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OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of oxidized regenerated cellulose (ORC) in patients who underwent coronary artery bypass grafting (CABG) surgery and to compare the results of patients in whom ORC was used or not used for control of bleeding. METHOD: Pre-, intra-, and post-operative demographic and medical parameters of the patients in whom ORC was used or not used were compared. Quantitative data were analyzed with mean and standard deviation. Group differences were assessed with the Mann-Whitney U test. RESULTS: It was found that the duration of surgery, average numbers of erythrocyte and fresh frozen plasma (FFP) transfusions during surgery, average post-operative FFP transfusion count, duration of intensive care unit stay, and chest tube removal times were lower in the ORC group compared to the control group, and all these differences were statistically significant (p < 0.05 for all of these parameters). CONCLUSIONS: The study successfully demonstrated the effective and safe use of topical ORC in controlling bleeding and preventing oozing during CABG surgeries.

OBJETIVO: Evaluar la eficacia y la seguridad de la celulosa regenerada oxidada (CRO) en pacientes sometidos a cirugía de injerto de derivación de arteria coronaria y comparar los resultados de los pacientes en los que se utilizó o no la CRO para el control del sangrado. MÉTODO: Se compararon los parámetros demográficos y médicos pre-, intra- y posoperatorios de los pacientes en los que se utilizó o no CRO. Los datos cuantitativos se analizaron con media y desviación estándar. Las diferencias grupales se evaluaron con la prueba U de Mann Whitney. RESULTADOS: Se encontró que la duración de la cirugía, el número promedio de transfusiones de eritrocitos y de plasma fresco congelado durante la cirugía, el recuento promedio de transfusiones de plasma fresco congelado posoperatorias, la duración de la estadía en la unidad de cuidados intensivos y los tiempos hasta la extracción del tubo torácico fueron menores en el grupo de CRO en comparación con el grupo control, y todas estas diferencias fueron estadísticamente significativas (p < 0.05). CONCLUSIONES: El estudio demostró con éxito el uso eficaz y seguro de la CRO tópica para controlar el sangrado y prevenir la supuración durante las cirugías de derivación de arteria coronaria.

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INTRODUCTION: The effect of pump flow type on perfusion in coronary surgery using cardiopulmonary bypass (CPB) is discussed. We aimed to evaluate the effect of pump flow type on cognitive functions with neurocognitive function tests. METHODS: One hundred patients who underwent isolated coronary artery bypass surgery between November 2020 and July 2021 were divided into two equa groups. Groups were formed according to pump flow type pulsatile (Group 1) and non-pulsatile (Group 2). Clock drawing test (CDT) and standardized mini mental test (SMMT) were performed on the patients in both groups in the preoperative period, on the 1st preoperative day, and on the day before discharge. Neurocognitive effects were compared with all follow-up parameters. RESULTS: There was no difference between the groups in terms of demographic data and in terms of neurocognitive tests performed before the operation. SMMT on postoperative day 1 (Group I: 27.64 ± 1.05; Group II: 24.44 ± 1.64; P=0.001) and CDT (Group I: 5.4 ± 0.54; Group II: 4 .66 ± 0.52; P=0.001), and SMMT on the day before discharge (Group I: 27.92 ± 1.16; Group II: 24.66 ± 1.22; P=0.001) and CDT (Group I: 5 It was calculated as .66 ± 0.48; Group II: 5.44 ± 0.5; P=0.001). The duration of intensive care and hospitalization were higher in the non-pulsatile group. CONCLUSION: We think that the type of pump flow used in coronary artery bypass surgery using CPB is effective in terms of neurocognitive functions and that pulsatile flow makes positive contributions to this issue.

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INTRODUCTION: The aim of this study was to identify perioperative risk factors of laryngeal symptoms and to develop an implementable risk prediction model for Chinese hospitalized patients undergoing coronary artery bypass grafting (CABG). METHODS: A total of 1476 Chinese CABG patients admitted to Wuhan Asian Heart Hospital from January 2020 to June 2022 were included and then divided into a modeling cohort and a verification cohort. Univariate analysis was used to identify laryngeal symptoms risk factors, and multivariate logistic regression was applied to construct a prediction model for laryngeal symptoms after CABG. Discrimination and calibration of this model were validated based on the area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow (H-L) test, respectively. RESULTS: The incidence of laryngeal symptoms in patients who underwent CABG was 6.48%. Four independent risk factors were included in the model, and the established aryngeal complications risk calculation formula was Logit (P) = -4.525 + 0.824 × female + 2.09 × body mass index < 18.5 Kg/m2 + 0.793 × transesophageal echocardiogram + 1.218 × intensive care unit intubation time. For laryngeal symptoms, the area under the ROC curve was 0.769 in the derivation cohort (95% confidence interval [CI]: 0.698-0.840) and 0.811 in the validation cohort (95% CI: 0.742-0.879). According to the H-L test, the P-values in the modeling group and the verification group were 0.659 and 0.838, respectively. CONCLUSION: The prediction model developed in this study can be used to identify high-risk patients for laryngealsymptoms undergoing CABG, and help clinicians implement the follow-up treatment.

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Background: Ischemic heart disease (IHD) is a major global health issue and a leading cause of death. This study compares the effectiveness of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in the management of IHD, focusing on their impact on revascularization, myocardial infarction (MI), and post-procedural stroke. This study aimed to evaluate and compare the effectiveness of PCI and CABG in treating IHD based on an exhaustive literature review of the past 5 years, emphasizing recent advancements and outcomes in IHD management. Methods: A comprehensive literature review analyzed 32 randomized controlled trials (RCTs) retrieved from databases such as PubMed, Cochrane Library, and Google Scholar. The study specifically assessed the incidences of revascularization, stroke, and MI in patients treated with either PCI or CABG. The comparison between CABG and PCI exclusively focused on lesions with a SYNTAX score exceeding 32. Results: Our findings highlight CABG's significant efficacy over PCI in reducing revascularization and MI. The aggregated Mantel-Haenszel (M-H) value for revascularization was 1.85 (95% confidence interval (CI): 1.65 - 2.07), signifying CABG's advantage. Additionally, CABG demonstrated superior performance in diminishing MI occurrences (M-H = 2.71, 95% CI: 1.13 - 6.53). In contrast, PCI was more effective in reducing stroke (M-H = 0.80, 95% CI: 0.60 - 1.10). Conclusion: The study confirms CABG's superiority in reducing revascularization and MI in IHD patients, highlighting PCI's effectiveness in reducing stroke risk. These findings underscore the importance of personalized treatment strategies in IHD management and emphasize the need for ongoing research and evidence-based guidelines to aid in treatment selection for IHD patients.

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INTRODUCTION: Minimally invasive coronary artery bypass grafting (MICS CABG) offers a new paradigm in coronary revascularization. This study aims to compare the outcomes of MICS CABG with those of conventional median sternotomy CABG (MS CABG) within a growing minimally invasive cardiac surgical program in Singapore. METHODS: Propensity matching produced 111 patient pairs who underwent MICS CABG or MS CABG between January 2009 and February 2020 at the National University Heart Centre, Singapore. Minimally invasive direct coronary artery bypass surgery patients were matched to single- or double-graft MS CABG patients (Group 1). Multivessel MICS CABG patients were matched to MS CABG patients with equal number of grafts (Group 2). RESULTS: Overall, MICS CABG patients experienced shorter postoperative length of stay (P<0.071). In Group 2, procedural duration (P<0.001) was longer among MICS CABG patients, but it did not translate to adverse postoperative events. Postoperative outcomes, including 30-day mortality, reopening for bleeding, new onset atrial fibrillation as well as neurological, pulmonary, renal, and infectious complications were comparable between MICS and MS CABG groups. CONCLUSION: MICS CABG is a safe and effective approach for surgical revascularization of coronary artery disease and trends toward a reduction in hospital stay.

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INTRODUCTION: In this study, we aimed to evaluate the most common causes of recurrent angina after coronary artery bypass grafting (CABG) and our treatment approaches applied in these patients. METHODS: We included all patients who underwent CABG, with or without percutaneous coronary intervention after CABG, at our hospital from September 2013 to December 2019. Patients were divided into two groups according to the time of onset of anginal pain after CABG. Forty-five patients (58.16 ± 8.78 years) had recurrent angina in the first postoperative year after CABG and were specified as group I (early recurrence). Group II (late recurrence) comprised 82 patients (58.05 ± 8.95 years) with angina after the first year of CABG. RESULTS: The mean preoperative left ventricular ejection fraction was 53.22 ± 8.87% in group I, and 54.7 ± 8.58% in group II (P=0.38). No significant difference was registered between groups I and II regarding preoperative angiographic findings (P>0.05). Failed grafts were found in 27.7% (n=28/101) of the grafts in group I as compared to 26.8% (n=51/190) in group II (P>0.05). Twenty-four (53.3%) patients were treated medically in group I, compared with 54 (65.8%) patients in group II (P=0.098). There was a need for intervention in 46.6% (n=21) of group I patients, and in 34.1% (n=28) of group II patients. CONCLUSION: Recurrent angina is a complaint that should not be neglected because most of the patients with recurrent angina are diagnosed with either native coronary or graft pathology in coronary angiography performed.

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INTRODUCTION: Atrial fibrillation is the main complication in the postoperative period of cardiovascular surgery. Its genesis is multifactorial, so its rapid identification to mitigate the associated risks is essential. OBJECTIVE: To evaluate the incidence of atrial fibrillation in patients undergoing coronary artery bypass grafting (CABG) and its relationship with other complications in our setting. METHODS: This is a multicenter, observational study involving patients undergoing isolated CABG between 2017 and 2019 with data from the Registro Paulista de Cirurgia Cardiovascular (or REPLICCAR II). Variables were prospectively collected in REDCap following the definitions given by version 2.73 of the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Data were collected with prior authorization from the local ethics committee and analyses performed in R software. RESULTS: A total of 3,803 patients were included, of these 605 had postoperative atrial fibrillation (POAF). In order to adjust the groups, propensity score matching was used. Such analyses resulted in 605 patients in each group (without POAF vs. with POAF). Among patients with POAF, the mean age was 67.56 years, with a prevalence of males (73.6%, 445 patients). Patients belonging to the group with POAF had a mortality rate of 9.26% (P=0.007), longer ventilation time (P<0.001), pneumonia (P<0.001), and sepsis (P<0.001). In multiple analysis, acute renal dysfunction (P=0.032) and longer intensive care unit stay (P<0,001) were associated with the presence of POAF. CONCLUSION: POAF in CABG is associated with longer intensive care unit and hospital stay, as well as renal dysfunction, pneumonia, and in-hospital mortality.

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INTRODUCTION: It is not yet clear whether cardiac surgery by mini-incision (minimally invasive cardiac surgery [MICS]) is overall less painful than the conventional approach by full sternotomy (FS). A meta-analysis is necessary to investigate polled results on this topic. METHODS: PubMed®/MEDLINE, Cochrane CENTRAL, Latin American and Caribbean Health Sciences Literature (or LILACS), and Scientific Electronic Library Online (or SciELO) were searched for all clinical trials, reported until 2022, comparing FS with MICS in coronary artery bypass grafting (CABG), mitral valve surgery (MVS), and aortic valve replacement (AVR), and postoperative pain outcome was analyzed. Main summary measures were the method of standardized mean differences (SMD) with a 95% confidence interval (CI) and P-values (considered statistically significant when < 0.05). RESULTS: In AVR, the general estimate of postoperative pain effect favored MICS (SMD 0.87 [95% CI 0.04 to 1.71], P=0.04). However, in the sensitivity analysis, there was no difference between the groups (SMD 0.70 [95% CI -0.69 to 2.09], P=0.32). For MVS, it was not possible to perform a meta-analysis with the included studies, because they had different methodologies. In CABG, the general estimate of the effect of postoperative pain did not favor any of the approaches (SMD -0.40 [95% CI -1.07 to 0.26], P=0.23), which was confirmed by sensitivity analysis (SMD -0.02 [95% CI -0.71 to 0.67], P=0.95). CONCLUSION: MICS was not globally less painful than the FS approach. It seems that postoperative pain is more related to the degree of tissue retraction than to the size of the incision.

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INTRODUCTION: This study aimed to investigate the predictive value of the vasoactive-inotropic score (VIS) at different time points for postoperative prolonged mechanical ventilation (PMV) in adult congenital heart disease patients undergoing surgical treatment combined with coronary artery bypass grafting. METHODS: Patients were divided into two groups that developed PMV or not. The propensity score matching method was applied to reduce the effects of confounding factors between the two groups. VIS at different time points (VIS at the end of surgery, VIS6h, VIS12h, and VIS12h max) after surgery were recorded and calculated. The value of VIS in predicting PMV was analyzed by the receiver operating characteristic (ROC) curve, and multivariate logistic regression was used to analyze independent risk factors. RESULTS: Among 250 patients, 52 were in the PMV group, and 198 were in the non-PMV group. PMV rate was 20.8%. After propensity score matching, 94 patients were matched in pairs. At each time point, the area under the ROC curve predicted by VIS for PMV was > 0.500, among which VIS at the end of surgery was the largest (0.805). The optimal cutoff point for VIS of 6.5 could predict PMV with 78.7% sensitivity and 72.3% specificity. VIS at the end of surgery was an independent risk factor for PMV (odds ratio=1.301, 95% confidence interval 1.091~1.551, P<0.01). CONCLUSION: VIS at the end of surgery is an independent predictor for PMV in patients with adult congenital heart disease surgical treatment combined with coronary artery bypass grafting.

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OBJECTIVE: To investigate the association between body mass index (BMI), obesity, clinical outcomes, and mortality following coronary artery bypass grafting (CABG) in Brazil using a large sample with one year of follow-up from the Brazilian Registry of Cardiovascular Surgeries in Adults (or BYPASS) Registry database. METHODS: A multicenter cohort-study enrolled 2,589 patients submitted to isolated CABG and divided them into normal weight (BMI 20.0-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obesity (BMI > 30.0 kg/m2) groups. Inpatient postoperative outcomes included the most frequently described complications and events. Collected post-discharge outcomes included rehospitalization and mortality rates within 30 days, six months, and one year of follow-up. RESULTS: Sternal wound infections (SWI) rate was higher in obese compared to normal-weight patients (relative risk [RR]=5.89, 95% confidence interval [CI]=2.37-17.82; P=0.001). Rehospitalization rates in six months after discharge were higher in obesity and overweight groups than in normal weight group (χ=6.03, P=0.049); obese patients presented a 2.2-fold increase in the risk for rehospitalization within six months compared to normal-weight patients (RR=2.16, 95% CI=1.17-4.09; P=0.045). Postoperative complications and mortality rates did not differ among groups during time periods. CONCLUSION: Obesity increased the risk for SWI, leading to higher rehospitalization rates and need for surgical interventions within six months following CABG. Age, female sex, and diabetes were associated with a higher risk of mortality. The obesity paradox remains controversial since BMI may not be sufficient to assess postoperative risk in light of more complex and dynamic evaluations of body composition and physical fitness.

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OBJECTIVES: Coronary artery disease (CAD) and abdominal aortic aneurysm (AAA) are common arterial pathologies that might occur simultaneously; however, there is not enough evidence about the optimal strategy for patients with concomitant indications of coronary artery bypass grafting (CABG) and open repair of the AAA (AAOR). This study aims to present the outcomes in low and moderate cardiac surgical risk patients who underwent one-stage or two-stage elective CABG and AAOR in a middle-income country. METHODS: An observational, retrospective case series study was conducted. Patients who had low and moderate cardiac surgical risk (less than 8% mortality risk on the STS score) and had the concomitant indication for CABG and AAOR between December 2005 and August 2021 were included. Patients were assigned to one of three strategies: Group 1 underwent one-stage surgery for CABG and AAOR, Group 2 underwent two-stage surgery within the same in-patient stay, and Group 3 underwent two-stage surgery in a new in-patient stay within 6 months. RESULTS: Twenty seven, patients with simultaneous requirements of CABG and AAOR were identified, with a mean age of 69.5 ± 6.1 years and 92.6% were male. The most common comorbidities were hypertension at 77.8% and dyslipidemia at 55.6%. The average mortality risk calculated by the STS score was 2.09% ± 1.53%. In Group 1 (n = 9), 1/9 had in-hospital mortality and no reinterventions were needed. In Group 2 (n = 10), 1/10 had in-hospital mortality, and the most common postoperative complication was acute kidney injury 2/10. Furthermore, 2/10 required a reintervention. In Group 3 (n = 8), no in-hospital mortality was present, however, complications such as sepsis, atrial fibrillation, and acute kidney injury occurred in 2/8 patients each, and 2/8 required a reintervention. CONCLUSION: Patients with CAD and AAA that need a concomitant surgical correction with CABG and an AAOR are uncommon in contemporary practice, given the advances in endovascular therapy. When indicated, one-stage surgery can be performed in patients with low cardiac surgical risk, proper patient selection plays a fundamental role and might be performed in experienced centers. However, two-staged surgeries at the same or different inpatient stay may be considered for asymptomatic AAA with close monitoring during the postoperative period. These findings can hold significance for addressing sociodemographic barriers in low and middle-income countries. More robust and extensive studies are needed to make clear comparisons between the different strategies.

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INTRODUCTION: Although cardiopulmonary bypass procedures remain a critical treatment option for heart disease, they come with risks, including hemorrhage. Tranexamic acid is known to reduce morbidity and mortality in surgical hemorrhage. OBJECTIVE: This study aimed to evaluate the efficacy of tranexamic acid, which is routinely used to treat hemorrhage, in decreasing the amount of intraoperative and postoperative drainage. METHOD: A total of 80 patients who underwent cardiac surgery with cardiopulmonary bypass were included in this retrospective study. Forty patients who received tranexamic acid during the operation were assigned to Group 1, while 40 patients who did not receive tranexamic acid were assigned to Group 2. Patient data were collected from the hospital computer system and/or archive records after applying exclusion criteria, and the data were recorded. Statistical analyses were then performed to compare the data. RESULTS: Age, sex, height, weight, body surface area, flow, and ejection fraction percentages, preoperative hematological parameters, and intraoperative variables (except tranexamic acid) were similar between the groups (P>0.05). However, there were statistically significant differences between the groups in terms of intraoperative (through the heart-lung machine) and postoperative red blood cell transfusion rates, intraoperative and postoperative bleeding drainage amounts, as well as postoperative hematocrit, hemoglobin, platelet, and red blood cell levels (P<0.05). CONCLUSION: We concluded that intraoperative and postoperative use of tranexamic acid in patients who underwent coronary artery bypass grafting with cardiopulmonary bypass has positive effects on hematological parameters, reducing blood product use, and bleeding drainage amount.

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OBJECTIVE: This study aimed to determine the effects of inspiratory muscle training (IMT) on exercise capacity, respiratory muscle strength, length of hospital stay (LOS), and quality of life (QOL) following coronary artery bypass graft surgery. METHODS: The search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Handbook and included the databases MEDLINE, EMBASE, CINAHL, Scopus, and CENTRAL. The review included randomized controlled trials utilizing IMT during phase 1 or 2 postoperative cardiac rehabilitation (PoCR) versus alternative treatment (active or passive control) in patients following coronary artery bypass graft surgery. RESULTS: Fifteen studies were included (11 phase 1 studies, 4 phase 2 studies) with no reported adverse events. In phase 1 PoCR, IMT reduced the LOS (-1.02 days; 95% CI = -2.00 to -0.03) and increased exercise capacity (6-minute walk distance) (+75.46 m; 95% CI = 52.34 to 98.57), and maximal inspiratory pressure (MIP) (10.46 cm H2O; 95% CI = 2.83 to 18.10), but had no effect on maximal expiratory pressure. In phase 2 PoCR, IMT increased 6-minute walk distance (45.84 m; 95% CI = 10.89 to 80.80), MIP (-23.19 cm H2O; 95% CI = -31.31 to -15), maximal expiratory pressure (20.18 cm H2O; 95% CI = 9.60 to 30.76), and QOL (-11.17; 95% CI = -17.98 to -4.36), with no effect on peak oxygen uptake. There was a high risk of bias for MIP (75% of the phase 1 studies) and 6MWT (1 of 4 phase 2 studies). The quality of the evidence ranged from very low to moderate. CONCLUSION: IMT significantly improves exercise capacity, respiratory muscle strength, LOS, and QOL in phase 1 and 2 PoCR. IMPACT: IMT may benefit patients during phase 1 and 2 of PoCR, considering the safety, low cost, and potential benefits.

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INTRODUCTION: Along with cardiopulmonary bypass time, aortic cross-clamping time is directly related to the risk of complications after heart surgery. The influence of the time difference between cardiopulmonary bypass and cross-clamping times (TDC-C) remains poorly understood. OBJECTIVE: To assess the impact of cardiopulmonary bypass time in relation to cross-clamping time on immediate results after coronary artery bypass grafting in the Registro Paulista de Cirurgia Cardiovascular (REPLICCAR) II. METHODS: Analysis of 3,090 patients included in REPLICCAR II database was performed. The Society of Thoracic Surgeons outcomes were evaluated (mortality, kidney failure, deep wound infection, reoperation, cerebrovascular accident, and prolonged ventilation time). A cutoff point was adopted, from which the increase of this difference would affect each outcome. RESULTS: After a cutoff point determination, all patients were divided into Group 1 (cardiopulmonary bypass time < 140 min., TDC-C < 30 min.), Group 2 (cardiopulmonary bypass time < 140 min., TDC-C > 30 min.), Group 3 (cardiopulmonary bypass time > 140 min., TDC-C < 30 min.), and Group 4 (cardiopulmonary bypass time > 140 min., TDC-C > 30 min.). After univariate logistic regression, Group 2 showed significant association with reoperation (odds ratio: 1.64, 95% confidence interval: 1.01-2.66), stroke (odds ratio: 3.85, 95% confidence interval: 1.99-7.63), kidney failure (odds ratio: 1.90, 95% confidence interval: 1.32-2.74), and in-hospital mortality (odds ratio: 2.17, 95% confidence interval: 1.30-3.60). CONCLUSION: TDC-C serves as a predictive factor for complications following coronary artery bypass grafting. We strongly recommend that future studies incorporate this metric to improve the prediction of complications.

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INTRODUCTION: The aim of our study is to compare the early and mid-term outcomes of patients with hypertrophic obstructive cardiomyopathy who underwent classic and modified Morrow septal myectomy. METHODS: Between 2014 and 2019, 48 patients (24 males; mean age 49.27±16.41 years) who underwent septal myectomy were evaluated. The patients were divided into two groups - those who underwent classic septal myectomy (n=28) and those who underwent modified septal myectomy (n=20). RESULTS: Mitral valve intervention was higher in the classic Morrow group than in the modified Morrow group, but there was no significant difference (P=0.42). Mortality was found to be lower in the modified Morrow group than in the classic Morrow group (P=0.01). In both groups, the mean immediate postoperative gradient was significantly higher than the mean of the 3rd and 12th postoperative months. The preoperative and postoperative gradient difference of the modified Morrow group was significantly higher than of the classic Morrow group (P<0.001). CONCLUSION: Classic Morrow and modified Morrow procedures are effective methods for reducing left ventricular outflow tract obstruction. The modified Morrow procedure was found to be superior to the classic Morrow procedure in terms of reducing the incidence of mitral valve intervention with the reduction of the left ventricular outflow tract gradient.

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PURPOSE: To identify pharmacological and nonpharmacological interventions adopted for pain relief in the postoperative period of coronary artery bypass graft surgery. DESIGN: Integrative review. METHODS: Studies published in English, Spanish, and Portuguese from January 2010 to December 2019 in Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American and Caribbean Literature on Health Science, PubMed, and Web of Science. Two hundred studies were identified and eleven were included. Methodological analysis was performed using the Medical Education Research Study Quality Instrument. FINDINGS: The studies found were organized into three thematic categories: pharmacological interventions (methadone, morphine, lidocaine gel, remifentanil, sufentanil, and nefopam), nonpharmacological interventions (low-level laser therapy, light-emitting diode, Class IV laser, and transcutaneous nerve stimulation) and anesthetic techniques (dexmedetomidine, ultrasound-guided pectoral nerve block, high thoracic epidural analgesia, and perioperative parasternal block with levobupivacaine). CONCLUSIONS: A greater tendency to use drug strategies for postoperative pain relief was identified. The drugs used demonstrated efficacy and safety in the treatment of pain, with the exception of nefopam, which showed little benefit in this population. Nonpharmacological interventions, used as adjuvants to drug treatment, were shown to be safe, effective, and well tolerated by the patients.

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