First-year profile of biomarkers for early detection of renal injury in infants with congenital urinary tract obstruction.

BACKGROUND: Diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. Use of renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and prevention or minimization of definitive renal damage. METHODS: This longitudinal, prospective study analyzed the first-year profile of two serum renal biomarkers: creatinine (sCr) and cystatin C (sCyC); and six urinary renal biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-ß1), retinol-binding protein (RBP), cystatin C (uCyC), and microalbuminuria (µALB) in a cohort of 37 infants with UTO divided into three subgroups: 14/37 with unilateral hydro(uretero)nephrosis, 13/37 with bilateral hydro(uretero)nephrosis, and 10/37 patients with lower urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. RESULTS: All urine biomarkers showed significantly higher values at the first month of life (p ≤ 0.009), while NGAL (p = 0.005), TGF-ß1 (p < 0.001), and µALB (p < 0.001) were high since birth compared to controls. Best single biomarker performances were RBP in bilateral hydronephrosis and LUTO subgroups and KIM-1 in unilateral hydronephrosis subgroup. Best biomarker combination results for all subgroups were obtained by matching RBP with TGF-ß1 or KIM-1 and NGAL with CyC ([AUC] ≤ 0.934; sensitivity ≤ 92.4%; specificity ≤ 92.8%). CONCLUSIONS: RBP, NGAL, KIM-1, TGF-ß1, and CyC, alone and especially in combination, are relatively efficient in identifying surgically amenable congenital UTO and could be of practical use in indicating on-time surgery.

A First-in-Human Phase I Study of OPB-111077, a Small-Molecule STAT3 and Oxidative Phosphorylation Inhibitor, in Patients with Advanced Cancers.

LESSONS LEARNED: OPB-111077 is a novel inhibitor of STAT3 and mitochondrial oxidative phosphorylation that exhibited promising anticancer activity in preclinical models.In this first-in-human phase I study of OPB-111077 in unselected advanced cancers, treatment-emergent adverse events, most frequently nausea, fatigue, and vomiting, were generally mild to moderate in intensity and could be medically managed.Overall, only modest clinical activity was observed after OPB-111077 given as monotherapy. Notable antitumor activity was seen in a subject with diffuse large B-cell lymphoma. BACKGROUND: OPB-111077 is a novel inhibitor of STAT3 and mitochondrial oxidative phosphorylation with promising anticancer activity in preclinical models. METHODS: Open-label, phase I trial of OPB-111077 in advanced cancers with no available therapy of documented benefit. Initial dose escalation in unselected subjects was followed by dose expansion. Patients received oral OPB-111077 daily in 28-day cycles until loss of clinical benefit. RESULTS: Eighteen subjects enrolled in dose escalation, and 127 in dose expansion. Dose-limiting toxicities were observed at 300 mg and 400 mg QD; maximum tolerated dose was defined as 250 mg QD. Frequently reported treatment-emergent adverse events (TEAEs) included nausea, fatigue, and vomiting. TEAEs were generally mild to moderate and could be medically managed. OPB-111077 reached micromolar drug concentrations, had an elimination half-life of approximately 1 day, and reached steady-state by day 8. A durable partial response was observed in one subject with diffuse large B-cell lymphoma. Seven subjects with diverse tumor types had stable disease or minor responses for at least eight treatment cycles (224 days). CONCLUSION: OPB-111077 is generally well tolerated, and its pharmacokinetic profile is sufficient for further clinical development. Notable clinical activity was observed in a subject with diffuse large B-cell lymphoma. Overall, modest efficacy was observed against unselected tumors.

Combined Impact of Chronic Kidney Disease and Contrast Induced Acute Kidney Injury on Long-term Outcomes in Patients with Acute Lower Limb Ischaemia.

INTRODUCTION: Acute lower limb ischaemia (ALI) is the sudden onset of decreased arterial perfusion with imminent threat to limb viability. Contrast induced acute kidney injury (CI-AKI) is one of the complications that increases mortality in patients who undergo contrast imaging in coronary procedures. The goal of this study is to evaluate the impact of chronic kidney disease (CKD) and CI-AKI on long-term clinical outcomes in patients with ALI undergoing lower limb revascularisation. METHODS: A total 1017 consecutive patients with acute lower limb ischaemia who were admitted between July 1, 2006, and January 1, 2017, were retrospectively reviewed. Patients who had end stage renal disease, those who had end stage heart and malignant disease and died within 7 days of limb revascularisation, and those who did not undergo angiography were excluded. Thus 546 patients were included in the final analysis. Patients were classified as with or without CKD and were then subdivided according to the presence or absence of the development of CI-AKI, defined as an increase in serum creatinine of ≥0.5 mg/dL or by ≥25% from the baseline value within the first 72 h after contrast exposure. The primary end point was all cause mortality and secondary major adverse limb event (MALE). RESULTS: Both CKD and CI-AKI were associated with the highest rate of all cause mortality (chi square = 55.77, d.f. = 1, p < .01, log rank test) and MALE (chi square = 79.07, d.f. = 1, p < .01, log rank test). The presence of CKD and CI-AKI were significant risk factors associated with long-term all cause mortality (HR = 2.61, p < .01) and MALE (HR = 2.87, p < .01). CONCLUSION: In patients with ALI undergoing lower limb revascularisation, both CKD and CI-AKI were significantly associated with poor long-term outcomes compared with either CKD or CI-AKI alone. Further studies are required to assess this association and to confirm the combined effect of CKD and CI-AKI on long-term clinical outcomes.

Effects of atmospheric pressure dynamics on abdominal aortic aneurysm rupture onset.

BACKGROUND: The effect of atmospheric pressure (AP) on the onset of abdominal aorta aneurysm rupture (RAAA) remains an unanswered question. We have investigated the seasonal variation and the effect of AP dynamics on RAAA by analysing the largest series of intraoperatively confirmed RAAA. PATIENTS AND METHODS: To realize this study we have performed a retrospective analysis of 546 patients with RAAA, operated within 503 days at the Clinic for vascular and endovascular surgery CCS between 1.1.2003 and 31.12.2012. AP data for Belgrade city were obtained from meteorological yearbooks published by the Republic Hydrometeorological Service of Serbia measured at the hydrometeorological station "Belgrade Observatory". Only patients with a residence within the extended Belgrade region, exposed to the similar AP values, were included in the analysis of the AP effect on RAAA. RESULTS: RAAA were observed more frequently during winter and autumn months but without significant difference in comparison to other seasons. Months with higher AP values were associated with a higher RAAA rate (p = 0.0008, R2 = 0.665). A similar trend was observed for the monthly AP variability (p = 0.0311, R2 = 0.374). Average AP values did not differ between days with and without RAAA. However, during the three and seven days periods preceding RAAA AP variability parameters were greater and AP was rising. CONCLUSIONS: Although these pressure differences are very small, higher AP values over longer periods of time as well as greater variability are associated with RAAA. The exact mechanism behind this association remains unclear. The postulation that low AP may precipitate RAAA based on the Laplace law should be discarded.

Bilateral Internal Carotid Artery Occlusion, External Carotid Artery Stenosis, and Vertebral Artery Kinking: May It Be Asymptomatic?

The clinical spectrum of internal carotid artery occlusion ranges from being a completely asymptomatic occlusion to a devastating stroke or death. The prevalence of asymptomatic internal carotid artery occlusion is unknown, particularly for bilateral occlusion. The distal branches of the external carotid artery anastomose with distal branches of the internal carotid artery provide important sources of collateral circulation to the brain. Stenosis of the external carotid artery with ipsilateral/bilateral internal occlusion may result in ischemic sequelae. Coiling or kinking of the vertebral artery is a rare morphological entity that is infrequently reported because it remains asymptomatic and has no clinical relevance. Currently, there is little evidence to support management strategies for this disease entity and no official recommendations for asymptomatic bilateral carotid artery occlusion. We present a case of a 62-year-old female with asymptomatic bilateral internal carotid artery occlusion, bilateral external carotid artery stenoses, and bilateral kinking of the vertebral artery at the V2 segment, who has been successfully managed conservatively for over 5 years. An individualized approach to management of patients with bilateral internal carotid artery occlusion, especially in combination with external carotid artery stenosis and elongation malformations of the vertebral artery is key to a successful strategy.

Carotid replacement with Dacron graft in 292 patients.

INTRODUCTION: In case of highly atherosclerotic carotid process, carotid graft replacement might be a potential solution for successful procedure. Many studies evaluated the results of vein and polytetrafluorethilen (PTFE) graft usage at the carotid bifurcation, while the experience on the Dacron graft due to extensive atherosclerotic process is missing. The aim of our study was to evaluate 30-day and long-term results of the Dacron graft on carotid artery used in patients with extensive atherosclerotic disease. MATERIAL AND METHODS: This retrospective study analysed early and long-term neurological outcome as well as Dacron graft patency in patients operated with carotid reconstruction. Early results were confirmed by follow-up clinical examination, whereas late results were assessed by follow-up clinical examination as well as duplex sonographic examination at least 1 year after the surgery. As for statistical methods we used descriptive analysis tests, Chi-square test, and logistic regression. RESULTS: Carotid graft replacement was performed in 292 patients, before endarterectomy in 155 (53.09%), or after already attempted unsuccessful eversion endarterectomy in 137 (46.91%). Nineteen (6.5%) patients had a stroke due to ipsilateral and contralateral ischaemia or haemorrhagic in 17 (5.8%), 1 (0.3%) and 1 (0.3%) patients, respectively. Significantly higher rate of strokes occurred when the graft reconstruction was used after the failure of endarterectomy (8.5% vs. 3.5%, p = 0.029). Stroke and death rate was 7.19%. Factors that increased risk of early stroke were the length of plaque in the internal carotid artery measured intraoperatively (p = 0.025) and the surgical tactic to perform graft reconstruction after attempted extensive endarterectomy (p = 0.029). CONCLUSION: Low number of patients with carotid stenosis has extensive atherosclerotic process longer than 4 cm that might jeopardise eversion endarterectomy. Carotid graft replacement with Dacron graft provide early results that are comparable with other conduits; however, in such patients reconstruction should be selected individually based on surgical experience and anatomical distribution of stenotic disease. Due to high risk of stroke, only symptomatic patients with such extensive atherosclerotic disease should be operated.

Clinical course of patients with hyponatremia and decompensated systolic heart failure and the effect of vasopressin receptor antagonism with tolvaptan.

BACKGROUND: Patients with decompensated heart failure, volume overload, and hyponatremia are challenging to manage. Relatively little has been documented regarding the clinical course of these patients during standard in-hospital management or with vasopressin antagonism. METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan database was examined to assess the short-term clinical course of patients hospitalized with heart failure and hyponatremia and the effect of tolvaptan on outcomes. In the placebo group, patients with hyponatremia (serum Na(+) <135mEq/L; n = 232), compared with those with normonatremia at baseline (n = 1785), had less relief of dyspnea despite receiving higher doses of diuretics (59.2% vs 69.2% improved; P < .01) and worse long-term outcomes. In the hyponatremia subgroup from the entire trial cohort (n = 475), tolvaptan was associated with greater likelihood of normalization of serum sodium than placebo (58% vs 20% and 64% vs 29% for day 1 and discharge, respectively; P < .001 for both comparisons), greater weight reduction at day 1 and discharge (0.7 kg and 0.8 kg differences, respectively; P < .001 and P = .008), and greater relief of dyspnea (P = .03). Among all hyponatremic patients, there was no effect of tolvaptan on long-term outcomes compared with placebo. In patients with pronounced hyponatremia (<130 mEq/L; n = 92), tolvaptan was associated with reduced cardiovascular morbidity and mortality after discharge (P = .04). CONCLUSIONS: In patients with decompensated heart failure and hyponatremia, standard therapy is associated with less weight loss and dyspnea relief, and unfavorable longer-term outcomes compared to those with normonatremia. Tolvaptan is associated with more favorable in-hospital effects and, possibly, long-term outcomes in patients with severe hyponatremia.

Treatment of vascular non-iatrogenic injuries of upper and lower extremities in tertiary vascular center.

BACKGROUND: The purpose of this study was to examine demographic and baseline characteristics of patients with vascular injuries of extremities and to define the most relevant factors which influenced an early outcome, as well as limb salvage after the management of vascular trauma. METHODS: This study used the database that included 395 patients with peripheral arterial injuries, who were treated in the tertiary vascular university center in the period between 2005-2020. Exclusion criteria were isolated thoracic, abdominal and neck injuries as well as iatrogenic injuries and injuries of intravenous addicts. Univariate binary logistic regression analysis and multiple logistic regression were used to determine risk factors for lomb loss (after vascular reconstruction) or mortality. Decision to perform primary amputation (without vascular reconstruction) was based on surgeons' preference and experience. RESULTS: Out of 395 vascular injuries treated in the period 2005-2020, 210 (53.2%) presented with non-iatrogenic vascular injuries of upper and lower extremities were analyzed. According to the univariate regression analysis, hemorrhage as the main clinical manifestation on admission (P=0.035) and early reintervention (P=0.048) increased, while an early patency of repaired artery (0.010) significantly decreased a 30-day amputation rate. Multivariate logistic regression analysis of these three variables showed that only early patency of repaired artery significantly decreased the early amputation rate (P=0.009). CONCLUSIONS: Based on presented experience, the patency of vascular reconstruction plays a crucial role in limb salvage in patients with non-iatrogenic peripheral vascular injuries. All factors that might influence the patency should be in focus of improvement.

Surgical treatment of carotid restenosis after eversion endarterectomy--Serbian bicentric prospective study.

BACKGROUND: The increased number of carotid endarterectomies performed worldwide in recent years is associated with a greater need for carotid restenosis evaluation. Carotid restenosis rate ranges from 0.6% to 3.6% in symptomatic patients and from 8.8% to 19% in asymptomatic patients. Carotid angioplasty and stenting is a preferable therapeutic choice for carotid restenosis treatment, but whenever it is not technically feasible (tortuosities of supra-aortic branches, calcifications, pathological elongation, or very extensive lesions), redo surgical treatment is indicated. The aim of our study was to examine outcome of redo surgical treatment in patients with symptomatic and asymptomatic carotid restenosis, in whom carotid angioplasty could not be done, and its impact on early and late morbidity and mortality. METHODS: The study included 52 patients who were surgically treated for significant carotid restenosis from January 2000 to December 2008 in two high-volume vascular surgery university clinics. Surgical techniques included redo eversion endarterectomy, standard endarterectomy with Dacron patch closure, and Dacron tubular graft interposition. The patients were followed for significant events (transient ischemic attack, stroke, cranial nerve injuries, surgical site hematoma, the occurrence of carotid re-restenosis, or occlusion), and mortality after 1 month, 6 months, 1 year, and annually afterward. RESULTS: In the early postoperative period (within 30 days), there were no lethal outcomes. Transient ischemic attack was diagnosed in four patients (7.6%), minor stroke in two patients (3.8%), and cranial nerve injury in four patients (7.6%). After 4 years, three patients died (5.7%), two due to a fatal myocardial infarction (3.8%) and one after a major stroke (1.9%); four patients (7.6%) had ipsilateral stroke; and graft occlusion was verified in one patient (1.9%). CONCLUSION: Carotid angioplasty might be a primary option for carotid restenosis treatment, but whenever it cannot be performed, redo surgical treatment is indicated, owing to its acceptable rate of early and late postoperative complications.

Role of recombinant factor VIIa in the treatment of intractable bleeding in vascular surgery.

BACKGROUND: Most recent publications have shown that the recombinant form of activated factor VII (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsværd, Denmark) induces excellent hemostasis in patients with severe intractable bleeding caused by trauma and major surgery. The purpose of this study was to determine the influence of rFVIIa on the treatment of intractable perioperative bleeding in vascular surgery when conventional hemostatic measures are inadequate. MATERIALS AND METHODS: There were two groups of patients: the NovoSeven group (group N), 10 patients with ruptured abdominal aortic aneurysms (RAAAs) and 14 patients operated on due to thoracoabdominal aortic aneurysms (TAAAs); the control group (group C), 14 patients with RAAAs and 17 patients with TAAAs. All patients suffered intractable hemorrhage refractory to conventional hemostatic measures, while patients from group N were additionally treated with rFVIIa. RESULTS: Postoperative blood loss was significantly lower in group N treated with rFVII (P < .0001). Postoperative administration of packed red blood cells, fresh frozen plasma, and platelets was lower in patients from group N, (P < .0001). Successful hemorrhage arrest was reported in 21 patients (87.5%) treated with rFVIIa, and in 9 patients (29.03%) in group C (P < .001). Thirty-day mortality in these two groups significantly differed. The mortality rate was 12.5% (3 patients) in group N and 80.65% (25 patients) in group C (P < .0001). CONCLUSION: Our findings suggest that rFVIIa may play a role in controlling the intractable perioperative and postoperative bleeding in surgical patients undergoing a repair of RAAAs and TAAAs. Certainly, prospective randomized trials are necessary to further confirm the efficacy and cost-effectiveness of rFVIIa in these patients.

Twenty years of experience in the treatment of spontaneous aorto-venous fistulas in a developing country.

BACKGROUND: One of the rare forms of abdominal aortic aneurysm (AAA) rupture is the rupture into great abdominal veins such as the inferior vein cava (IVC), the iliac veins, or the left renal vein, with the formation of direct or indirect aorto-caval fistula (ACF). The purpose of the present study was to summarize 20 years of experience at a single referral center for vascular surgery in a developing country, and to discuss the clinical presentation, diagnosis, treatment options, and outcome of patients with spontaneous aorto-venous fistulas (AVF) caused by ruptured aortic aneurysms. MATERIALS AND METHODS: Retrospective database review identified 50 patients treated in our institution for aorto-venous fistulas (AVF) caused by spontaneous AAA rupture in the 20 years 1991-2010. Pulsating abdominal mass and low back pain were the leading symptoms on admission in our patients. Signs of shock, congestive heart failure, or pelvic and lower extremity venous hypertension were present in 48%, 26%, and 75% of the patients, respectively. Diagnosis of AVF was based on physical examination, duplex ultrasonography, conventional angiography, or multislice computed tomography (MSCT). In 40% of the patients the presence of AVF has not been recognized before surgery. All patients were treated with open surgery. RESULTS: After proximal and distal bleeding control the fistula was closed with direct suture (92%) or patch angioplasty (8%). Aortic reconstruction followed with tubular (22%) or bifurcated (78%) synthetic graft. Six (12%) patients died. The causes of death were excessive intraoperative blood loss, myocardial infarction, left colon gangrene and multiple organ failure. CONCLUSIONS: Spontaneous AVFs caused by aneurysmal rupture are not uncommon, and they require prompt surgical or endovascular treatment. Routine use of multislice CT in patients with acute aortic syndrome is probably the best way to the correct diagnosis of aorto-venous fistulas and planning of the optimal treatment.

Flow-through peritoneal dialysis in neonatal enema-induced hyperphosphatemia.

Fleet enemas are hypertonic solutions with an osmotic action and a high concentration of phosphate. When retained in the human body they have a great toxic potential, causing severe hydro-electrolyte disorders in children, especially in newborns. We report the case of a previously healthy 8-day-old newborn who needed neonatal intensive care treatment after the inadvertent administration of an osmotically active hypertonic phosphate enema. Taking into account that phosphate removal by peritoneal dialysis (PD) strongly depends on total dialysate turnover, we chose continuous flow PD (CFPD) as the treatment option, with a successful outcome. Clinical experience with this dialytic modality is limited to a few case reports in pediatric and adult patients. To the best of our knowledge, we report here the first description of CFPD in the setting of acute phosphate nephropathy in the neonatal period. The modality of PD described here has potential as an alternative management option as it is a highly efficient, methodologically simple, and low-cost method without any need for sophisticated equipment. Physicians and parents should be aware of the adverse effects of a hypertonic phosphate enema and should never use these medications in infants and newborns.

Open repair of ruptured abdominal aortic aneurysm with associated horseshoe kidney.

BACKGROUND: Ruptured abdominal aortic aneurysms (RAAA) with concomitant horseshoe kidney (HK) present a unique challenge at the time of repair. The aim of this article was to propose the most rationale strategy during open repair (OR) of RAAA in the presence of HK. METHODS: We identified and analyzed all patients treated at the clinic due to RAAA and HK. An extensive search was performed on all articles published up to August of 2017 describing open and endovascular repair of RAAA with concomitant horseshoe kidney. The following data were extracted and analyzed: patient number, number of renal arteries, Crawford classification of horseshoe kidney vascularization, type of aortic reconstruction, management with renal arteries, 30-day kidney failure and outcome. RESULTS: Transperitoneal approach followed by supraceliac aortic cross clamping without the division of the renal isthmus occurred in all our six cases. Four of them required additional procedures with accessory renal arteries after aortic replacement. Three of patients (50%) died during the first 30 postoperative days, while one developed transitory renal insufficiency. The renal isthmus was preserved in 43.90% and divided in 46.34% of cases. Crawford type I of HK vascularization was presented in 21.95% of cases, type II also in 39.02%, while the type III in 19.51% of cases. In 46.33% of cases a procedure with renal arteries was necessary. In 26.82% accessory renal arteries were ligated, while in 19.51% preserved (reattachment or aorto-renal bypass). Thirty-day mortality was 21.95%, while the incidence of postoperative renal failure was also 21.95%. There was not significant correlation between the renal artery ligation and the postoperative renal failure (r=-0.81, P=0.59). CONCLUSIONS: Transperitoneal approach should be preferred during urgent OR of RAAA with concomitant HK. A supraceliac aortic cross clamping and the placement of occlusive Fogarty catheters into both iliac arteries are recommended for proximal and distal bleeding control. Preservation of accessory renal arteries that are larger than 3 mm in diameter or supply more than 30% of renal parenchima is recommended. The division of the renal isthmus should be avoided if vascularized. It seems that renal arteries could be covered in emergency EVAR without any implications on postoperative kidney function, allowing broader aplication of endovascular treatment for thesse patients.

Severity of memory impairment in the elderly: Association with health care resource use and functional limitations in the United States.

INTRODUCTION: Dementia is a prevalent condition in older adults associated with decline in cognitive and functional abilities and substantial burden. This study assessed the prevalence and impact of subjective memory impairment in the United States. METHODS: The 2011 to 2014 National Health and Nutrition Examination Survey, a population-based, nationally representative survey, was analyzed. Data included medical examinations, self-reported cognitive and functional limitations, and health care utilization over 1 year. Participants were aged ≥65 years and completed both interview and medical examination components. Descriptive analyses of patient characteristics were performed, and complex survey regression models were used to test associations. RESULTS: Of 2431 survey participants included, 53.1% had no memory impairment, 40.1% had early-stage memory impairment, and 6.6% had late-stage memory impairment. In adjusted analyses, late-stage versus no impairment was associated with more functional limitations (odds ratio [OR] = 7.26, P < .001), greater health care utilization (OR = 2.46, P < .001), and higher likelihood of seeing a mental health specialist (OR = 3.06, P = .001). DISCUSSION: Consistent with previous research, individuals with late-stage memory impairment had significantly greater functional limitations and higher health care utilization versus individuals with early-stage or no memory impairment.

Blood groups and acute aortic dissection type III.

INTRODUCTION: Acute aortic type III dissection is one of the most catastrophic events, with in-hospital mortality ranging between 10% and 12%. The majority of patients are treated medically, but complicated dissections, which represent 15% to 20% of cases, require surgical or thoracic endovascular aortic repair (TEVAR). For the best outcomes adequate blood transfusion support is required. Interest in the relationship between blood type and vascular disease has been established. The aim of our study is to evaluate distribution of blood groups among patients with acute aortic type III dissection and to identify any kind of relationship between blood type and patient's survival. MATERIAL AND METHODS: From January 2005 to December 2014, 115 patients with acute aortic type III dissection were enrolled at the Clinic of Vascular and Endovascular Surgery in Belgrade, Serbia and retrospectively analyzed. Patients were separated into two groups. The examination group consisted of patients with a lethal outcome, and the control group consisted of patients who survived. RESULTS: The analysis of the blood groups and RhD typing between groups did not reveal a statistically significant difference (p = 0.220). CONCLUSIONS: Our results indicated no difference between different blood groups and RhD typing with respect to in-hospital mortality of patients with acute aortic dissection type III.

A prospective, multicenter, randomized, parallel-group, open-label study of aripiprazole in the management of patients with schizophrenia or schizoaffective disorder in general psychiatric practice: Broad Effectiveness Trial With Aripiprazole (BETA).

OBJECTIVE: BETA was designed to evaluate the overall effectiveness of aripiprazole in patients with schizophrenia or schizoaffective disorder treated in a general psychiatry outpatient practice setting. METHODS: In this 8-week, multicenter, open-label study, 1,599 outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive either aripiprazole (n=1,295) or another antipsychotic medication (safety control [SC] group; n=304). Aripiprazole was initiated at 15 mg/d with the option to adjust between 10-30 mg/d. The SC medication was specifically selected for each patient by the clinician and dosed according to prescribing guidelines for that medication. The primary effectiveness measure was the Clinical Global Impression-Improvement (CGI-I) score of the aripiprazole group at study end point. Secondary measures included response rates and preference of medicine (POM) ratings by patients and caregivers. RESULTS: Sixty-five percent of aripiprazole patients completed the study. The mean aripiprazole dose at end point was 19.9 mg/d, with approximately 39% of patients starting and remaining at 15 mg/d. At end point, the mean CGI-I score of 2.77 demonstrated that aripiprazole was minimally to moderately effective; the mean CGI-I score for the SC group was 3.59 indicating minimally effective to no change. Fifty-three percent of aripiprazole patients responded to treatment (CGI-I score of 1 or 2; last-observation-carried-forward [LOCF]), and approximately 71% of patients and caregivers rated aripiprazole as better than the prestudy medication on the POM (LOCF). Incidence and severity of adverse events (AEs) were similar to those reported in double-blind, randomized, placebo-controlled aripiprazole clinical trials. The most frequent AE in the aripiprazole group was insomnia (24%). CONCLUSIONS: Aripiprazole was effective for the treatment of schizophrenia and schizoaffective disorder in a general psychiatry outpatient practice setting. Overall, aripiprazole was found to be effective by the treating clinician and well accepted by patients and caregivers over the 8-week treatment course.

Efficacy of aripiprazole against hostility in schizophrenia and schizoaffective disorder: data from 5 double-blind studies.

OBJECTIVE: The objective was to determine the effects of aripiprazole on hostility. METHOD: A total of 1476 patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder were the subjects in 5 short-term, double-blind studies comparing aripiprazole with placebo; 3 of these studies also included a comparison with haloperidol. The studies were conducted between December 1993 and January 2001. The Positive and Negative Syndrome Scale (PANSS) was the principal outcome measure in these studies. To determine the effect of aripiprazole on hostility, post hoc analyses of the hostility item from the PANSS were conducted for the first 4 weeks of treatment. RESULTS: Aripiprazole was superior to placebo and not significantly different from haloperidol in reducing hostility. CONCLUSION: Aripiprazole is an effective treatment for hostility in patients with schizophrenia or schizoaffective disorder.