Effects of inspiratory muscle training on exertional breathlessness in patients with unilateral diaphragm dysfunction: a randomised trial.

Background: Unilateral diaphragm dysfunction (UDD) is an underdiagnosed cause of dyspnoea. Inspiratory muscle training (IMT) is the only conservative treatment for UDD, but the mechanisms of improvement are unknown. We characterised the effects of IMT on dyspnoea, exercise tolerance and respiratory muscle function in people with UDD. Methods: 15 people with UDD (73% male, 61±8 years) were randomised to 6 months of IMT (50% maximal inspiratory mouth pressure (PI,max), n=10) or sham training (10% PI,max, n=5) (30 breaths twice per day). UDD was confirmed by phrenic nerve stimulation and persisted throughout the training period. Symptoms were assessed by the transitional dyspnoea index (TDI) and exercise tolerance by constant-load cycle tests performed pre- and post-training. Oesophageal (Pes) and gastric (Pga) pressures were measured with a dual-balloon catheter. Electromyography (EMG) and oxygenation (near-infrared spectroscopy) of respiratory muscles were assessed continuously during exercise. Results: The IMT group (from 45±6 to 62±23% PI,max) and sham group (no progression) completed 92 and 86% of prescribed sessions, respectively. PI,max, TDI scores and cycle endurance time improved significantly more after IMT versus sham (mean between-group differences: 28 (95% CI 13-28) cmH2O, 3.0 (95% CI 0.9-5.1) points and 6.0 (95% CI 0.4-11.5) min, respectively). During exercise at iso-time, Pes, Pga and EMG of the scalene muscles were reduced and the oxygen saturation indices of the scalene and abdominal muscles were higher post- versus pre-training only in the IMT group (all p<0.05). Conclusion: The effects of IMT on dyspnoea and exercise tolerance in UDD were not mediated by an improvement in isolated diaphragm function, but may reflect improvements in strength, coordination and/or oxygenation of the extra-diaphragmatic respiratory muscles.

Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable-polymer coronary stent - five-year results of the TARGET All Comers randomised clinical trial.

BACKGROUND: In the prospective, multicentre, randomised TARGET All Comers study, percutaneous coronary intervention (PCI) with the FIREHAWK biodegradable-polymer sirolimus-eluting stent (BP-SES) was non-inferior to the durable-polymer everolimus-eluting stent (DP-EES) for the primary endpoint of target lesion failure (TLF) at 12 months. AIMS: We aimed to report the final study outcomes at 5 years. METHODS: Patients referred for PCI were randomised to receive either a BP-SES or DP-EES in a 1:1 ratio in 10 European countries. Randomisation was stratified by centre and ST-elevation myocardial infarction (STEMI) presentation, and clinical follow-up extended to 5 years. The primary endpoint was TLF (composite of cardiac death, target vessel myocardial infarction [MI], or ischaemia-driven target lesion revascularisation). Secondary endpoints included patient-oriented composite events (POCE; composite of all-cause death, all MI, or any revascularisation and its components). RESULTS: From December 2015 to October 2016, 1,653 patients were randomly assigned to the BP-SES or DP-EES groups, of which 93.8% completed 5-year clinical follow-up or were deceased. At 5 years, TLF occurred in 17.1% of the BP-SES group and in 16.3% of the DP-EES group (p=0.68). POCE occurred in 34.0% of the BP-SES group and 32.7% of the DP-EES group (p=0.58). Revascularisation was the most common POCE, occurring in 19.3% of patients receiving BP-SES and 19.2% receiving DP-EES, of which less than one-third was ischaemia-driven target lesion-related. In the landmark analysis, there were no differences in the rates of TLF and POCE between groups from 1 to 5 years, and these results were consistent across all subgroups. CONCLUSIONS: In an all-comers population requiring stent implantation for myocardial ischaemia, the BP-SES was non-inferior to the DP-EES for the primary endpoint of TLF at 12 months, and results were sustained at 5 years, confirming the long-term safety and efficacy of the FIREHAWK BP-SES.

Long-term clinical outcomes of excimer laser coronary atherectomy for the management of recurrent in-stent restenosis.

BACKGROUND: Recurrent in-stent restenosis (ISR) remains a serious problem. Optimal modification of the underlying mechanism during index percutaneous coronary intervention (PCI) is key to prevent ISR. Excimer laser coronary atherectomy (ELCA) has its own indications and is among others used in recurrent ISR in case of stent underexpansion and/or diffuse neointimal hyperplasia. We aimed to assess the long-term clinical outcomes of ELCA for the management of recurrent ISR. METHODS: A multicenter, retrospective observational study was conducted. Patients with recurrent ISR who were additionally treated with ELCA were included. The primary outcome was major adverse cardiac events (MACE) defined as a composite of cardiovascular death, myocardial infarction, stroke, target lesion revascularization at 12 months, and longer term. RESULTS: Between 2014 and 2022, 51 patients underwent PCI with the additional use ELCA for recurrent ISR. Primary outcome occurred in 6 patients (11.8%) at 12 months and in 12 patients (23.5%) at a median follow-up of 4 (1-6) years. Technical and procedural success were achieved in 92% and 90% of cases, respectively. Coronary perforation occurred in 2 patients as a result of distal wire perforation, but was not ELCA-related. There were no in-hospital MACE. CONCLUSIONS: ELCA appears to be a safe method with acceptable long-term results for the management of recurrent ISR.

A Randomized Controlled Trial Comparing BioMime Sirolimus-Eluting Stent With Everolimus-Eluting Stent: Two-Year Outcomes of the meriT-V Trial.

Background: Drug-eluting stents (DESs) based on biodegradable polymers (BPs) have been introduced to reduce the risk for late and very late stent thrombosis (ST), which were frequently observed with earlier generations of DES designs based on durable polymers (DPs); however, randomized controlled trials on these DES designs are scarce. The meriT-V trial is a randomized, active-controlled, non-inferiority trial with a prospective, multicenter design that evaluated the 2-year efficacy of a novel third-generation, ultra-thin strut, BP-based BioMime sirolimus-eluting stent (SES) versus the DP-based XIENCE everolimus-eluting stent (EES) for the treatment of de novo lesions. Methods: The meriT-V is a randomized trial that enrolled 256 patients at 15 centers across Europe and Brazil. Here, we report the outcomes of the extended follow-up period of 2 years. The randomization of enrolled patients was in a 2:1 ratio; the enrolled patients received either the BioMime SES (n = 170) or the XIENCE EES (n = 86). The three-point major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction (MI), or ischemia-driven target vessel revascularization (ID-TVR), was considered as the composite safety and efficacy endpoint. Ischemia-driven target lesion revascularization (ID-TLR) was evaluated as well as the frequency of definite/probable ST, based on the first Academic Research Consortium definitions. Results: The trial had a 2-year follow-up completion rate of 98.44% (n = 252/256 patients), and the clinical outcomes assessment showed a nonsignificant difference in the cumulative rate of three-point MACE between both arms (BioMime vs. XIENCE: 7.74% vs. 9.52%, P = 0.62). Even the MI incidences in the BioMime arm were insignificantly lower than those of the XIENCE arm (1.79% vs. 5.95%, P = 0.17). Late ST was observed in 1.19% cases of the XIENCE arm, while there were no such cases in the BioMime arm (P = 0.16). Conclusions: The objective comparisons between the novel BP-based BioMime SES and the well-established DP-based XIENCE EES in this randomized controlled trial show acceptable outcomes of both the devices in the cardiac deaths, MI, ID-TVR, and ST. Moreover, since there were no incidences of cardiac death in the entire study sample over the course of 2 years, we contend that the findings of the study are highly significant for both these DES designs. In this preliminary comparative trial, the device safety of BioMime SES can be affirmed to be acceptable, considering the lower three-point MACE rate and absence of late ST in the BioMime arm over the 2-year period.

A randomized controlled trial comparing BioMime Sirolimus-Eluting Stent with Everolimus-Eluting Stent: two-year outcomes of the meriT-V trial

BACKGROUND: Drug-eluting stents (DESs) based on biodegradable polymers (BPs) have been introduced to reduce the risk for late and very late stent thrombosis (ST), which were frequently observed with earlier generations of DES designs based on durable polymers (DPs); however, randomized controlled trials on these DES designs are scarce. The meriT-V trial is a randomized, active-controlled, non-inferiority trial with a prospective, multicenter design that evaluated the 2-year efficacy of a novel third-generation, ultra-thin strut, BP-based BioMime sirolimus-eluting stent (SES) versus the DP-based XIENCE everolimus-eluting stent (EES) for the treatment of de novo lesions. METHODS: The meriT-V is a randomized trial that enrolled 256 patients at 15 centers across Europe and Brazil. Here, we report the outcomes of the extended follow-up period of 2 years. The randomization of enrolled patients was in a 2:1 ratio; the enrolled patients received either the BioMime SES (n = 170) or the XIENCE EES (n = 86). The three-point major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction (MI), or ischemia-driven target vessel revascularization (ID-TVR), was considered as the composite safety and efficacy endpoint. Ischemia-driven target lesion revascularization (ID-TLR) was evaluated as well as the frequency of definite/probable ST, based on the first Academic Research Consortium definitions. RESULTS: The trial had a 2-year follow-up completion rate of 98.44% (n = 252/256 patients), and the clinical outcomes assessment showed a nonsignificant difference in the cumulative rate of three-point MACE between both arms (BioMime vs. XIENCE: 7.74% vs. 9.52%, P = 0.62). Even the MI incidences in the BioMime arm were insignificantly lower than those of the XIENCE arm (1.79% vs.

iFR/FFR/IVUS Discordance and Clinical Implications: Results From the Prospective Left Main Physiology Registry.

OBJECTIVES: This study aimed to assess discordance between results of instantaneous wave-free ratio (iFR), fractional flow reserve (FFR), and intravascular ultrasound (IVUS) in intermediate left main coronary (LM) lesions, and its impact on clinical decision making and outcome. METHODS: We enrolled 250 patients with a 40%-80% LM stenosis in a prospective, multicenter registry. These patients underwent both iFR and FFR measurements. Of these, 86 underwent IVUS and assessment of the minimal lumen area (MLA), with a 6 mm2 cutoff for significance. RESULTS: Isolated LM disease was recognized in 95 patients (38.0%), while 155 patients (62.0%) had both LM disease and downstream disease. In 53.2% of iFR+ and 56.7% of FFR+ LM lesions, the measurement was positive in only one daughter vessel. iFR/FFR discordance occurred in 25.0% of patients with isolated LM disease and 36.2% of patients with concomitant downstream disease (P=.049). In patients with isolated LM disease, discordance was significantly more common in the left anterior descending artery and younger age was an independent predictor of iFR-/FFR+ discordance. iFR/MLA and FFR/MLA discordance occurred in 37.0% and 29.4%, respectively. Within 1 year of follow-up, major cardiac adverse events (MACE) occurred in 8.5% and 9.7% (P=.763) of patients whose LM lesion was deferred or revascularized, respectively. Discordance was not an independent predictor of MACE. CONCLUSIONS: Current methods of estimating LM lesion significance often yield discrepant findings, complicating therapeutic decision-making.

Characterization of rheumatic heart disease from electrocardiogram recordings.

Objective. Rheumatic Heart Disease (RHD) is one of the highly prevalent heart diseases in developing countries that can affect the pericardium, myocardium, or endocardium. Rheumatic endocarditis is a common RHD variant that gradually deteriorates the normal function of the heart valves. RHD can be diagnosed using standard echocardiography or listened to as a heart murmur using a stethoscope. The electrocardiogram (ECG), on the other hand, is critical in the study and identification of heart rhythms and abnormalities. The effectiveness of ECG to identify distinguishing signs of rheumatic heart problems, however, has not been adequately examined. This study addressed the possible use of ECG recordings for the characterization of problems of the heart in RHD patients.Approach. To this end, an extensive ECG dataset was collected from patients suffering from RHD (PwRHD), and healthy control subjects (HC). Bandpass filtering was used at the preprocessing stage. Each data was then standardized by removing its mean and dividing by its standard deviation. Delineation of the onsets and offsets of waves was performed using KIT-IBT open ECG MATLAB toolbox. PR interval, QRS duration, RR intervals, QT intervals, and QTc intervals were computed for each heartbeat. The median values of the temporal parameters were used to eliminate possible outliers due to missed ECG waves. The data were clustered in different age groups and sex. Another categorization was done based on the time duration since the first RHD diagnosis.Main results. In 47.2% of the cases, a PR elongation was observed, and in 26.4% of the cases, the QRS duration was elongated. QTc was elongated in 44.3% of the cases. It was also observed that 62.2% of the cases had bradycardia.Significance. The end product of this research can lead to new medical devices and services that can screen RHD based on ECG which could somehow assist in the detection and diagnosis of the disease in low-resource settings and alleviate the burden of the disease.

Grey wolf genomic history reveals a dual ancestry of dogs.

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1-8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.

Impact of proton pump inhibitors on efficacy of antiplatelet strategies with ticagrelor or aspirin after percutaneous coronary intervention: Insights from the GLOBAL LEADERS trial.

BACKGROUND: Several studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events. AIMS: We aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI). METHODS: This is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with the reference arm (12-month aspirin monotherapy following 12-month DAPT) after PCI. Patient-oriented composite endpoints (POCEs: all-cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time-dependent covariate in patients with the experiment or reference antiplatelet arm. RESULTS: Among 15,839 patients, 2115 patients (13.5%) experienced POCE at 2 years. In the reference arm, the use of PPIs was independently associated with POCE (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.12-1.44) and its individual components, whereas it was not in the experimental arm (HR: 1.04; 95% CI: 0.92-1.19; pinteraction = 0.035). During the second-year follow-up, patients taking aspirin with PPIs had a significantly higher risk of POCE compared to those on aspirin without PPIs (HR: 1.57; 95% CI: 1.27-1.94), whereas the risk did not differ significantly irrespective of PPI in ticagrelor monotherapy group (HR: 1.03; 95% CI: 0.83-1.28; pinteraction = 0.008). CONCLUSIONS: In contrast to conventional antiplatelet strategy, there were no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events, which should be confirmed in further studies. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov.

Lipid-lowering therapy and risk-based LDL-C goal attainment in Belgium: DA VINCI observational study.

BACKGROUND: Cardiovascular disease (CVD) is one of the leading causes of death in Belgium. Current strategies for the prevention and management of CVD focus on reducing low-density lipoprotein cholesterol (LDL-C) levels. This analysis assessed whether LDL-C goals, recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines, were being achieved in a Belgian study population. METHODS: The cross-sectional, observational, DA VINCI study enrolled patients prescribed lipid-lowering therapy (LLT) between 21 June 2017 and 20 November 2018. Data for patients from Belgium were extracted for this country-specific analysis. Primary endpoint was the proportion of patients who achieved 2016 ESC/EAS risk-based LDL-C goals; attainment of 2019 risk-based LDL-C goals was evaluated post hoc. RESULTS: Of 497 enrolled patients, 41% were female and mean age was 68 years. Among subjects with an LDL-C measurement on stabilised LLT, moderate-intensity statin monotherapy was the most prescribed LLT regimen (59%). Overall, 63% of patients achieved their risk-based LDL-C goals according to the 2016 ESC/EAS guidelines. Among patients with established ASCVD, risk-based LDL-C goal attainment was higher in patients with peripheral arterial disease (53%) than patients with coronary (37%) and cerebrovascular disease (42%). According to the updated 2019 ESC/EAS guidelines, less than half (41%) of patients achieved their risk-based LDL-C goal. The proportion of primary and secondary prevention patients who achieved 2019 risk-based LDL-C goals was 59% and 18%, respectively. CONCLUSION: These findings reveal a large gap between the LDL-C goals advocated by the ESC/EAS and the levels achieved in routine clinical practice in Belgium.

Ticagrelor Monotherapy or Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation: Per-Protocol Analysis of the GLOBAL LEADERS Trial.

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention-to-treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention-to-treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per-protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time-varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all-cause mortality or nonfatal Q-wave myocardial infarction at 2 years. At 2-year follow-up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per-protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75-1.03; P=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79-1.26; P=0.99). The per-protocol and intention-to-treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Angiography-derived physiology guidance vs usual care in an All-comers PCI population treated with the healing-targeted supreme stent and Ticagrelor monotherapy: PIONEER IV trial design.

BACKGROUND: Current ESC guidelines recommend the use of intra-coronary pressure guidewires for functional assessment of intermediate-grade coronary stenoses. Angiography-derived quantitative flow ratio (QFR) is a novel method of assessing these stenoses, and guiding percutaneous coronary intervention (PCI). METHODS/DESIGN: The PIONEER IV trial is a prospective, all-comers, multi-center trial, which will randomize 2,540 patients in a 1:1 ratio to PCI guided by angiography-derived physiology or usual care, with unrestricted use in both arms of the Healing-Targeted Supreme sirolimus-eluting stent (HT Supreme). The stent's fast, biologically healthy, and robust endothelial coverage allows for short dual-antiplatelet therapy (DAPT); hence the antiplatelet regimen of choice is 1-month DAPT, followed by ticagrelor monotherapy. In the angiography-derived physiology guided arm, lesions will be functionally assessed using on-line QFR, with stenting indicated in lesions with a QFR ≤0.80. Post-stenting, QFR will be repeated in the stented vessel(s), with post-dilatation or additional stenting recommended if the QFR<0.91 distal to the stent, or if the delta QFR (across the stent) is >0.05. Usual care PCI is performed according to standard clinical practice. The primary endpoint is a non-inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any clinically, and physiologically driven revascularization with a non-inferiority risk-difference margin of 3.2%, at 1-year post-procedure. Clinical follow-up will be up to 3 years. SUMMARY: The PIONEER IV trial aims to demonstrate non-inferiority of QFR-guided PCI to usual care PCI with respect to POCE at 1-year in patients treated with HT Supreme stents and ticagrelor monotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov UNIQUE IDENTIFIER: NCT04923191 CLASSIFICATIONS: Interventional Cardiology.

PRECISE-DAPT score for bleeding risk prediction in patients on dual or single antiplatelet regimens: insights from the GLOBAL LEADERS and GLASSY.

AIMS: The five-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally adjudicated bleeding endpoints. METHODS AND RESULTS: The PRECISE-DAPT was calculated in 14 928 and 7134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict Bleeding Academic Research Consortium 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally adjudicated in GLOBAL LEADERS and GLASSY, respectively. At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 [95% confidence interval (CI): 0.63-0.71] vs. 0.63 (95% CI: 0.59-0.67) in GLOBAL LEADERS (P = 0.27), and 0.67 (95% CI: 0.61-0.73) vs. 0.66 (95% CI: 0.61-0.72) in GLASSY (P = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified four-item PRECISE-DAPT. CONCLUSION: The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints.

Can Heart Sound Denoising be Beneficial in Phonocardiogram Classification Tasksƒ.

The purpose of computer-aided diagnosis (CAD) systems is to improve the detection of diseases in a shorter time and with reduced subjectivity. A robust system frequently requires a noise-free input signal. For CADs which use heart sounds, this problem is critical as heart sounds are often low amplitude and affected by some unavoidable sources of noise such as movement artifacts and physiological sounds. Removing noises by using denoising algorithms can be beneficial in improving the diagnostics accuracy of CADs. In this study, four denoising algorithms were investigated. Each algorithm has been carefully adapted to fit the requirements of the phonocardiograph signal. The effect of the denoising algorithms was objectively compared based on the improvement it introduces in the classification performance of the heart sound dataset. According to the findings, using denoising methods directly before classification decreased the algorithm's classification performance because a murmur was also treated as noise and suppressed by the denoising process. However, when denoising using Wiener estimation-based spectral subtraction was used as a preprocessing step to improve the segmentation algorithm, it increased the system's classification performance with a sensitivity of 96.0%, a specificity of 74.0%, and an overall score of 85.0%. As a result, to improve performance, denoising can be added as a preprocessing step into heart sound classifiers that are based on heart sound segmentation.

Steering Does Affect Biophysical Responses in Asynchronous, but Not Synchronous Submaximal Handcycle Ergometry in Able-Bodied Men.

Real-life daily handcycling requires combined propulsion and steering to control the front wheel. Today, the handcycle cranks are mostly mounted synchronously unlike the early handcycle generations. Alternatively, arm cycle ergometers do not require steering and the cranks are mostly positioned asynchronously. The current study aims to evaluate the effects of combining propulsion and steering requirements on synchronous and asynchronous submaximal handcycle ergometry. We hypothesize that asynchronous handcycling with steering results in the mechanically least efficient condition, due to compensation for unwanted rotations that are not seen in synchronous handcycling, regardless of steering. Sixteen able-bodied male novices volunteered in this lab-based experiment. The set-up consisted of a handcycle ergometer with 3D force sensors at each crank that also allows "natural" steering. Four submaximal steady-state (60 rpm, ~35 W) exercise conditions were presented in a counterbalanced order: synchronous with a fixed steering axis, synchronous with steering, asynchronous with a fixed axis and asynchronous with steering. All participants practiced 3 × 4 mins with 30 mins rest in between every condition. Finally, they did handcycle for 4 mins in each of the four conditions, interspaced with 10 mins rest, while metabolic outcomes, kinetics and kinematics of the ergometer were recorded. The additional steering component did not influence velocity, torque and power production during synchronous handcycling and therefore resulted in an equal metabolically efficient handcycling configuration compared to the fixed condition. Contrarily, asynchronous handcycling with steering requirements showed a reduced mechanical efficiency, as velocity around the steering axis increased and torque and power production were less effective. Based on the torque production around the crank and steering axes, neuromuscular compensation strategies seem necessary to prevent steering movements in the asynchronous mode. To practice or test real-life daily synchronous handcycling, a synchronous crank set-up of the ergometer is advised, as exercise performance in terms of mechanical efficiency, metabolic strain, and torque production is independent of steering requirements in that mode. Asynchronous handcycling or arm ergometry demands a different handcycle technique in terms of torque production and results in higher metabolic responses than synchronous handcycling, making it unsuitable for testing.

Rheumatic Heart Disease Screening Based on Phonocardiogram.

Rheumatic heart disease (RHD) is one of the most common causes of cardiovascular complications in developing countries. It is a heart valve disease that typically affects children. Impaired heart valves stop functioning properly, resulting in a turbulent blood flow within the heart known as a murmur. This murmur can be detected by cardiac auscultation. However, the specificity and sensitivity of manual auscultation were reported to be low. The other alternative is echocardiography, which is costly and requires a highly qualified physician. Given the disease's current high prevalence rate (the latest reported rate in the study area (Ethiopia) was 5.65%), there is a pressing need for early detection of the disease through mass screening programs. This paper proposes an automated RHD screening approach using machine learning that can be used by non-medically trained persons outside of a clinical setting. Heart sound data was collected from 124 persons with RHD (PwRHD) and 46 healthy controls (HC) in Ethiopia with an additional 81 HC records from an open-access dataset. Thirty-one distinct features were extracted to correctly represent RHD. A support vector machine (SVM) classifier was evaluated using two nested cross-validation approaches to quantitatively assess the generalization of the system to previously unseen subjects. For regular nested 10-fold cross-validation, an f1-score of 96.0 ± 0.9%, recall 95.8 ± 1.5%, precision 96.2 ± 0.6% and a specificity of 96.0 ± 0.6% were achieved. In the imbalanced nested cross-validation at a prevalence rate of 5%, it achieved an f1-score of 72.2 ± 0.8%, recall 92.3 ± 0.4%, precision 59.2 ± 3.6%, and a specificity of 94.8 ± 0.6%. In screening tasks where the prevalence of the disease is small, recall is more important than precision. The findings are encouraging, and the proposed screening tool can be inexpensive, easy to deploy, and has an excellent detection rate. As a result, it has the potential for mass screening and early detection of RHD in developing countries.

Efficacy and Safety of Ticagrelor Monotherapy by Clinical Presentation: Pre-Specified Analysis of the GLOBAL LEADERS Trial.

Background The optimal duration of dual antiplatelet therapy after coronary drug-eluting stent placement in adults with stable coronary artery disease (SCAD) versus acute coronary syndromes (ACS) remains uncertain. Methods and Results This was a prespecified subgroup analysis of the GLOBAL LEADERS trial. Participants were randomly assigned 1:1 to the experimental or reference strategy, stratified by ACS (experimental, n=3750; reference, n=3737) versus SCAD (experimental, n=4230; reference, n=4251). The experimental strategy was 75 to 100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy. The reference strategy was 75 to 100 mg aspirin daily plus either 75 mg clopidogrel daily (for SCAD) or 90 mg ticagrelor twice daily (for ACS) for 12 months, followed by aspirin monotherapy for 12 months. The primary end point at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction. The key secondary safety end point was site-reported Bleeding Academic Research Consortium grade 3 or 5 bleeding. The primary end point occurred in 147 (3.92%) versus 169 (4.52%) patients with ACS (rate ratio [RR], 0.86; 95% CI, 0.69-1.08; P=0.189), and in 157 (3.71%) versus 180 (4.23%) patients with SCAD (RR, 0.87; 95% CI, 0.71-1.08; P=0.221) with experimental and reference strategy, respectively (P-interaction=0.926). Bleeding Academic Research Consortium grade 3 or 5 bleeding occurred in 73 (1.95%) versus 100 (2.68%) patients with ACS (RR, 0.73; 95% CI, 0.54-0.98; P=0.037), and in 90 (2.13%) versus 69 (1.62%) patients with SCAD (RR, 1.32; 95% CI, 0.97-1.81; P=0.081; P-interaction=0.007). Conclusions While there was no evidence for differences in efficacy between treatment strategies by subgroup, the experimental strategy appeared to reduce bleeding risk in patients with ACS but not in patients with SCAD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Impaired Touchscreen Skills in Parkinson's Disease and Effects of Medication.

BACKGROUND: Deficits in fine motor skills may impair device manipulation including touchscreens in people with Parkinson's disease (PD). OBJECTIVES: To investigate the impact of PD and anti-parkinsonian medication on the ability to use touchscreens. METHODS: Twelve PD patients (H&Y II-III), OFF and ON medication, and 12 healthy controls (HC) performed tapping, single and multi-direction sliding tasks on a touchscreen and a mobile phone task (MPT). Task performance was compared between patients (PD-OFF, PD-ON) and HC and between medication conditions. RESULTS: Significant differences were found in touchscreen timing parameters, while accuracy was comparable between groups. PD-OFF needed more time than HC to perform single (P = 0.048) and multi-direction (P = 0.004) sliding tasks and to grab the dot before sliding (i.e., transition times) (P = 0.040; P = 0.004). For tapping, dopaminergic medication significantly increased performance times (P = 0.046) to comparable levels as those of HC. However, for the more complex multi-direction sliding, movement times remained slower in PD than HC irrespective of medication intake (P < 0.050 during ON and OFF). The transition times for the multi-direction sliding task was also higher in PD-ON than HC (P = 0.048). Touchscreen parameters significantly correlated with MPT performance, supporting the ecological validity of the touchscreen tool. CONCLUSIONS: PD patients show motor problems when manipulating touchscreens, even when optimally medicated. This hinders using mobile technology in daily life and has implications for developing adequate E-health applications for this group. Future work needs to establish whether touchscreen training is effective in PD.

Durable Physiological Changes and Decreased Syncope Burden 12 Months After Unifocal Right-Sided Ablation Under Computed Tomographic Guidance in Patients With Neurally Mediated Syncope or Functional Sinus Node Dysfunction.

[Figure: see text].