patients with diabetes, patients without coronary heart disease or with low cardiovascular risk. CONCLUSIONS: When determining a blood pressure target, the method of blood pressure monitoring should be defined. A lower blood pressure target has been shown to be better in some well defined patient groups. However, adverse events due to antihypertensive medications should always be taken into account. Given the multiple exclusion criteria in trials and the results of many studies, "new" lower blood pressure targets could not be recommended in a large population of patients.

Response Evaluation in Head and Neck Oncology: Definition and Prediction.

Curative treatment of head and neck squamous cell carcinoma includes surgery and/or (chemo)radiation, whereas in the palliative setting, chemotherapy and/or immunotherapy represent(s) the standard approach. With regard to quality control, methods for determining treatment response are sorely needed. For surgical therapy, histopathology is the standard quality control. Established criteria for high-risk patients include resection margins of the primary tumor and extracapsular extension of lymph node metastases. After definitive chemoradiation, treatment response is generally evaluated by tomographic imaging combined with endoscopy including re-biopsy of the tumor region. Single-cycle induction chemotherapy may be used to determine the radiosensitivity of tumors, helping to define surgical and nonsurgical treatment options. Innovative approaches with implications for prognosis include the analysis of immune infiltrates, liquid biopsy, molecular characterization (proteomics, genomics), molecular and functional imaging (PET-CT, PET-MRI), as well as advanced imaging data analysis (radio[geno]mics/texture analysis). Human papilloma virus, as a prognostically relevant parameter, is currently being investigated for de-escalation strategies. With regard to the extended personalization of oncologic therapy, markers predicting treatment response are desirable and seem to be important, also from a socioeconomic perspective.

[Pregnancy Rhinitis - an Update]. / Update Schwangerschaftsrhinitis.

Pregnancy rhinitis (PR), a common condition in pregnant women, is defined as long-lasting nasal congestion due to mucosal swelling and increased secretion without any signs of infection, allergy or tumor, starting at any time during pregnancy and disappearing within 2 weeks of delivery. Smoking and a sensitization to house dust mites are known risk factors. While a definitive pathophysiological concept for PR does not exist, hormonal influences are discussed. We present a stepwise therapeutic strategy for PR and an overview to the latest literature.

Allergic manifestation 15 years after early intervention with hydrolyzed formulas--the GINI Study.

BACKGROUND: Data on the long-term impact of hydrolyzed formulas on allergies are scarce. OBJECTIVE: To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence. METHODS: GINI trial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent-reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models. RESULTS: Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (risk ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group on any manifestation,nor was there an effect on sensitization with any formula. CONCLUSION: In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence.

V̇O2 and HR kinetics before and after International Space Station missions.

PURPOSE: Heart rate (HR), pulmonary and muscle oxygen uptake ([Formula: see text]O2pulm, [Formula: see text]O2musc) kinetics after changes of work rate (WR) indicate regulatory characteristics related to aerobic metabolism. We analysed whether the kinetics of HR, [Formula: see text]O2pulm and [Formula: see text]O2musc are slowed after missions to the International Space Station (ISS). The changes of the kinetics were correlated with [Formula: see text]O2peak data. METHODS: 10 astronauts [4 females, 6 males, age: 48.0 ± 3.8 years, height: 176 ± 7 cm, mass: 74.5 ± 15.9 kg (mean ± SD)] performed an incremental test to determine [Formula: see text]O2peak (before missions on L-110 days, after return on R+1/+10/+36 days), and a cardio-respiratory kinetics test (CRKT) with randomized 30-80 W WR changes to determine HR, [Formula: see text]O2pulm and [Formula: see text]O2musc kinetics by time-series analysis (L-236/-73, R+6/+21). Kinetics were summarized by maximum and related lag of cross-correlation function (CCFmax, CCFlag) of WR with the analysed parameter. RESULTS: Statistically, significant changes were also found for CCFmax([Formula: see text]O2musc) between L-236 and R+6 (P = 0.010), L-236 and R+21 (P = 0.030), L-72 and R+6 (P = 0.043). Between pre-to-post mission change in [Formula: see text]O2peak and CCFmax(HR), a correlation was shown (r SP = 0.67, P = 0.017). CONCLUSION: The [Formula: see text]O2musc kinetics changes indicate aerobic detraining effects which are present up to 21 days following space flight. The correlations between changes in [Formula: see text]O2peak and HR kinetics illustrate the key role of cardiovascular regulation in [Formula: see text]O2peak. The addition of CRKT to ISS flight is recommended to obtain information regarding the potential muscular and cardiovascular deconditioning. This allows a reduction in the frequency of higher intensity testing during flight.

Analysis of cardio-pulmonary and respiratory kinetics in different body positions: impact of venous return on pulmonary measurements.

PURPOSE: The aim of the study was to compare the kinetics responses of heart rate (HR), pulmonary ([Formula: see text]O2pulm), and muscular ([Formula: see text]O2musc) oxygen uptake during dynamic leg exercise across different body positions (-6°, 45°, and 75°). METHODS: Ten healthy individuals [six men, four women; age 23.4 ± 2.8 years; height 179.7 ± 8.3 cm; body mass 73 ± 12 kg (mean ± SD)] completed pseudo-random binary sequence (PRBS) work rate (WR) changes between 30 and 80 W in each posture. HR was measured beat-to-beat by echocardiogram and [Formula: see text]O2pulm by breath-by-breath gas exchange. [Formula: see text]O2musc kinetics were assessed by the procedure of Hoffmann et al. (Eur J Appl Physiol 113:1745-1754, 2013) applying a circulatory model and cross-correlation functions (CCF). RESULTS: For [Formula: see text]O2pulm kinetics significant differences between -6° (CCF-values: 0.292 ± 0.040) and 45° (0.256 ± 0.034; p < 0.01; n = 10) as well as between -6° and 75° (0.214 ± 0.057; p < 0.05; n = 10) were detected at lag '40 s' of the CCF course as interaction effects (factors: Lag × Posture). HR and [Formula: see text]O2musc kinetics yield no significant differences across the postures. CONCLUSIONS: The analysis of cardio-dynamic and respiratory kinetics, especially with an emphasis on muscular and cellular level, has to consider venous return and cardiac output distortions. Simplified observations of kinetics responses resulting in time constants and time delays only should be replaced by the time-series analysis for a more sophisticated evaluation. The results illustrate that isolated [Formula: see text]O2pulm measurements without cardio-dynamic influences may not represent the kinetics responses originally revealed at muscular level.

Outcomes of anatomical vs. functional testing for coronary artery disease : Lessons from the PROMISE trial.

The development of coronary artery disease (CAD) is a major, final common pathway in heart disease worldwide. With a rise in stress testing and increased scrutiny on cost-effectiveness and radiation exposure in medical imaging, a focus on the relative merits of anatomic versus functional characterization of CAD has emerged. In this context, coronary computed tomography angiography (CCTA) is a noninvasive alternative to functional testing as a first-line test for CAD detection but is complimentary in its nature. Here, we discuss the design, results, and implications of the PROMISE trial, a randomized comparative effectiveness study of 10,003 patients across 193 sites in the United States and Canada comparing the prognostic and diagnostic power of CCTA and standard stress testing. Specifically, we discuss the safety (e. g., contrast, radiation exposure) of CCTA versus functional testing in CAD, the need for improved selection for noninvasive testing, the frequency of downstream testing after anatomic or functional imaging, the use of imaging results in clinical management, and novel modalities of CAD risk determination using CCTA. PROMISE demonstrated that in a real-world, low-to-intermediate risk patient population referred to noninvasive testing for CAD, both CCTA and functional testing approaches have similar clinical, economic, and safety-based outcomes. We conclude with open questions in CAD imaging, specifically as they pertain to the utilization of CCTA.

Cardiorespiratory Kinetics Determined by Pseudo-Random Binary Sequences - Comparisons between Walking and Cycling.

This study aims to compare cardiorespiratory kinetics as a response to a standardised work rate protocol with pseudo-random binary sequences between cycling and walking in young healthy subjects. Muscular and pulmonary oxygen uptake (V̇O2) kinetics as well as heart rate kinetics were expected to be similar for walking and cycling. Cardiac data and V̇O2 of 23 healthy young subjects were measured in response to pseudo-random binary sequences. Kinetics were assessed applying time series analysis. Higher maxima of cross-correlation functions between work rate and the respective parameter indicate faster kinetics responses. Muscular V̇O2 kinetics were estimated from heart rate and pulmonary V̇O2 using a circulatory model. Muscular (walking vs. cycling [mean±SD in arbitrary units]: 0.40±0.08 vs. 0.41±0.08) and pulmonary V̇O2 kinetics (0.35±0.06 vs. 0.35±0.06) were not different, although the time courses of the cross-correlation functions of pulmonary V̇O2 showed unexpected biphasic responses. Heart rate kinetics (0.50±0.14 vs. 0.40±0.14; P=0.017) was faster for walking. Regarding the biphasic cross-correlation functions of pulmonary V̇O2 during walking, the assessment of muscular V̇O2 kinetics via pseudo-random binary sequences requires a circulatory model to account for cardio-dynamic distortions. Faster heart rate kinetics for walking should be considered by comparing results from cycle and treadmill ergometry.