Large-volume Paracentesis versus Dialytic Ultrafiltration in the Treatment of Cirrhotic Ascites

We compared the clinical efficacy and safety of large-volumeparacentesis and dialytic ultrafiltration in the treatment ofrefractory ascites in cirrhotic patients. A group of cirrhoticsubjects (age 49–80 years) were randomly allocated toeither continuous paracentesis (1–1.5 1/hour) or dialyticultrafiltration until disappearance of ascites. Each patientwas maintained on bed rest, fluid restriction (1 1/day) anda low (25 mmol/day) sodium diet for 14 days. Five patients (threein the paracentesis group and two in dialytic ultrafiltrationgroup) developed massive ascites 3–5 months later, andreceived the crossover treatment. The average volume of fluidremoved was similar in the two groups (4.70±1.47 1 fordialytic ultrafiltration versus 4.69±1.84 1 for paracentesis),but the treatment period was significantly shorter with dialyticultrafiltration. The plasma creatinine significantly increasedthree days after paracentesis but did not increase in patientstreated with dialytic ultrafiltration. There was an initialfall in mean arterial pressure during the first two hours ofeither treatment; a further fall in blood pressure was observedwith paracentesis but not with dialytic ultrafiltration. Pretreatmentplasma renin activity was elevated, but was not altered by eithertreatment. Plasma atrial natriuretic peptide levels were inthe high-normal range before treatment. Paracentesis was associatedwith a delayed fall in plasma atrial natriuretic peptide, whiledialytic ultrafiltration induced a modest but significant rise.No complication was experienced with dialytic ultrafiltrationin the two weeks following treatment, but four of the eightpatients who underwent paracentesis had developed severe complications.Dialytic ultrafiltration of ascitic fluid is a safe procedurein cirrhotic patients. Large-volume paracentesis without intravenouscolloid reinfusion causes complications and carries the potentialrisk of reducing the effective intravascular volume.     

Barriers to the effective management of bipolar disorder: a survey of psychiatrists based in the UK and USA

Objective:  To identify and prioritize barriers, challenges, and unmet needs in the management of patients with bipolar disorder, as perceived by their psychiatrists.
Methods:  A total of 500 US- or UK-based psychiatrists were surveyed by telephone using a validated, semi-structured questionnaire. Both preidentified and participant-elicited barriers, challenges and unmet needs were ranked on a 0–6 point scale in four phases of management: I, entry into care; II, the manic/hypomanic phase; III, the depressive phase; and IV, the long-term/maintenance phase.
Results:  Education and support for patients and families as well as earlier referral to specialist care were the highest ranked needs at entry into care. During treatment of acute episodes and long-term management the highest ranked needs were for treatments with improved effectiveness and patient adherence, in addition to improved long-term safety in the maintenance phase. Patients with comorbid alcohol and/or substance use disorders, followed by patients with a rapid-cycling disease course, were rated as having the highest level of unmet need. Similarities were predominantly seen between the overall pattern of responses from UK- and US-based psychiatrists.
Conclusions:  The highest priority items across the spectrum of treatment related to the need for clinically effective therapeutic agents with broad efficacy and favorable tolerability. At the time of initial diagnosis, patient education, family support, and earlier referral to specialist care were the highest priority needs.     

Automated differentiation of glioblastomas from intracranial metastases using 3T MR spectroscopic and perfusion data

Purpose   Differentiation of glioblastomas from metastases is clinical important, but may be difficult even for expert observers. To investigate the contribution of machine learning algorithms in the differentiation of glioblastomas multiforme (GB) from metastases, we developed and tested a pattern recognition system based on 3T magnetic resonance (MR) data. Materials and Methods   Single and multi-voxel proton magnetic resonance spectroscopy (1H-MRS) and dynamic susceptibility contrast (DSC) MRI scans were performed on 49 patients with solitary brain tumors (35 glioblastoma multiforme and 14 metastases). Metabolic (NAA/Cr, Cho/Cr, (Lip  $+$  Lac)/Cr) and perfusion (rCBV) parameters were measured in both intratumoral and peritumoral regions. The statistical significance of these parameters was evaluated. For the classification procedure, three datasets were created to find the optimum combination of parameters that provides maximum differentiation. Three machine learning methods were utilized: Naïve-Bayes, Support Vector Machine (SVM) and $k$ -nearest neighbor (KNN). The discrimination ability of each classifier was evaluated with quantitative performance metrics. Results   Glioblastoma and metastases were differentiable only in the peritumoral region of these lesions ( $p<0.05$ ). SVM achieved the highest overall performance (accuracy 98 %) for both the intratumoral and peritumoral areas. Naïve-Bayes and KNN presented greater variations in performance. The proper selection of datasets plays a very significant role as they are closely correlated to the underlying pathophysiology. Conclusion   The application of pattern recognition techniques using 3T MR-based perfusion and metabolic features may provide incremental diagnostic value in the differentiation of common intraaxial brain tumors, such as glioblastoma versus metastasis.     

A phase II trial of arsenic trioxide and temozolomide in combination with radiation therapy for patients with malignant gliomas

Standard treatment for GBM is radiation (RT) and temozolomide (TMZ). Arsenic trioxide (ATO) is synergistic with RT based on several mechanisms of action previously identified, however not tested herein. The MTD of ATO, RT and TMZ was determined in a Phase I trial. We now present the combined Phase I/II data. Patients with newly diagnosed malignant gliomas were eligible for treatment. Patients were treated with RT (60 GY), TMZ (75 mg/m² daily?×?42 days) and ATO 0.20 mg/kg daily in week 1 then twice a week ×5 weeks, after completing RT they were treated with TMZ 5/28 for up to 12 months. MRIs were performed every 8 weeks. A total of 42 patients were enrolled in both the Phase I and II trials for this study treatment. Of the 42 enrolled patients (24 M and 18 W) the median age was 54 (24–80) and median KPS 90 (60–100). 28 patients had a GBM and 14 had anaplastic glioma (AG). All patients completed RT/TMZ/ATO and went on to maintenance TMZ. Median number of post RT cycles of TMZ was 4 (0–12). Median PFS was 7 m for GBM and 75 m for AG and median OS was 17 m for GBM and NR for AG. Best response was CR in 2, SD in 28, PR in 5 and PD in 7. There were no unexpected adverse events. Grade 3 toxicities likely attributable to ATO included prolonged Qtc (n?=?1), elevated liver enzymes (n?=?2 for ALT/n =?1 for AST) and elevated bilirubin (n?=?1). Adding ATO to RT and TMZ is feasible with no increased side effects. The addition of arsenic did not improve overall survival in the GBM patients as compared to historic data. MGMT status was analyzed in 20 of the 42 patients where tissue was available for retrieval and MGMT testing.     

Upper urinary tract calculi: extrusion into perinephric and periureteric tissues during percutaneous management

While the goal of percutaneous management of renal and ureteral calculi is stone extraction or disintegration, perforation of the renal pelvis or ureter may allow stones or stone fragments to become extruded during endourologic manipulations. The authors have encountered six such patients: two with renal and four with ureteral calculi. Three stones were extruded into the perinephric or periureteric tissues during nephroscopy, two during attempted dislodgement with a balloon catheter, and one during antegrade passage of a ureteral catheter. All patients were managed conservatively by means of nephrostomy drainage and, in the four cases of ureteral laceration, ureteral stenting. Follow-up study, ranging from 12 to 24 months, has documented a benign clinical and radiological course. No ureteral strictures have ensued. In the absence of infected urine, urothelial laceration with calculus extrusion appears to be a benign occurrence and may be managed conservatively.     

Increased airway responsiveness in children of low birth weight at school age: effect of topical corticosteroids

The effect of treatment with topical inhaled corticosteroids was assessed in 15 children of low birth weight (mean (SD) birth weight 1435 (268) g, gestational age 30.5 (2.9) weeks, age at study 8.2 (0.4) years) who were symptomatic and showed a positive airway response to histamine aerosol. The study was of a double blind, placebo controlled, crossover design with four week long treatment periods with inhaled beclomethasone dipropionate (400 micrograms daily) or placebo. Daily symptom scores were recorded and physiological measurements were performed at the beginning and end of each treatment period. There was no significant difference in respiratory symptom score, baseline airway function, or the airway response to histamine between treatment periods. The findings argue against an inflammatory basis for airway hyper-responsiveness in these children and raise questions as to its pathophysiological basis.