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Mean Dose (mean + dose)
Selected AbstractsCitalopram treatment of social anxiety disorder with comorbid major depressionDEPRESSION AND ANXIETY, Issue 4 2003Franklin R. Schneier M.D. Abstract Treatment of patients with both social anxiety disorder and major depression has been little studied although social anxiety disorder and depression frequently co-occur. Each disorder has been shown to respond to serotonin reuptake inhibitor treatment. Objectives of this study were to characterize a sample of these comorbid patients and to assess response to treatment with citalopram. Patients with primary DSM-IV generalized subtype of social anxiety disorder and comorbid major depression (N = 21) were assessed for symptoms of each disorder, including atypical depressive features, and functional impairment. Patients were treated with a flexible dose of open label citalopram for 12 weeks. Response rates for the intention-to-treat sample at week 12 were 14/21 (66.7%) for social anxiety disorder and 16/21 (76.2%) for depression. All continuous measures of social anxiety, depression, and functional impairment improved significantly with treatment, but depression symptoms responded more rapidly and more completely than social anxiety symptoms. Mean dose of citalopram at study endpoint was 37.6 mg/day. Only three patients (14.3%) fulfilled DSM-IV criteria for atypical features of depression, although 18 (85.7%) fulfilled the criterion for interpersonal rejection sensitivity. Citalopram treatment may benefit patients with primary social anxiety disorder and comorbid major depression, and it should be further studied in controlled trials. Improvement in social anxiety disorder symptoms lagged behind improvement in depression, and greater than 12 weeks of treatment may be required to assess full social anxiety response in patients with comorbid depression. The overlap of social anxiety disorder with atypical features of depression may primarily be due to the shared feature of rejection sensitivity. Depression and Anxiety 17:191,196, 2003. © 2003 Wiley-Liss, Inc. [source] Emergency Department Use of Intravenous Procainamide for Patients with Acute Atrial Fibrillation or FlutterACADEMIC EMERGENCY MEDICINE, Issue 12 2007Ian G. Stiell MD Objectives Acute atrial fibrillation and flutter are very common arrhythmias seen in emergency department (ED) patients, but there is no consensus for their optimal management. The objective of this study was to examine the efficacy and safety of intravenous (IV) procainamide for acute atrial fibrillation or flutter. Methods This health records review included a consecutive cohort of ED patients with acute-onset atrial fibrillation or atrial flutter who received IV procainamide at one university hospital ED during a five-year period. The standard clinical protocol involved IV infusion of 1 g of procainamide over 60 minutes, followed by electrical cardioversion if necessary. A trained observer extracted data from the original clinical records. Outcome measurements included conversion to sinus rhythm, adverse events, and relapse up to seven days. Results The 341 study patients had a mean age of 63.9 years (SD ± 15.5 years), and 56.6% were male. The conversion rates were 52.2% (95% confidence interval = 47% to 58%) for 316 atrial fibrillation cases and 28.0% (95% confidence interval = 13% to 46%) for 25 atrial flutter cases. Mean dose given was 860.7 mg (SD ± 231.2 mg), and median time to conversion was 55 minutes. Adverse events occurred in 34 cases (10.0%): hypotension, 8.5%; bradycardia, 0.6%; atrioventricular block, 0.6%; and ventricular tachycardia, 0.3%. There were no cases of torsades de pointes, cerebrovascular accident, or death. Most patients (94.4%) were discharged home, but 2.9% of patients returned with a recurrence of atrial fibrillation within seven days. Conclusions This study of acute atrial fibrillation or flutter patients treated in the ED with IV procainamide suggests that this treatment is safe and effective in this setting. Procainamide should be prospectively compared with other ED strategies. [source] Open trial of nefazodone among Hispanics with major depression: Efficacy, tolerability, and adherence issuesDEPRESSION AND ANXIETY, Issue 3 2001J. Arturo Sánchez-Lacay M.D., M.P.H. Abstract The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score ,18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with ,1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58,69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD=170), also within the range of previous trials (321,472mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by >6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21,33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports. Depression and Anxiety 13:118,124, 2001. © 2001 Wiley-Liss, Inc. [source] Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapyDIABETES OBESITY & METABOLISM, Issue 2 2009E. Ferrannini Aim:, To examine the efficacy and safety of vildagliptin vs. glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus in a 52-week interim analysis of a large, randomized, double-blind, multicentre study. The primary objective was to demonstrate non-inferiority of vildagliptin vs. glimepiride in glycosylated haemoglobin (HbA1c) reduction at week 52. Methods:, Patients inadequately controlled on metformin monotherapy (HbA1c 6.5,8.5%) and receiving a stable dose of metformin (mean dose 1898 mg/day; mean duration of use 36 months) were randomized 1:1 to receive vildagliptin (50 mg twice daily, n = 1396) or glimepiride (titrated up to 6 mg/day; mean dose 4.5 mg/day, n = 1393). Results:, Non-inferiority of vildagliptin was demonstrated (97.5% confidence interval 0.02%, 0.16%) with a mean (SE) change from baseline HbA1c (7.3% in both groups) to week 52 endpoint of ,0.44% (0.02%) with vildagliptin and ,0.53% (0.02%) with glimepiride. Although a similar proportion of patients reached a target HbA1c level of <7% with vildagliptin and glimepiride (54.1 and 55.5%, respectively), a greater proportion of patients reached this target without hypoglycaemia in the vildagliptin group (50.9 vs. 44.3%; p < 0.01). Fasting plasma glucose (FPG) reductions were comparable between groups (mean [SE] ,1.01 [0.06] mmol/l and ,1.14 [0.06] mmol/l respectively). Vildagliptin significantly reduced body weight relative to glimepiride (mean [SE] change from baseline ,0.23 [0.11] kg; between-group difference ,1.79 kg; p < 0.001) and resulted in a 10-fold lower incidence of hypoglycaemia than glimepiride (1.7 vs. 16.2% of patients presenting at least one hypoglycaemic event; 39 vs. 554 hypoglycaemic events, p < 0.01). No severe hypoglycaemia occurred with vildagliptin compared with 10 episodes with glimepiride (p < 0.01), and no patient in the vildagliptin group discontinued because of hypoglycaemia compared with 11 patients in the glimepiride group. The incidence of adverse events (AEs), serious AEs and adjudicated cardiovascular events was 74.5, 7.1 and 0.9%, respectively, in patients receiving vildagliptin, and 81.1, 9.5 and 1.6%, respectively, in patients receiving glimepiride. Conclusions:, When metformin alone fails to maintain sufficient glycaemic control, the addition of vildagliptin provides comparable efficacy to that of glimepiride after 52 weeks and displays a favourable AE profile, with no weight gain and a significant reduction in hypoglycaemia compared with glimepiride. [source] Vigabatrin and Epilepsy: Lessons LearnedEPILEPSIA, Issue 7 2007John M. Wild Summary:,Purpose: The risk factors for visual field loss attributable to vigabatrin (VAVFL) are equivocal. This multinational, prospective, observational study aimed to clarify the principal/major factors for VAVFL. Methods: Interim analysis of three groups with refractory partial epilepsy, stratified by age (8,12 years; >12 years) and exposure to vigabatrin (VGB). Group I comprised participants treated with VGB for ,6 months, Group II participants previously treated with VGB for ,6 months who had discontinued the drug for ,6 months and Group III those never treated with VGB. Perimetry was undertaken at least every six months, for up to 36 months; results were evaluated masked to drug exposure. Results: Based upon 563 participants in the locked data set, 432 yielded one or more Conclusive visual field examinations. For Group I, the frequency of VAVFL at the last Conclusive examination was 10/32 (31.2%) for those aged 8,12 years and 52/125 (41.6%) for those aged >12 years. For Group II, the proportions were 4/39 (10.3%) and 31/129 (24.0%). No cases resembling VAVFL manifested in Group III. VAVFL was associated with duration of VGB therapy (Odds ratio [OR] 14.2; 95% CI 5.0 to 40.5); mean dose of VGB (OR 8.5; 95% CI 2.2 to 33.2); and male gender (OR 2.1; 95% CI 1.2 to 3.7). VAVFL was more common with static than kinetic perimetry (OR 2.3, 95% CI 1.3 to 4.2). Conclusions: The therapeutic benefit of VGB is counteracted by the progressive accrual of the risk of VAVFL with continued exposure and with increase in mean dose. [source] A Combination of Midazolam and Ketamine for Procedural Sedation and Analgesia in Adult Emergency Department PatientsACADEMIC EMERGENCY MEDICINE, Issue 3 2000Carl R. Chudnofsky MD Abstract Objective: To describe the clinical characteristics of a combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department (ED) patients. Methods: This was a prospective, observational trial, conducted in the ED of an urban level II trauma center. Patients , 18 years of age requiring procedural sedation and analgesia were eligible, and enrolled patients received 0.07 mg/kg of intravenous midazolam followed by 2 mg/kg of intravenous ketamine. Vital signs were recorded at regular intervals. The adequacy of sedation, adverse effects, patient satisfaction, and time to reach discharge alertness were determined. Descriptive statistics were calculated using statistical analysis software. Results: Seventy-seven patients were enrolled. Three were excluded due to protocol violations, three due to lack of documentation, and one due to subcutaneous infiltration of ketamine, leaving 70 patients for analysis. The average age was 31 years, and 41 (59%) were female. Indications for procedural sedation and analgesia included abscess incision and drainage (66%), fracture/joint reduction (26%), and other (8%). The mean dose of midazolam was 5.6 ± 1.4 mg and the mean dose of ketamine was 159 ± 42 mg. The mean time to achieve discharge criteria was 64 ± 24 minutes. Fivepatients experienced mild emergence reactions, but there were no episodes of hallucinations, delirium, or other serious emergence reactions. Eighteen (25%) patients recalled dreaming while sedated; twelve (17%) were described as pleasant, two (3%) unpleasant, three (4%) both pleasant and unpleasant, and one (1%) neither pleasant nor unpleasant. There were four (6%) cases of respiratory compromise, two (3%) episodes of emesis, and one (1%) case of myoclonia. All of these were transient and did not result in a change in the patient's disposition. Only one (1%) patient indicated that she was not satisfied with the sedation regimen. Conclusions: The combination of midazolam and ketamine provides effective procedural sedation and analgesia in adult ED patients, and appears to be safe. [source] Evaluation of pharmacokinetics, efficacy and safety of Immunate® solvent detergent in previously treated patients with severe haemophilia AHAEMOPHILIA, Issue 1 2007L. NEMES Summary., Immunate® Solvent Detergent (S/D) is a plasma derived, purified, human factor VIII (FVIII) , von Willebrand factor (VWF) complex subjected to two virus inactivation/removal processes: S/D and vapor heat treatment. This prospective, multicentre, three-part clinical study evaluated the pharmacokinetics (in comparison to the predecessor product Immunate®), efficacy and safety of Immunate® S/D in 56 previously treated patients with severe haemophilia A. Subjects received Immunate® S/D on-demand, as a prophylactic regimen or both. The results of the pharmacokinetic population demonstrate that Immunate® and Immunate® S/D were equivalent with respect to the FVIII , and to the retrospectively VWF , parameters assessed. A total of 623 bleeding episodes were reported in 47/56 subjects. The duration of prophylaxis ranged from 0.1--5.2 months with a total of 175.6 months. The median number of bleeds per month in subjects on prophylaxis was 0 (range 0--10). Ninety-six percent of bleeding episodes were rated as having an excellent or good response. For most bleeding episodes (89%), subjects required only one infusion with a mean dose of 29.6 IU kg,1. No FVIII inhibitory antibodies were observed in any subject. No related serious adverse events were reported. Thus, the introduction of S/D treatment did not alter the PK characteristics and function of VWF and FVIII molecules of Immunate® S/D which is effective and safe for treatment of bleeding episodes, management of surgical procedures, and prophylaxis. [source] Safety and efficacy of a new recombinant FVIII formulated with sucrose (rFVIII,FS) in patients with haemophilia A: a long-term, multicentre clinical study in JapanHAEMOPHILIA, Issue 3 2001A. Yoshioka The recombinant full-length FVIII product Kogenate® has been reformulated using sucrose (rFVIII,FS) instead of human serum albumin as a stabiliser in purification and formulation. The in vivo recovery, haemostatic efficacy, and safety of rFVIII,FS were investigated in 20 previously treated patients with severe or moderate haemophilia A for , 24 weeks. In vivo recoveries of 73.5 ± 16.3%, 78.4 ± 16.1%, and 82.8 ± 23.9% after the initial infusion of 50 IU kg,1 rFVIII,FS and at weeks 12 and 24, respectively, showed no significant changes over time. A total of 1115 infusions (mean dose 24.1 ± 8.4 IU kg,1) were included in the analysis of haemostatic efficacy. One (80.5%) or two (8.2%) infusions achieved adequate haemostasis in 88.7% of all bleeding episodes, and haemostatic efficacy was judged ,excellent' or ,good' in 749 of 764 episodes (98.0%). The haemostatic efficacy was judged as ,excellent' or ,good' in 924 of 1115 (82.9%) infusions. Twenty-one adverse events were observed in 12 patients in the total 1541 infusions included in the safety analysis. Causality with respect to rFVIII,FS could not be ruled out in three events in one HIV-negative patient: elevated CD4(%), decreased CD8(%), and elevated CD4/CD8 ratio. No FVIII inhibitor development was observed in any patient. ELISA assay testing for antibodies to rFVIII, baby hamster kidney cell (BHK) protein, and murine IgG were all negative. These results show that rFVIII,FS is a safe and effective for long-term treatment of patients with haemophilia A. [source] Postoperative brachytherapy alone and combined postoperative radiotherapy and brachytherapy boost for squamous cell carcinoma of the oral cavity, with positive or close margins,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2004Michel Lapeyre MD Abstract Background. Postoperative radiotherapy is necessary for squamous cell carcinoma (SCC) of the oral cavity with positive or close margins. The aim of the study is to define the indications of postoperative brachytherapy (BRT). Methods. From 1979 to 1993, 82 patients with positive or close margins had postoperative BRT (58 T1,2, 24 T3,4, 45 mobile tongue, 37 floor of mouth). Forty-six patients had combined radiotherapy (RT) with a mean dose of 48 Gy, and BRT boost with a mean dose of 24 Gy. Thirty-six patients had BRT alone with a mean dose of 60 Gy. BRT was performed with interstitial low dose rate Iridium 192. Results. Overall survival (OS), cause-specific survival (CSS), and local control (LC) at 5 years were, respectively, for T1,2/N0N, with BRT, 75%, 85%, and 88%,and with RT-BRT 70%, 92%, and 92%; for T1,2/N+ with RT-BRT, 44%, 67%, and 78%; for T3,4/N, with RT-BRT, 42%, 90%, and 80%; and for T3,4/N+ with RT-BRT, 22%, 43%, and 57%. Prognostic factors for OS, CSS, and LC were N+ (p , .009), extracapsular spread (ECS+;p , .000001), and T stage for LC only (p = .02). Prognostic factors for complications were a high number of wires with a cutoff at five wires (p = .008), a high dose rate with a cutoff at 0.57 Gy/hr (p = .01), and a high total dose (BRT + RT) with a cutoff at 71 Gy (p = .07). Conclusions. BRT alone for SCC T1,2/N0N, is better than RT-BRT because, with equivalent results, it avoids the adverse events of postoperative RT (xerostomia) and permits the treatment of a second head and neck primary in nonirradiated tissue. The results for the T3,4/N, are acceptable with this approach (ie, RT-BRT) but may be improved for N+. © 2004 Wiley Periodicals, Inc. Head Neck26: 216,223, 2004 [source] High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C,HEPATOLOGY, Issue 2 2005Karin Lindahl Improved treatment regimens for patients with chronic hepatitis C, genotype 1 and high viral load are needed. Increasing the dose of ribavirin has increased the response rate, but experience with doses of more than 1,200 mg/day is limited. The aim of this study was to investigate the safety and tolerance to treatment with a high and individualized dose of ribavirin in combination with peginterferon. Ten patients with chronic hepatitis C, genotype 1 and high viral load were treated with peginterferon alfa-2a and ribavirin for 48 weeks in a prospective trial. The initial ribavirin dose was individualized and calculated from a pharmacokinetic formula based mainly on renal function. Ribavirin plasma concentrations were monitored, and the dose was adjusted to reach the target concentration. Hemoglobin was monitored, and patients were treated with erythropoietin and blood transfusions when indicated. After dose adjustments, the mean dose of ribavirin was 2,540 mg/day (range, 1,600-3,600) at week 24. The main side effect was anemia, which was controlled with erythropoietin. Two patients required blood transfusions. One patient was withdrawn at week 24 because of a lack of viral response, and one patient at week 39 because of side effects, primarily interferon associated. At follow-up (,24 weeks posttreatment), nine of ten patients had undetectable HCV RNA and thus were cured by standard definitions. In conclusion, a high dose of ribavirin according to an individualized schedule is feasible but associated with more frequent and serious side effects such as anemia. The viral response merits further evaluation. (HEPATOLOGY 2005;41:275,279.) [source] Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2006Pinkhas Sirota Abstract Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637,mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16,mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (,7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia. Copyright © 2006 John Wiley & Sons, Ltd. [source] One-year treatment of Alzheimer's disease with acetylcholinesterase inhibitors: improvement on ADAS-cog and TMT A, no change or worsening on other testsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2005Alina Borkowska Abstract The aim of this study was to assess cognitive functioning measured by selected psychometric and neuropsychological tools in patients with Alzheimer's disease (AD) after 1-year treatment with acetylcholinesterase inhibitors. Seventy-six patients (22 male and 54 female) with a mild to moderate stage of AD, aged 56,86 (mean 68) years, were treated. Forty-seven received donepezil (mean dose 9.3,mg/d) and 29 rivastigmine (mean dose 8.5,mg/d). Cognitive measurements included: the mini mental state examination (MMSE), the Alzheimer disease assessment scale-cognitive (ADAS- cog), the trail making test (TMT) and the Stroop color word interference test. The assessments were made before and after 3, 6 and 12 months of treatment. A significant improvement in ADAS-cog (p,<,0.001, 83% of patients improved) and a worsening in MMSE (84% of patients worsened, p,<,0.01 after 6 and 12 months) was noted after the 1 year treatment. A majority of patients (57%) improved in the TMT-A (p,<,0.001), measuring psychomotor speed and worsened in the TMT-B (p,<,0.01, after 12 months), and Stroop B test (p,<,0.001), measuring working memory and executive functions, 53% and 61%, respectively. Most patients (83%) did not change their performance in the Stroop A (improvement after 3 months, p,<,0.001, worsening after 6 and 12 months p,<,0.01) test measuring verbal abilities, after 1 year treatment. The results obtained suggest that the treatment with cholinergic drugs may improve global cognitive functioning (ADAS-cog) and psychomotor speed (TMT A), however, such treatment is unable to prevent the deterioration of working memory and executive functions. Copyright © 2005 John Wiley & Sons, Ltd. [source] Appropriate dosing of antiarrhythmic drugs in Japan requires therapeutic drug monitoring,JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2005M. Takada PhD Summary Objective:, In general, drugs are used in accordance with an approved dosage regimen in expectation of an appropriate balance between efficacy and toxicity. However, dose control of drugs with a narrow therapeutic range and marked intersubject variability in pharmacokinetics should be established through individualization of dosing based on therapeutic drug monitoring (TDM). The purpose of this study was to examine differences between the approved dosage regimen and the doses of antiarrhythmic drugs and digoxin used in clinical practice and to examine the influence of TDM on dosing. Methods:, Prescription research of antiarrhythmic drugs was performed at five national hospitals in Japan. Prescriptions for antiarrhythmic drugs (cibenzoline, disopyramide, pirmenol, mexiletine, aprindine, flecainide, pilsicainide, amiodarone and digoxin) were counted for the study period. The mean dose and dose distribution of the drugs were determined in each hospital. Comparisons were made of mean dose obtained in the study with the dosage approved by the authority. In addition, the percentage of patients that received TDM was determined. Results:, A difference was seen between the approved dosage and the actual dose. For all drugs except flecainide, the mean dose was smaller than the approved dosage. For all drugs except digoxin, remarkable variations were seen in the dose distribution among the hospitals. Digoxin showed a similar dose distribution among the five hospitals. Overall, the percentage of patients that received TDM was low except for Hospital A. However, TDM of digoxin was relatively common at four of the hospitals. Conclusions:, It is concluded that, with the exception of digoxin, the appropriate dosing regimen for antiarrhythmic drugs is not yet established. The establishment of appropriate dosing regimens for antiarrhythmic drugs requires the more widespread adoption of TDM. [source] ORIGINAL ARTICLE: Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: A dosimetric study using helical tomotherapyJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 4 2010JC Marsh Abstract Introduction:, The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). Methods and Materials:, We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch = 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with V100 , 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V100. Results:, In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean V100 for the rest of the brain (PTV) were 94.7% (PCI) and 95.1% (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27,17.5). Conclusions:, It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose. [source] Dosimetric comparison of intensity modulated radiotherapy techniques and standard wedged tangents for whole breast radiotherapy*JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 1 2009Andrew Fong Summary Prior to introducing intensity modulated radiotherapy (IMRT) for whole breast radiotherapy (WBRT) into our department we undertook a comparison of the dose parameters of several IMRT techniques and standard wedged tangents (SWT). Our aim was to improve the dose distribution to the breast and to decrease the dose to organs at risk (OAR): heart, lung and contralateral breast (Contra Br). Treatment plans for 20 women (10 right-sided and 10 left-sided) previously treated with SWT for WBRT were used to compare (a) SWT; (b) electronic compensators IMRT (E-IMRT); (c) tangential beam IMRT (T-IMRT); (d) coplanar multi-field IMRT (CP-IMRT); and (e) non-coplanar multi-field IMRT (NCP-IMRT). Plans for the breast were compared for (i) dose homogeneity (DH); (ii) conformity index (CI); (iii) mean dose; (iv) maximum dose; (v) minimum dose; and dose to OAR were calculated (vi) heart; (vii) lung and (viii) Contra Br. Compared with SWT, all plans except CP-IMRT gave improvement in at least two of the seven parameters evaluated. T-IMRT and NCP-IMRT resulted in significant improvement in all parameters except DH and both gave significant reduction in doses to OAR. As on initial evaluation NCP-IMRT is likely to be too time consuming to introduce on a large scale, T-IMRT is the preferred technique for WBRT for use in our department. [source] Population pharmacokinetics of pyrazinamide in elephantsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2005M. ZHU This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty-three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20,30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0,24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with Tmax at or before 2 h regardless of the method of drug administration. Cmax at a mean dose of 25.6 (±4.6) mg/kg was 19.6 (±9.5 ,g/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 ± 4.2 mg/kg, Cmax was 25% (4.87 ± 4.89 ,g/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 ± 15.2 mg/kg yielded Cmax of 12.3 ± 6.3 ,g/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher Cmax and lower inter-subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between 1 and 2 h postdose. Higher doses may be required if the achieved Cmax values are below the recommended 20,50 ,g/mL range. [source] Double-blind study of pardoprunox, a new partial dopamine agonist, in early Parkinson's disease,MOVEMENT DISORDERS, Issue 6 2010Juliana Bronzova MD Abstract This study examined the efficacy and safety of the partial dopamine agonist, pardoprunox (SLV308), in the treatment of patients with early Parkinson's disease (PD). Patients were randomized to receive pardoprunox (n = 69) or placebo (n = 70). Pardoprunox was titrated to each patient's optimal dose (9,45 mg/d) over 2 to 6 weeks and then maintained at this dose for a further 3 weeks. Concomitant anti-Parkinson treatment was not permitted. In the primary analysis, Unified PD Rating Scale (UPDRS)-Motor score was improved in pardoprunox-treated patients (overall mean dose 23.8 mg/d; ,7.3 points), as compared with placebo (,3.0 points; P = 0.0001), from baseline to end point. At end point, there were more responders (,30% reduction in UPDRS-Motor score) in the pardoprunox group (50.7%) than in the placebo group (15.7%; P < 0.0001). In other secondary analyses, UPDRS-activities of daily living (ADL) and -ADL+Motor scores were also significantly more improved in the pardoprunox group. Nausea was reported by 32 of 68 (47.1%) pardoprunox-treated patients (vs. 3/70, 4.3%, placebo-treated patients), with dizziness, somnolence, headache, and asthenia also reported by ,10 patients. In this exploratory proof-of-concept study, pardoprunox significantly improved motor function in patients with early PD. The efficacy and safety profile of pardoprunox justifies its further investigation in PD. © 2010 Movement Disorder Society [source] Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay,MOVEMENT DISORDERS, Issue 10 2008Mitchell F. Brin MD Abstract To evaluate the immunogenicity of botulinum toxin type A (BoNTA; BOTOX) in cervical dystonia (CD). Subjects diagnosed with CD for ,1 year and previously naďve to BoNTs were treated with BoNTA in a prospective, open-label, multicenter study. Serum samples were analyzed for BoNTA neutralizing antibodies using the Mouse Protection Assay (MPA). Clinical resistance was assessed with a test injection of 20 U BoNTA placed unilaterally into the frontalis (Frontalis Antibody Test; FTAT) or corrugator muscle (Unilateral Brow Injection; UBI). Efficacy was assessed and adverse events were recorded. Of 326 subjects enrolled, 251 (77%) completed the study. Subjects received a median of 9 BoNTA treatments (mean dose per session ranged from 148.4 to 213.0 U over a mean of 2.5 years [range: 3.2 months,4.2 years]). Only 4 of 326 subjects (1.2%) tested positive for antibodies in the MPA; three of these subjects stopped responding clinically to BoNTA (of whom one also showed clinical resistance in the FTAT) and one continued to respond. Consistent improvements in the signs/symptoms of CD were noted. The most frequent treatment-related adverse events were mild to moderate weakness, dysphagia, neck pain, and injection-site pain. The current formulation of BoNTA rarely causes neutralizing antibody formation in CD subjects treated ,4 years. © 2008 Movement Disorder Society [source] Olanzapine treatment for dopaminergic-induced hallucinationsMOVEMENT DISORDERS, Issue 5 2002William G. Ondo MD Abstract Atypical antipsychotic medications with lower affinities for D2 receptors are considered useful alternatives to treat drug-induced hallucinations in Parkinson's disease (PD). We conducted a double-blind, placebo-controlled, unforced titration, parallel design study (2:1 drug to placebo randomization ratio) using olanzapine (2.5,10 mg/day to effect) in 30 PD patients with drug-induced hallucinations. We performed an extensive battery of neuropsychological tests, the Unified Parkinson's Disease Rating Scale (UPDRS), assessments of on and off time at baseline and at 9 weeks after starting the medication. Sixteen patients on olanzapine (mean dose, 4.6 mg/night) and 11 on placebo completed the study. Compared with placebo, performance on the UPDRS item 2 (thought disorder), and a structured interview for hallucinations, both tended to improve on drug but neither reached statistical significance. A neuropsychological test battery did not show any significant differences. Total on UPDRS motor scores (P < 0.05) and timed tapping (P < 0.01) worsened while on drug compared to placebo. Bradykinesia (P < 0.01) and gait (P < 0.001) items on the UPDRS largely accounted for this deterioration. After completion of the study, 8 of 16 patients randomly assigned to drug continued olanzapine at a mean dose of 2.4 mg/day. However, at the last recorded visit only 5 of 24 (20.8%) of all patients exposed to drug (including those originally randomly assigned to placebo) remained on olanzapine. In patients with PD, low-dose olanzapine did not significantly improve hallucinations but did worsen motor function. © 2002 Movement Disorder Society [source] Midazolam as a sole sedative for computed tomography imaging in pediatric patientsPEDIATRIC ANESTHESIA, Issue 9 2009RANJU SINGH MD Summary Objective:, To evaluate the efficacy and adverse effects of i.v. midazolam as a sole agent for sedation in children for computed tomography (CT) imaging. Materials and Methods:, Prospective clinical trial in which 516 children under ASA classification II,IV (273 boys and 243 girls) in the age group of 6 months to 6 years for elective CT scan were enrolled over a 17-month period. Patients were administered i.v. midazolam 0.2 mg·kg,1 and further boluses of 0.1 mg·kg,1 (total 0.5 mg·kg,1) if required. Measurements included induction time, efficacy, side effects, complications, and degree of sedation. Sedation was graded on the basis of Ramsay sedation score (RSS) as over sedated (RSS 5,6), adequately sedated (AS, RSS 3,4), under sedated (RSS 1,2), or failed if the procedure could not be completed or another agent had to be administered. Results:, Of the 516 procedures, 483 brains, 16 chests, and 17 abdomens were scanned with a mean duration of 4.75 ± 1.75 min with a mean dose of 0.212 mg·kg,1 of i.v. midazolam. Four hundred and sixty-five (90.12%) patients were AS in 5.9 ± 0.7 min while 40 (7.75%) patients required additional boluses. Of these 40 patients, 24 (4.65%) required a single bolus, 12 (2.32%) required two boluses, whereas the remaining four (0.78%) required three boluses. In 11 (2.13%; P < 0.0001) patients, the scan could not be completed satisfactorily. Side effects were seen in 46 (9.11%) patients in the form of desaturation, hiccups (seven patients, 1.38%), and agitation (four patients, 0.79%). Desaturation (SpO2 90,95%) was seen in 35 (6.93%) patients, which was corrected by topical application of oxygen. None of the patients exhibited any complications such as pulmonary aspiration or need to maintain airway. The patients were kept under observation for 1 h after the procedure. Conclusion:, The level of sedation achieved in children with midazolam 0.2 mg·kg,1 is adequate for imaging with minimal side effects, no airway complications, and fast recovery. It can be recommended as the sole agent for sedation in pediatric patients for CT imaging. [source] Tiagabine in treatment refractory bipolar disorder: a clinical case seriesBIPOLAR DISORDERS, Issue 5 2002Trisha Suppes Objectives:, Anticonvulsants have provided major treatment advances for patients with bipolar disorder. Many of these drugs, including several with proven efficacy in bipolar mania or depression, enhance the activity of the ,-amino butyric acid (GABA) neurotransmitter system. A new anticonvulsant, tiagabine, has selective GABAergic activity and is approved for patients with partial epilepsy. Few reports of its potential effectiveness in bipolar disorder, however, have been published. We sought to evaluate the effectiveness of tiagabine added to ongoing medication regimens in patients with bipolar disorder inadequately responsive to or intolerant of usual treatments. Methods:, Seventeen treatment-refractory patients participating in the Stanley Foundation Bipolar Network (SFBN) long-term follow-up study were offered open treatment with add-on tiagabine after discussion of the risks, benefits, other treatment options and giving informed consent. Patients' clinical symptoms and somatic complaints were closely monitored with SFBN longitudinal and cross-sectional ratings. Four patients discontinued low-dose tiagabine prior to the second visit and were excluded from data analysis. Results:, Thirteen patients received a mean of 38 days of treatment at a mean dose of 8.7 mg/day of tiagabine. On the Clinical Global Impression Scale for Bipolar Disorder Overall category, three (23%) patients showed much or very much improvement and 10 (77%) patients showed no change or worsening. Three significant adverse events were noted, including two presumptive seizures. Conclusions:, Open add-on tiagabine for treatment-refractory patients with bipolar disorder demonstrated limited efficacy with the majority of patients showing no change or worsening of clinical symptoms. In addition, patients experienced serious side-effects attributed as likely due to the medication, which resolved without lasting consequence when tiagabine was discontinued. [source] Comparative efficacy of two ,1 -adrenoreceptor antagonists, doxazosin and alfuzosin, in patients with lower urinary tract symptoms from benign prostatic enlargementBJU INTERNATIONAL, Issue 6 2004T.M. De Reijke OBJECTIVES To compare doxazosin and alfuzosin in patients with moderate to severe lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction. PATIENTS AND METHODS In all, 210 men with LUTS were randomized to receive doxazosin 1,8 mg once daily or alfuzosin 5,10 mg divided in two or three daily doses in a 14-week, multicentre, double-blind, baseline-controlled, dose-titration study. The International Prostate Symptom Score (IPSS) and maximum urinary flow rate were used to assess the efficacy of the treatment. RESULTS At study completion, the mean dose of doxazosin was 6.1 mg/day and alfuzosin 8.8 mg/day. The least squares mean (se) change from baseline in total IPSS was ,9.23 (0.6) for doxazosin and ,7.45 (0.6) (both P < 0.001) for alfuzosin. The respective mean change from baseline in irritative symptoms was ,3.5 (0.2) and ,2.8 (0.3) (both P < 0.001). The differences between the treatment groups were statistically significant in favour of doxazosin (total IPSS, P = 0.036; irritative symptoms, P = 0.049). The improvement between groups was also significantly different for postvoid residual urine volume, at ,29.19 (8.6) and +,9.59 (8.9) mL for doxazosin and alfuzosin, respectively (P = 0.002). Improvements in mean and maximum urinary flow rates were similar for both treatments, at +,1.5 and +,1.2, and +,2.8 and +,2.5 mL/s, respectively. Doxazosin and alfuzosin were both well tolerated, with most all-cause adverse events reported as mild or moderate. CONCLUSIONS The mean doses of doxazosin and alfuzosin used in this study were not equipotent. Doxazosin 6.1 mg/day produced significantly greater improvements than alfuzosin 8.8 mg/day in total and irritative urinary symptom scores and postvoid residual urine volume in men with moderate to severe LUTS. Changes in maximum and mean flow rates were comparable. Doxazosin and alfuzosin were both well tolerated. [source] Influence of methotrexate exposure on outcome in patients treated with MBVP chemotherapy for primary central nervous system lymphomaBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2010Hélčne Blasco WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Although treated using the same high-dose methotrexate (HD-MTX)-based multiagent chemotherapy, patients with primary central nervous system lymphoma (PCNSL) have significant differences in outcome. However, little information has been published about factors influencing outcome in PCNSL. As it is known that the pharmacokinetics of MTX vary considerably between subjects leading to different exposure in patients receiving the same dose, it is important to evaluate its role in response to chemotherapy. WHAT THIS STUDY ADDS This study is the first to evaluate the exposure,response relationship in patients treated with MBVP chemotherapy. We found that patients who were early non-responders to MBVP chemotherapy had poor survival, whatever the salvage regimen. Tumour response at early evaluation was not associated with MTX pharmacokinetics and increasing the dose would probably not improve results. AIMS Although the standard treatment for primary central nervous system lymphoma (PCNSL) consists of three cycles of MBVP (methotrexate, BCNU, VP16, methylprednisolone) and radiotherapy, early failure of treatment may require modification of the treatment. However, our understanding of the outcome in such patients and of the factors involved in early failure of treatment is poor. In addition to known prognostic factors, we evaluated the influence of methotrexate (MTX) exposure on the response to MBVP chemotherapy in patients treated for PCNSL after the first two cycles. METHODS We retrospectively analyzed all patients with PCNSL treated with the MBVP regimen over the previous 10 years. Clinical, personal data and known prognostic factors were studied. The parameters of MTX exposure were estimated using a population pharmacokinetic approach with NONMEM. Objective response (OR), overall survival (OS) and failure-free survival (FFS) were evaluated in all patients. RESULTS Thirty-seven patients were studied. We observed lower FFS and OS (0.49 years) in patients who were not able to receive the planned treatment (group 1, n= 12) than in those who received three cycles (8.04 years) (group 2, n= 25). Known prognostic factors were comparable in both groups, but mean dose of MTX and mean AUC tended to be lower in patients who failed prematurely or showed no response after two cycles. CONCLUSIONS We found that patients who were early non-responders to MBVP chemotherapy had poor survival, without major influence of MTX exposure. It is thus probably unlikely that increasing the dose of MTX would improve outcome. [source] Neurocognitive function in patients with small cell lung cancer,CANCER, Issue 3 2008Effect of prophylactic cranial irradiation Abstract BACKGROUND. The use of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) has been tempered by fears of detrimental effects on cognitive function. Neuropsychologic testing was prospectively conducted before and after PCI to evaluate its effects on cognitive function in patients with SCLC. METHODS. Ninety-six patients who completely or partially responded to initial therapy underwent formal neurocognitive testing before PCI. Three patients who had central nervous system metastasis were excluded. Of the remaining patients, 69 received PCI (mean dose, 25 grays [Gy] in 10 fractions). Repeat testing was performed on 37 patients (median follow-up, 23 months; range, 6,120 months). RESULTS. Baseline impairment was defined as ,1.5 standard deviations below the normative mean. Before undergoing PCI, 47% of patients had evidence of impaired cognitive function. After PCI, univariate analysis revealed significant transient declines in executive function (pre-PCI mean, 15.6 ± 11.5; post-PCI, 27.1 ± 17.6 [P = .008]) and language (pre-PCI mean, 33.8 ± 9.9; post-PCI, 31.0 ± 9.0 [P = .049]) at early timepoints. Controlling for noncentral nervous system disease progression the deficit in executive function was no longer significant. Moreover, these deficits were not sustained, and significant improvements in language and motor coordination were recorded. On multivariate analysis, no significant differences before and after PCI were found. CONCLUSIONS. Neurocognitive testing demonstrated that a substantial portion of patients with SCLC had impaired brain functioning at baseline. Persistent declines in cognitive function were not observed after cranial irradiation. These data do not favor the omission of PCI on the basis of fears of neurotoxic effects. Cancer 2008. © 2007 American Cancer Society. [source] Rapid titration with intravenous morphine for severe cancer pain and immediate oral conversionCANCER, Issue 1 2002Sebastiano Mercadante M.D. Abstract BACKGROUND Cancer pain emergencies presenting with severe excruciating pain require a rapid application of powerful analgesic strategies. The aim of the current study was to evaluate a method of rapid titration with intravenous morphine to achieve relief of cancer pain of severe intensity. METHODS Forty-nine consecutive patients admitted to a Pain Relief and Palliative Care Unit for severe and prolonged pain were enrolled in the study. Pain was evaluated on a numeric scale of 0,10 (0 indicated no pain and 10 indicated excruciating pain). After the initial assessment (T0), an intravenous line was inserted and boluses of morphine (2 mg every 2 minutes) were given until the initial signs of significant analgesia were detected or severe adverse effects occurred (T1). A continuous reassessment was warranted and the effective total dose administrated intravenously was assumed to last approximately 4 hours and was calculated for 24 hours. The dose immediately was converted to oral morphine (a 1:3 ratio for low doses and a 1:2 ratio for high doses). RESULTS Data from 45 patients was analyzed. A significant decrease in pain intensity was achieved in a mean of 9.7 minutes (95% confidence interval [95% CI], 7.4,12.1 minutes), using a mean dose of intravenous morphine of 8.5 mg (95% CI, 6.5,10.5 mg). The doses administered rapidly were converted to oral morphine and pain control was mantained until the patient's discharge, which occurred in a mean of 4.6 days (95% CI, 4.1,5.2 days). The incidence of adverse effects was minimal. CONCLUSIONS The results of the current study demonstrate that cancer pain emergencies can be treated rapidly in the majority of cancer patients with an acceptable level of adverse effects. Intravenous administration of morphine requires initial close supervision and continuity of medical and nursing care. Cancer 2002;95:203,8. © 2002 American Cancer Society. DOI 10.1002/cncr.10636 [source] Isosorbide dinitrate inhibits platelet adhesion and aggregation in nonthrombolyzed patients with acute myocardial infarctionCLINICAL CARDIOLOGY, Issue 11 2000Jadwiga Gebalska M.D., Ph.D. Abstract Background: Apart from their vasodilatator properties, nitrates have been shown to inhibit platelet aggregation. The effects of nitrates on platelet adhesion have not been studied. Nonselected patients with acute myocardial infarction (AMI) have been suggested to gain no benefit from administration of nitrates. However, the importance of nitrates may be greater in a subgroup of nonthrombolyzed patients with AMI. Hypothesis: Isosorbide dinitrate (ISDN) decreases platelet adhesion and aggregation in nonthrombolyzed patients with AMI. Methods: Consecutive 48 men with AMI, not eligible for thrombolytic therapy because of late presentation (> 12 h), were prospectively randomized 2:1 to double-blind ISDN (mean dose 2.4 ± 0.9 mg/h) (n = 33) or placebo (0.9% sodium chloride) (n = 15) infusion. All patients received aspirin. Blood samples were taken at baseline (no study medication) and 3 h into ISDN or placebo infusion. Platelet adhesion to collagen was measured in the ethylene diamine tetraacetic acid (EDTA)-platelet rich plasma by recording changes in light transmission with an optical aggregometer. Platelet aggregation was measured using the Born's method. Results: Isosorbide dinitrate significantly decreased both platelet adhesion and aggregation. No effect was seen in the placebo group. Conclusions: In patients with AMI who do not receive thrombolytic therapy, ISDN effectively inhibits platelet adhesion and aggregation. These effects of nitrates may be of therapeutic and prognostic significance in this group of patients. [source] Assessment of quality of life in adults receiving long-term growth hormone replacement compared to control subjectsCLINICAL ENDOCRINOLOGY, Issue 1 2003I. A. Malik Summary objective There are few studies of quality of life (QOL) in adults with growth hormone deficiency (GHD) compared to matched control populations without GHD. These have shown impairments in a variety of QOL measures, which improve but do not normalize after short-term replacement with GH. There is little information on QOL in long-term treated GHD patients compared with controls without GHD. patients and methods A total of 120 adults with GHD who had received GH replacement for at least 1 year were identified from the neuroendocrine clinic. Patients were asked to complete eight QOL questionnaires and an Energy Visual Analogue Scale (VAS). Results were compared with 83 control subjects without GHD from the local population who agreed to complete seven of the QOL questionnaires (excluding Disease Impact scale) and the energy VAS. The eight questionnaires were a combination of generic and disease-specific questionnaires used to assess health related QOL, namely: Short Form-36 (SF-36), Nottingham Health Profile (NHP), Disease Impact, Life Fulfilment and Satisfaction scales, Mental Fatigue Questionnaire (MFQ) and Self Esteem scale, Hospital Anxiety Depression (HAD) scale and QOL-AGHDA (assessment of GHD in adults). results Eighty-nine patients returned questionnaires and 85 (71%) had complete data for analysis. The mean (SD) duration of GH replacement was 36·0 ± 26·4 (range 13,159) months. Mean age was 43·9 ± 15·8 years (37 males) in treated GHD patients compared to a mean age 41·7 ± 10·5 years (32 males) in the controls. Mean IGF-1 levels were 22·5 ± 13·6 nmol/l in the GHD patients and the mean dose of GH replacement was 1·2 ± 0·4 IU daily. Analysis of the QOL questionnaires from the GH treated patients revealed highly significant impairments in all measures (most P , 0·0001, except life fulfilment-material, P = 0·33) compared to the control population. conclusions This large population with treated GH deficiency have significant impairments in multiple aspects of QOL despite replacement with GH and other pituitary hormones for at least 1 year (mean 3 years). It is likely therefore that other factors in addition to GH deficiency must influence QOL in these patients. Further strategies to improve QOL in these individuals should therefore be considered, e.g. psychological support and treatments and physical treatments (such as exercise programmes). [source] Multiple doses of secretin in the treatment of autism: a controlled studyACTA PAEDIATRICA, Issue 5 2002E Sponheim Dramatic effects on autistic behaviour after repeated injections of the gastrointestinal hormone secretin have been referred in a number of case reports. In the absence of curative and effective treatments for this disabling condition, this information has created new hope among parents. Although controlled studies on the effect of mainly one single dose have not documented any effect, many children still continue to receive secretin. Six children enrolled in a double-blind, placebo-controlled crossover study in which each child was its own control. Human synthetic secretin, mean dose 3.4 clinical units, and placebo were administered intravenously in randomized order every 4th wk, on three occasions each. The measurement instruments were the visual analogue scale (VAS) and the aberrant behaviour checklist (ABC). Statistically significant differences were found for placebo in 3 out of 6 children and for secretin in one child, using parental ratings only (VAS scores). Differences were small and lacked clinical significance, which was in accordance with the overall impression of the parents and teachers and visual inspection of graphs. Conclusion: In this placebo-controlled study, multiple doses of secretin did not produce any symptomatic improvement. [source] Improved glycaemic control with metformin,glibenclamide combined tablet therapy (Glucovance®) in Type 2 diabetic patients inadequately controlled on metforminDIABETIC MEDICINE, Issue 8 2002M. Marre Abstract Aims To evaluate the efficacy and safety of two dosage strengths of a single-tablet metformin,glibenclamide (glyburide) combination, compared with the respective monotherapies, in patients with Type 2 diabetes mellitus (DM) inadequately controlled by metformin monotherapy. Methods In this 16-week, double-blind, multicentre, parallel-group trial, 411 patients were randomized to receive metformin 500 mg, glibenclamide 5 mg, metformin,glibenclamide 500 mg/2.5 mg or metformin,glibenclamide 500 mg/5 mg, titrated with the intention to achieve fasting plasma glucose (FPG) , 7 mmol/l. Results Decreases in glycated haemoglobin (HbA1c) and FPG were greater (P < 0.05) for metformin,glibenclamide 500 mg/2.5 mg (,1.20% and ,2.62 mmol/l) and 500 mg/5 mg (,0.91% and ,2.34 mmol/l), compared with metformin (,0.19% and ,0.57 mmol/l) or glibenclamide (,0.33% and ,0.73 mmol/l). HbA1c < 7% was achieved by 75% and 64% of patients receiving metformin,glibenclamide 500 mg/2.5 mg and 500 mg/5 mg, respectively, compared with 42% for glibenclamide and 38% for metformin (P = 0.001). These benefits were achieved at lower mean doses of metformin or glibenclamide with metformin,glibenclamide 500 mg/2.5 mg and 500 mg/5 mg (1225 mg/6.1 mg and 1170 mg/11.7 mg) than with glibenclamide (13.4 mg) or metformin (1660 mg). Treatment-related serious adverse events occurred in two patients receiving glibenclamide. Plasma lipid profiles were unaffected and mean changes in body weight were , 1.0 kg. Conclusions Intensive management of Type 2 DM with a new metformin,glibenclamide combination tablet improved glycaemic control and facilitated the attainment of glycaemic targets at lower doses of metformin or glibenclamide compared with the respective monotherapies, without compromising tolerability. Diabet. Med. 19, 673,680 (2002) [source] Postoperative analgesic requirements , total laparoscopic hysterectomy versus vaginal hysterectomyAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2005Marcelo Carraro NASCIMENTO Abstract Background:, There is limited information available on the requirement for postoperative analgesic drugs in patients submitted to total laparoscopic hysterectomy (TLH) compared with patients undergoing vaginal hysterectomy (VH). Aim:, To compare the postoperative analgesic requirements in patients who underwent a TLH with patients who had a VH. Methods:, Chart review of 53 patients who had TLH and 47 who had VH and were seen postoperatively by an acute pain management service in order to assess postoperative analgesic requirements. Patient controlled analgesia (PCA) was part of the standard protocol for postoperative pain management. Analgesic requirement was recorded as the mean doses of morphine and number of days that patients used non-steroidal anti-inflammatory drugs (NSAIDs), oxycodone and tramadol. Results:, The requirement for total morphine was approximately half the dose in patients who had a TLH (10.8 ± 12.6 mg) compared with patients who had a VH (19.4 ± 21.9 mg) (P 0.017). The length of use of NSAIDs was significantly reduced in patients who had undergone a TLH (2.0 ± 0.95 days) as compared with patients who had a VH (2.85 ± 1.1 days) (P < 0.0001). Conclusions:, Patients submitted to TLH require less postoperative analgesic drugs when compared with patients who had VH. Prospective randomised trials are warranted to compare analgesic requirements between patients submitted to TLH and VH. [source] | ||||||||||||||||||||||||||||