Optimising Percutaneous Coronary Interventions: The Impact of Stent Type and Diameter on Long-Term Clinical Outcomes in Large Coronary Arteries.

Background and Objectives: Our study aimed to reveal the effect of using 4 mm bare-metal stents (BMS), 4 mm drug-eluting stents (DES), or 3 mm DES with 4 mm diameter balloon post-dilation strategies on long-term clinical outcomes and endpoints for large-diameter coronary artery percutaneous coronary intervention (PCI). Materials and Methods: In our study, patients who had undergone PCI were retrospectively screened between January 2014 and July 2020. The study included 350 patients and was divided into three groups; Group I (n = 134) included patients with direct 4.0 mm BMS implantation, Group II (n = 109) included patients with direct 4.0 DES implantation, and Group III (n = 107) included patients with 4mm NC post-dilatation after 3 mm DES implantation. Primary endpoints were determined as target lesion revascularisation, cardiac mortality, and myocardial infarction associated with the target vessel. Our secondary endpoint was all-cause mortality. Results: No differences were observed between the groups in terms of the baseline variables. Stent length was the highest in Group II and the shortest in Group III. There were no significant differences between the groups regarding major adverse cardiovascular events (MACE). Conclusions: Our study suggests that in percutaneous coronary interventions for non-complex lesions, there is no significant difference in MACE outcomes when directly implanting a 4 mm diameter DES, a 4 mm diameter BMS, or a 3 mm diameter DES, followed by post-dilation with an appropriately sized NC balloon when the target vessel diameter is in the range of 4 to 4.4 mm.

Evaluation of Atrial Electromechanical Delay and Left Atrial Phasic Function in Individuals with Electrocardiographic Early Repolarization Pattern.

Background: Atrial electromechanical delay (EMD) and left atrial (LA) phasic function have been demonstrated to be predictors for the development of atrial fibrillation (AF). In the present study, we aimed to evaluate atrial EMD and LA phasic function in individuals with electrocardiographic early repolarization pattern (ERP). Methods: Eighty consecutive individuals with ERP and 40 age- and gender-matched control subjects without ERP were compared in this cross-sectional study. Atrial electromechanical coupling (Pa') was measured from lateral mitral annulus (Pa'lateral), septal mitral annulus (Pa'septal), and lateral tricuspid annulus (Pa'tricuspid) using tissue Doppler echocardiography to calculate intra- and inter-atrial EMD. LA maximal volume, LA minimal volume, and LA volume before atrial contraction were calculated using the biplane area-length method to assess LA phasic function. Results: LA diameter, LA volume index, Pa'lateral, Pa'septal, Pa'tricuspid electrical activity and intra-left atrial EMD were significantly increased in the ERP patients. Mitral lateral, septal, tricuspid lateral annular tissue Doppler s' and e' waves were significantly decreased in the ERP patients. There were no significant difference between the groups in terms of interatrial EMD, intra-right atrial EMD, LA total emptying volume and LA total emptying fraction indicating LA reservoir function, LA passive emptying volume and LA passive emptying fraction indicating LA conduit function, LA active emptying volume and LA active emptying fraction indicating LA pump function. Conclusions: Left atrial EMD parameters are affected in individuals with ERP, but LA phasic functions are not affected. Further prospective studies are needed to clarify whether individuals with ERP have an increased susceptibility to AF.

Effects of hydrodissection on anesthesia characteristics in ultrasound guided infraclavicular brachial plexus blockade.

BACKGROUND: The development of ultrasonography technology and its widespread application have increased peripheral nerve block applications, especially in limb surgeries, since it reduces complication rates and increases success rates in peripheral nerve block applications. However, even experienced physicians need to direct a large number of needles and injections for adequate local anesthetic spread, which can cause accidental vascular puncture and local anesthetic systemic toxicity. Such complications can be prevented by hydrodissection and a safer and successful anesthesia can be provided to patients in this study, it was aimed to investigate the effects of hydrodissection on anesthesia characteristics in the infraclavicular brachial plexus blockade. MATERIALS AND METHODS: Ninety patients were included in our study after approval by the Ethics Committee. These patients were randomly divided into 2 groups (Group I: Infraclavicular brachial plexus blockade with normal method and Group II: infraclavicular brachial plexus blockade with hydrodissection). After obtaining patient consent, monitoring and vascular access were provided. Group I patients were mixed with 30 mL of local anesthetic mixture (15 mL of distilled water and 15 mL of 0.5% bupivacaine), and Group II patients were treated with 15 mL of distilled water by hydrodissection and 15 mL of 0.5% bupivacaine anesthesia resident. Block characteristics were evaluated and recorded every 5 minutes for the first 30 minutes by a blinded observer. The sensory block score was 7, the total score was 14 or above, and the block was considered successful, and the patient was ready for surgery. Postoperative block removal times, analgesia, and complications were evaluated and recorded. RESULTS: A significant difference was found between the sensory and motor block onset times and postoperative VAS scores between the normal and hydrodissection groups (P < .05). There were no significant differences in terms of block application times, postoperative block removal times, and complications between the groups. CONCLUSION: In this study, it has been shown that hydrodissection in peripheral nerve blocks does not lag in terms of block success and characteristics compared to normal methods, whereas anesthetists with less experience in peripheral nerve block experience obtain safer and more successful results in practice.

Low-Dose Slow Infusion Tissue Plasminogen Activator (tPA) in Treatment of Thrombotic Coronary Artery Occlusions: Case Series and Literature Review.

Thrombotic coronary artery occlusions usually manifest as acute coronary syndrome with cardiogenic shock, acute pulmonary edema, cardiac arrest, fatal arrhythmias, or sudden cardiac death. Although it usually occurs based on atherosclerosis, it can also occur without atherosclerosis. There is no predictor of coronary artery thrombosis clinically and no consensus regarding the optimal treatment. In the current literature, treatment options include emergency coronary artery bypass grafting, entrapment of thrombus in vessel wall with stent implantation, intracoronary thrombolysis, glycoprotein IIb/IIIa inhibitors, anticoagulation with heparin, and thrombus aspiration as reperfusion strategies. Here, we reviewed a new treatment strategy based on the literature, and a case series with successful results in hemodynamically stable patients with low-dose slow infusion tissue plasminogen activator (tPA) for thrombotic coronary artery occlusions that allow coronary flow was reported. Prospective randomized studies and common consensus are needed on low-dose, slow-infusion tissue plasminogen activator treatment regimen and optimal treatment management for thrombotic coronary artery occlusions.

Comparison of left atrial deformation parameters between renal transplant and hemodialysis patients.

BACKGROUND: Renal transplantation (RT) has been demonstrated to improve left ventricular systolic function. However, only few studies have attempted to reveal the effects of transplantation on left atrial (LA) function. In our study, we aimed to compare LA function between RT and hemodialysis patients. METHODS: This cross-sectional study included 75 consecutive patients with RT, and 75 age- and gender-matched patients on maintenance hemodialysis. LA strain and strain rate (SR) analyzed by two-dimensional (2D) speckle tracking echocardiography (STE) were compared between the groups in addition to standard echocardiographic parameters. RESULTS: LA strain during reservoir phase (29.88 ± 5.76% vs 26.11 ± 5.74%, P < .001), LA strain during conduit phase (- 15.28 ± 5.00% vs - 12.92 ± 4.38%, P = .003), and LA strain during contraction phase (- 14.60 ± 3.32% vs - 13.19 ± 3.95%, P = .020) were higher in the transplantation group. Similarly, LA peak SR during reservoir phase (1.54 ± 0.33 s- 1 vs 1.32 ± 0.33 s- 1, P < .001), LA peak SR during conduit phase (- 1.47 ± 0.49 s- 1 vs - 1.12 ± 0.42 s- 1, P < .001), and LA peak SR during contraction phase (- 2.13 ± 0.46 s- 1 vs - 1.83 ± 0.58 s- 1, P = .001) were higher in the transplantation group as well. CONCLUSIONS: LA function assessed by 2D STE was better in RT patients than hemodialysis patients. This may suggest favorable effects of RT on LA function.

Baseline Anemia Is an Independent Predictor of Long-Term Mortality in Patients Undergoing Transcatheter Aortic Valve Implantation.

This study aimed to investigate the relationship between baseline anemia and long-term mortality in a single-center retrospective study involving patients undergoing transcatheter aortic valve implantation (TAVI). The study population included 412 consecutive patients undergoing TAVI at a center for severe aortic valve stenosis between August 2011 and November 2018. The primary end point of the study was all-cause mortality. Baseline anemia was present in 50% of our study cohort. During the median follow-up of 29 months, all-cause mortality was observed in 40.3% of the whole study population and was more frequently observed in the anemic group compared with the nonanemic group (53.5% vs 27.1%, P < .001, respectively). Cox-regression analysis revealed that Society of Thoracic Surgeons Predicted Risk of Mortality score, previous stroke, pericardial tamponade, and neutrophil-lymphocyte ratio count are independent predictors of long-term mortality after TAVI. Additionally, the presence of anemia at baseline was an independent predictor of long-term mortality with a 2.3-fold difference in the anemic group compared with the nonanemic group (hazard ratio: 2.31, 95% CI: 1.59-3.37, P < .001). Baseline anemia was observed in half of our patient population undergoing TAVI, and baseline anemia was found to be an independent predictor of long-term mortality after TAVI.

Effect of ranolazine on Tp-e interval, Tp-e/QTc, and P-wave dispersion in patients with stable coronary artery disease.

INTRODUCTION: Ranolazine is an antianginal drug and also exhibits antiarrhythmic effect by affecting action potential time, refractory period, and repolarization reserve. We evaluated the effect of ranolazine therapy on myocardial repolarization parameters (Tp-e, QT, QTc intervals, Tp-e/QT, and Tp-e/QTc ratios), index of cardiac electrophysiological balance (iCEB) (QT/QRS, QTc/QRS) and P-wave dispersion (PWD) in patients with stable coronary artery disease (CAD). METHODS: This study included 175 patients, aged between 35 and 90 years who were followed with stable CAD for at least 3 months. Ninety patients had been receiving ranolazine for at least 1 month, and 85 patients had never received ranolazine. All patients' basic demographic data, risk factors, medications, and echocardiographic parameters recorded. Myocardial repolarization parameters, P-wave times, and PWD were analyzed from 12 lead electrodes. RESULTS: There was no variation between the groups in terms of basic demographic parameters and CAD risk factors. Tp-e interval (87.3 ± 14.4 vs. 90.8 ± 12.4 msn, P < .001), Tp-e/QT (0.22 ± 0.04 vs. 0.23 ± 0.03; P = .03), Tp-e/QTc (0.21 ± 0.04 vs. 0.22 ± 0.04 P = .001), and PWD (39.2 ± 13.7 vs. 43.5 ± 12.9 P = .028) were significantly lower in the ranolazine group. But iCEB was similar in both groups. In multivariate analysis after adjusted confounding factors such as age and BMI, Tp-e/QTc ratio, QTc, Pmax, and PWD were found significantly in ranolazine group again. CONCLUSION: Tp-e/QTc ratio, QTc, Pmax, and PWD were significantly lower in stable CAD patients under ranolazine therapy. In stable CAD patients, the prognostic significance of ranolazine for arrhythmic events requires further evaluation of these parameters through long-term follow-up and large-scale prospective studies.

Assessment of Arterial Stiffness with Cardio-Ankle Vascular Index in Patients with Mitral Annular Calcification.

OBJECTIVE: Arterial stiffness is related to arteriolosclerotic diseases and is a marker of adverse cardiovascular events. Mitral annular calcification (MAC) is progressive calcium deposition on the posterior and inferior mitral annulus and is associated with atherosclerotic cardiovascular diseases. Cardio-ankle vascular index (CAVI) is a measurement technique used to estimate the degree of arterial stiffness without effect from blood pressure. The aim of this study is to research arterial stiffness using CAVI in patients with MAC. MATERIALS AND METHODS: The study was cross-sectional and observational and included 98 patients with MAC confirmed by echocardiography who referred to the cardiology clinics and met study inclusion criteria and 38 controls without MAC. CAVI measurements were obtained by using the Vascular Screening System VaSera VS-1000 (Fukuda Denshi, Tokyo, Japan) device. RESULTS: The two groups were similar in terms of demographic characteristics, including age, sex, hypertension, coronary artery disease, body surface area, and smoking (P > .05). Left atrial volume index was significantly higher in patients with MAC compared with the control group (P < .001). Right arm CAVI, left arm CAVI, and mean CAVI were significantly higher in the MAC group than the control group (P = .037, P = .005, and P = .014, respectively) and increased with MAC severity. There was a significant positive correlation between mean CAVI and MAC grade (r = 0.278, P = .001). Also, when ankle-brachial index (ABI) was measured with CAVI, left and right extremity ABI values were significantly lower in patients with MAC (P = .017 and P = .005, respectively). CONCLUSION: CAVI increased in all patients with MAC and associated with increasing grade of calcification.

Effect of supraphysiological estrogen levels on arterial stiffness and hemodynamic parameters.

OBJECTIVE: The present study evaluates the arterial stiffness and hemodynamic parameters in patients with a supraphysiological estrogen level due to in vitro fertilization (IVF) with controlled ovarian hyperstimulation (COH). METHODS: A total of 82 female patients aged 24-45 years were included. Their arterial stiffness parameters were analyzed before and after the appropriate COH protocol involving arteriography using Mobil-O-Graph NG (IEM GmbH, Stolberg, Germany) 24-hour ambulatory blood pressure monitor. RESULTS: Systolic, diastolic, mean, central systolic, and diastolic blood pressures, as well as peripheral vascular resistance, were significantly lower after COH therapy (p=0.001, 0.002, <0.001, <0.001, 0.040, and <0.001, respectively). In contrast, there was no statistically significant difference observed in heart rate, pulse pressure, or cardiac output. The pulse wave velocity measurement was significantly lower after COH than the baseline levels [5.3 m/s (4.5-6.9 m/s) versus 5.4 m/s (4.7-7.3 m/s,); p<0.001], but the augmentation index was not significantly different [28% (4%-41%) versus 29% (5%-43%); p=0.090]. When the patients were grouped according to the occurrence of a pregnancy after IVF therapy, all parameters were not different between the pregnancy (+) and pregnancy (-) patients (p>0.05). CONCLUSION: Arterial stiffness and hemodynamic parameters significantly decreased in IVF patients who underwent COH therapy. The long-term clinical significance of this short-term effect should be investigated with prospective studies. There was no significant difference in all parameters before and after COH when the pregnancy (+) and pregnancy (-) patients were compared.

Effect of dialysis and transplantation on myocardial repolarization parameters and P-wave dispersion in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) patients are at higher risk for cardiac arrhythmias. The risk of arrhythmia may change with different treatment modalities. We proposed to compare the effects of varied therapy methods on myocardial repolarization parameters (Tp-e, QT, QTc intervals, Tp-e/QT, Tp-e/QTc ratios) and P-wave dispersion (PWD) in patients with CKD. METHODS: Three groups were formed from the patients aged between 18 and 65 years, as Group 1 consisting of CKD patients receiving hemodialysis (HD) three times a week, Group 2 consisting of predialysis CKD patients and Group 3 consisting of CKD patients who underwent successful transplantation. All patients' basic demographic data, risk factors, and echocardiographic parameters were recorded, and electrocardiographic repolarization parameters and PWD were analyzed. RESULTS: The PR, QT, and QTc intervals were significantly shorter in the transplantation group compared to the other groups (P = .020, P < .001, P = .035; respectively). Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly higher in the predialysis group compared to the other groups (P < .001, P < .001, P = .001; respectively), while there was no significant variation between the HD and transplantation groups (P > .05). PWD was significantly increased in the predialysis group compared to other two groups (P < .001), while no significant variation between the HD and transplantation groups was observed. CONCLUSION: We found that the Tp-e interval, Tp-e/QT, Tp-e/QTc, and PWD were significantly higher in the predialysis CKD group, but the PR, QT, and QTc intervals were significantly shorter in the transplantation group compared to the other groups. The prognostic significance and prediction of these parameters in arrhythmic events in CKD patients requires further evaluation with long-time follow-up.

The relationship between calcific severe aortic stenosis and systemic immune-inflammation index.

AIM: Calcific aortic stenosis (AS) is a common valvular disease especially in elderly population. Inflammation plays significant role in the pathophysiological mechanism. Systemic immune-inflammation index (SII) is a novel marker of immune system and inflammation that includes neutrophil, lymphocyte, and platelet cell counts. The aim of this study was to investigate the predictive value of SII in calcific severe AS. MATERIALS AND METHODS: Severe calcific AS patients were categorized into two groups: High flow-high gradient (HFHG) AS (n = 289) and low flow-low gradient AS (n = 79). Control group included 273 patients with similar clinical and demographic characteristics but without AS. SII was calculated as absolute platelet count × absolute neutrophil count/absolute lymphocyte count. RESULTS: SII levels were 525 ± 188, 835 ± 402, and 784 ± 348 in control, HFHG AS, and LFLG AS groups, respectively (P < .001). Correlation analyses revealed significant and positive correlation between SII and mean aortic transvalvular pressure gradient (r = .342, P < .001), and negative and significant correlation between SII and AVA (r = -.461, P < .001). Multivariate analysis performed in separate models demonstrated sex, CAD, LDL, and SII levels (Odds ratio [OR]: 1.004, 95 CI%:1.003-1.004) as independent predictors of severe AS in Model 1. According to Model 2, sex, CAD, LDL, and high SII (>661) (OR:5.78, 95 CI%:3.93-4.89) remained as independent predictors of severe AS. CONCLUSION: SII levels can be useful to predict severe calcific AS patients and significantly correlate with AVA and mean aortic transvalvular pressure gradient.

Comparison Between the Effects of Bupivacaine and Levobupivacaine for Spinal Anesthesia on QT Dispersion.

BACKGROUND: Bupivacaine and Levobupivacaine are frequently used local anesthetic drugs in spinal anesthesia practice. Both agents have arrhythmic effects on the heart. However, there is no clear information about which agent is more arrhythmogenic. OBJECTIVE: The aim of this article is to investigate the effects of bupivacaine and its S (-)-enantiomer, levobupivacaine, on cardiac arrhythmias in patients. METHODS: The study included 40 patients scheduled for inguinal hernia surgery. Patients were randomly divided into the following two groups using a sealed envelope method: Group I, the bupivacaine group (n = 20); and Group II, the levobupivacaine group (n = 20). The QT values were taken preoperatively and during the 10th of the spinal block, the 10th of the surgical incision, and the 10th postoperative minute. Additionally, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), oxygen saturation (SO2), and heart rate (HR) values, in addition to motor block (Bromage scale) levels and durations, were recorded for each patient. RESULTS: HR values measured at 10 min after spinal block were significantly higher than the baseline values in the levobupivacaine group (p < 0.05). The corrected QT interval (QTc) values increased significantly at 10 minutes after spinal block and at 10 min postoperatively in the bupivacaine group (p < 0.05). QTd and QTcd measurements were taken at the 10th minute of spinal anesthesia, the 10th minute of the incision, and the 10th minute postoperatively. When compared to the levobupivacaine group, a statistically significant increase was found in the bupivacaine group (p < 0.05). CONCLUSION: Levobupivacaine allows greater hemodynamic stability, while bupivacaine affects QTc and QTd measurement times more. As such, we believe that levobupivacaine may be a better alternative to bupivacaine during clinical practice, particularly in patients with cardiac problems.

Resuscitated sudden cardiac death due to severe hypokalemia caused by teff grain herbal tea: A case report.

Obesity is a common health problem and the prevalence is increasing worldwide. The improper and unregulated use of unconventional therapies, especially herbal treatment methods, has grown due to widespread availability. In our case, a 41-year-old male patient developed palpitation, confusion, loss of consciousness, and cardiac arrest while at home. An emergency medical team was called and chest compressions were performed by his wife until the medical team arrived. Ventricular fibrillation was detected on the monitor 5 minutes after the cardiac arrest occurred and the patient was defibrillated. A physical evaluation revealed hypotension and tachycardia. Electrocardiography (ECG) showed a fast idioventricular rhythm with capture and fusion beats and evident J waves in leads DII, DIII, and aVF. Brain magnetic resonance imaging and thoracic tomography revealed no pathology to explain his clinical condition and the coronary angiography results were not significant. The laboratory parameters included potassium (K): 2.23 mEq/L, ionized K (arterial blood): 2.43 mEq/L, sodium: 142 mEq/L, calcium: 9.3 mg/dL, creatinine: 1.6 mg/dL, pH: 7.29, cardiac troponin I: 0.12 (normal range: 0-0.11 ng/mL) and creatinine kinase mass: 8.3 (normal range: 0-3.23 ng/mL). After fluids and electrolyte replacement therapy were administered, the ECG results revealed narrow QRS complex atrial fibrillation followed by a normal sinus rhythm with a 490 ms corrected QT interval. The patient was extubated in follow-up. There were no risk factors for coronary artery disease, no history of drug or other substance use, and no exposure to excessive emotional or physical stress. The patient said that he had been consuming a large quantity of teff tea for 5 days to lose weight. He was discharged without any complications and has been asymptomatic in 9 months of follow-up. The inappropriate use of weight loss alternatives, especially herbal therapies such as teff tea, and the incidence of associated side effects are increasing due to wide availability and easy access. The general population should be warned about this issue.

Comparison of General Anesthesia (Sevoflurane) and Spinal Anesthesia (Levobupivacaine) Methods on QT Dispersion in Inguinal Hernia Operations.

Introduction Arrhythmias are one of the most frequently seen issues during surgical operations. In this study, we investigated and compared the effects on the QT dispersion of patients when using a method of volatile inhalation mask anesthesia with sevoflurane (VIMA: Group I) and when spinal anesthesia was performed with levobupivacaine (Group II). Methods The study included 40 patients who had American Society of Anesthesiology scores of I-II (ASA I-II), were aged from 18 to 65 years, and were scheduled for inguinal hernia operations. Approval of the university ethics committee was obtained before the study began. All patients had measurements taken for non-invasive blood pressure, including systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SO2) values. The QT intervals were measured using the 12-derivation electrocardiogram (ECG) device (Cardiofax V). Our study was performed with randomization using the closed envelope method. Results When the percentage differences of the HR values from the initial period in both groups were compared, we observed significant differences between the groups, with increases in the VIMA group at the second period as well as increases in the VIMA group at the fourth, fifth, sixth, seventh, and ninth periods but decreases in the spinal anesthesia group for these periods. There were statistically significant differences between the two groups at the third and fifth periods when the percentage differences of the QTc values from the initial period were compared. We observed increases in the spinal anesthesia group. Conclusion In our study, we suggest that the tendency toward arrhythmia may be reduced by choosing general anesthesia with sevoflurane rather than levobupivacaine in patients with cardiac complaints who are undergoing regional anesthesia and/or taking medication that affects QT intervals.

The effect of cardiac resynchronization therapy on arterial stiffness and central hemodynamic parameters.

INTRODUCTION: Cardiac resynchronization therapy (CRT) is a device-based method of treatment which decreases morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). This study was aimed to investigate the effects of CRT on hemodynamic and arterial stiffness parameters evaluated by noninvasive method, and determine whether there is a correlation between the changes after CRT in these parameters and the clinical response to CRT or not. METHODS: The study included 46 patients with HFrEF who were planned to undergo CRT implantation. Before the CRT implantation, clinical and demographic data were recorded from all patients. Hemodynamic and arterial stiffness parameters were measured oscillometrically by an arteriograph before CRT implantation. The patients were re-evaluated minimum three months after CRT; the above-mentioned parameters were measured again and compared to the pre-CRT period. RESULTS: Compared to the period before CRT, mean systolic blood pressure (SBP) (116.8 ± 19.1 mm Hg vs 127.7 ± 20.9 mm Hg, P = .005), central SBP (cSBP) (106.2 ± 17.3 mm Hg vs 116.8 ± 18.7 mm Hg, P = .015), cardiac output (CO) (4.6 ± 0.8 lt/min vs 5.1 ± 0.8 lt/min, P = .002), stroke volume (65.6 ± 16.3 mL vs 72.0 ± 14.9 mL), and pulse wave velocity (PWV) (10 ± 1.6 m/sec vs 10.4 ± 1.8 m/sec, P = .004) increased significantly in post-CRT period. In addition, the same parameters were significantly increased post-CRT period in patients with clinical response. However, there was not any similar increase in nonresponder patients. CONCLUSION: This study demonstrated that SBP, CO, and PWV increased significantly after CRT. The modest increases in these parameters were observed to be associated with positive clinical outcomes.