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Study Endpoint (study + endpoint)
Selected AbstractsSalvage treatment for recurrent oropharyngeal squamous cell carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2010Christof Röösli MD Abstract Background. This study evaluates the oncological outcome of patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after primary radiation therapy ± chemotherapy, primary surgical therapy, and surgical therapy followed by radiation therapy ± chemotherapy. Methods. A total of 156 patients (36%) of a cohort of 427 treated for OPSCC between 1990 and 2006 developed recurrent disease. Fifty-one patients (12%) qualified for salvage treatment. Study endpoints were 5-year overall survival (OS) and disease-specific survival (DSS). Results. The 5-year OS and DSS rates after salvage treatment were 29% and 40%; after initial primary radiation therapy, 25% and 40%; after initial surgery followed by radiation therapy, 40% and 40%; and after initial surgery alone, 20% and 40%. Conclusions. Patients with an advanced OPSCC have a considerable risk for recurrence. Despite poor ultimate outcome, salvage treatment should be attempted in patients with resectable disease, good performance status, and absence of distant metastases. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] The Role of Intra-Aortic Counterpulsation in High-Risk OPCAB Surgery:JOURNAL OF CARDIAC SURGERY, Issue 4 2003A Prospective Randomized Study This prospective and randomized study evaluates the efficacy and safety of pre- and perioperative IABC in high-risk OPCAB. Material: Group A,IABC started prior to induction of anesthesia (n = 15); group B,no preoperative IABC (n = 15). Adult high-risk coronary patients to undergo OPCAB. High risk = (minimum 2) EF < 0.30, left main stenosis, unstable angina, redo. Bailout if hemodynamic instability CPB or IABC in group B. Study endpoints (a) cardiac protection (troponin 1, cardiac index (CI), ECG), (b) inflammatory response (lactate, IL-6), (c) clinical outcome (mortality, morbidity). Emergency operations 33%, re-operation 13%, unstable angina 100%, left main 60% and EF 0.29, without group differences. Results: No bailout group A, 10 in group B, p < 0.0001. Postoperative IABC six (group A) and seven patients (group B), during 6.8 ± 5.1 hours (group A) versus 41.2 ± 25.5 hours (group B), p = 0.0110. Myocardial protection without group differences, but CI significantly better in group A. Inflammatory response significantly less in group A. Clinical outcomes: one death, one MI and two renal failure in group B, none in group A. Intensive care unit (ICU) stay 27 ± 3 hours (group A) versus 65 ± 28 hours (group B), p = 0.0017. LOS 8 ± 2 days (group A) versus 15 ± 10 (group B), p = 0.0351. No IABC related complications. Conclusions: Pre- and perioperative IABC therapy offers efficient hemodynamic support during high-risk OPCAB surgery, lowers the risk of hemodynamic instability, is safe and shortens both ICU and hospital length of stay significantly, and is a cost-effective therapy. (J Card Surg 2003; 18:286-294) [source] Idiopathic thrombocytopenic purpura in childhood: Controversies and solutionsPEDIATRIC BLOOD & CANCER, Issue S5 2006Thomas Kühne MD Abstract Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder in patients who are otherwise healthy and present with thrombocytopenia with normal red cells and leukocytes. ITP is a diagnosis of exclusion and is in origin heterogeneous. The unknown etiology and the lack of clinical data from controlled prospective studies are reasons for controversies in diagnosis and management. Study endpoints traditionally include the velocity of platelet increase after drug intervention or observation, although a rapid elevation of the platelet count is of questionable clinical value. Evaluation of other endpoints is needed. Pediatr Blood Cancer 2006;47:650,652. © 2006 Wiley-Liss, Inc. [source] From Adjuvant Therapy to Breast Cancer Prevention: BCPT and STARTHE BREAST JOURNAL, Issue 3 2001Barbara K. Dunn MD Abstract: The continued widespread prevalence of breast cancer supports placing a high priority on research aimed at its primary prevention, particularly among women who are at increased risk for developing this disease. The suggestion of potential agents for the primary chemoprevention of breast cancer evolved out of the treatment setting. Extensive experience with tamoxifen, a first-generation selective estrogen receptor modulator (SERM) showing efficacy, first, in the treatment of advanced breast cancer and, subsequently, as adjuvant therapy for early stage disease established the safety of this agent. Cumulative data from multiple adjuvant studies documented the efficacy of tamoxifen in reducing second primary breast cancers in the contralateral breast, supporting its potential as a chemopreventive agent for breast cancer. The safety and second primary data on tamoxifen, together with extensive information on its pharmacokinetics, metabolism, and antitumor effects, as well as its potentially beneficial effects on lipid metabolism and osteoporosis, led the National Surgical Adjuvant Breast and Bowel Project (NSABP) to select tamoxifen for testing in the first prospective randomized phase III trial of the efficacy of a chemopreventive agent for preventing breast cancer in women at increased risk of the disease. Accordingly, in 1992 the NSABP started the Breast Cancer Prevention Trial (P-1) in which 13,388 women 35 years of age who were at increased risk of breast cancer according to Gail model risk factors [family history, age, and personal history (i.e., age at first birth, age at menarche, previous breast biopsies)] were randomized to tamoxifen 20 mg/day or placebo for 5 years. Through 69 months of follow-up tamoxifen reduced the risk of invasive breast cancer, primarily estrogen receptor-positive tumors, by 49% (two-sided p < 0.00001). Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided p < 0.002). In addition, tamoxifen reduced fractures of the hip, radius, and spine, but it had no effect on the rate of ischemic heart disease. As previously shown, the rates of endometrial cancer and vascular events increased with tamoxifen. With the P-1 results establishing tamoxifen as the standard of care for the primary chemoprevention of breast cancer in high-risk women, concern over the side effects of tamoxifen has prompted a continuing search for an agent that displays a more desirable efficacy/toxicity profile. Raloxifene, a second-generation SERM approved for the prevention of osteoporosis in postmenopausal women, displays antiestrogenic properties in the breast and possibly the endometrium, and estrogenic effects in the bone and on the lipid profile, suggesting it as a candidate for comparison with the chemopreventive standard, tamoxifen. Raloxifene will be compared to tamoxifen in an equivalency trial, the Study of Tamoxifen and Raloxifene (STAR) NSABP P-2, which began in July 1999 at almost 500 centers in North America. The plan is to randomize 22,000 postmenopausal women 35 years of age at increased risk of breast cancer by Gail criteria to tamoxifen 20 mg/day or raloxifene 60 mg/day for 5 years. Study endpoints include invasive and noninvasive breast cancer, cardiovascular disease, endometrial cancer, bone fractures, and vascular events. [source] Outcome of patients after treatment for a squamous cell carcinoma of the oropharynxTHE LARYNGOSCOPE, Issue 3 2009Christof Röösli MD Abstract Objectives: This study evaluates the oncologic outcome with regard to survival and locoregional tumor control in a cohort of patients with oropharyngeal squamous cell carcinoma (OPSCC) treated according to a uniform algorithm. Study Design: Retrospective chart review. Methods: A total of 427 consecutive patients with OPSCC were treated from 1990 to 2006. Treatment modalities were surgery alone (n = 102), surgery with adjuvant radio(chemo)therapy (n = 159), and primary radio(chemo)therapy (n = 166). Study endpoints were the five-year overall survival (OS) and disease-specific survival (DSS) stratified for primary tumor subsite, stage, T and N category, and age. Results: The five-year OS and DSS for the entire cohort were 57.9% and 68.6%, respectively. OS and DSS for surgery alone were 70.3% and 76.5%, for surgery with radiation 66.6% and 78.9%, and for primary radiation 40.8% and 52.6%, respectively. Survival was significantly better for low stages (stage I/II vs. III/IV), small tumors (T1/2 vs. T3/4), limited nodal involvement (N0/1 vs. N2/3), and younger age at diagnosis. Conclusions: Together with our previous study on quality of life, we were able to show that our selection process gives excellent oncologic outcome in combination with high levels of function and quality of life. Surgery alone for early OPSCC and surgery followed by radiation for advanced OPSCC remain valuable treatment options. Primary radiochemotherapy is a strong alternative for patients who are not candidates for function-preserving surgery. Laryngoscope, 119:534,540, 2009 [source] Impact of coronary artery disease on outcomes after transcatheter aortic valve implantation,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 2 2010Jean-Bernard Masson MD Abstract Background: Coronary artery disease (CAD) negatively impacts prognosis of patients undergoing surgical aortic valve replacement and revascularization is generally recommended at the time of surgery. Implications of CAD and preprocedural revascularization in the setting of transcatheter aortic valve implantation (TAVI) are not known. Method: Patients who underwent successful TAVI from January 2005 to December 2007 were retrospectively divided into five groups according to the extent of CAD assessed with the Duke Myocardial Jeopardy Score: no CAD, CAD with DMJS 0, 2, 4, and ,6. Study endpoints included 30-day and 1-year survival, evolution of symptoms, left ventricular ejection fraction (LVEF), and mitral regurgitation (MR) and need of revascularization during follow-up. Results: One hundred and thirty-six patients were included, among which 104 (76.5%) had coexisting CAD. Thirty-day mortality in the five study groups was respectively 6.3, 14.6, 7.1, 5.6, and 17.7% with no statistically significant difference between groups (P = 0.56). Overall survival rate at one year was 77.9% (95% CL: 70.9, 84.9) with no difference between groups (P = 0.63). Symptoms, LVEF, and MR all significantly improved in the first month after TAVI, but the extent of improvement did not differ between groups (P > 0.08). Revascularization after TAVI was uncommon. Conclusion: The presence of CAD or nonrevascularized myocardium was not associated with an increased risk of adverse events in this initial cohort. On the basis of these early results, complete revascularization may not constitute a prerequisite of TAVI. This conclusion will require re-assessment as experience accrues in patients with extensive CAD. © 2010 Wiley-Liss, Inc. [source] Citalopram 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] Olanzapine monotherapy for acute depression in patients with bipolar I or II disorder: results of an 8-week open label trialHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2010William V. Bobo Abstract We evaluated the efficacy, tolerability, and safety of olanzapine monotherapy in 20 adult patients with bipolar I or II disorder, depressed phase. Patients received open-label olanzapine monotherapy (mean modal dose, 15,mg/day) for 8 weeks. Assessments of psychopathology (Montgomery,Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology [QIDS-SR-16], Young Mania Rating Scale [YMRS]), clinical global state (Clinical Global Impressions [CGI] scale), and safety/tolerability were performed at baseline, and at 1, 2, 4, 6, and 8 weeks. Seventeen patients (85.0%) completed the study. Improvement in MADRS total scores was observed after the first week of treatment, and at all remaining follow-up time points (p,,,0.005). Parallel improvement in QIDS-SR-16 (p,<,0.001) and CGI-Severity (p,<,0.001) was observed between baseline and study endpoint. Nine (45%) subjects achieved positive treatment response, eight of whom (40%) also achieved symptom remission. There were significant increases in weight (+3.2,kg, p,=,0.001) and body mass index (+1.1,kg/m2, p,=,0.001), but not fasting glucose or lipids, with the exception of reduced triglyceride levels in the overall sample, and reduced HDL cholesterol in females. Olanzapine may be an effective, well-tolerated option for treating acute non-psychotic depression across a variety of bipolar disorder subtypes. Copyright © 2009 John Wiley & Sons, Ltd. [source] Efficacy and tolerability of quetiapine in patients with schizophrenia who switched from haloperidol, olanzapine or risperidoneHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2005Ilkka Larmo Abstract A post hoc analysis of the SPECTRUM trial was carried out to evaluate whether the improvements in efficacy and tolerability gained on switching to quetiapine occurred consistently for patients previously treated with either: haloperidol (n,=,43); olanzapine (n,=,66); or risperidone (n,=,55) monotherapy. Patients were initiated with quetiapine to 400,mg/day over 7 days, and then flexibly dosed (300,750,mg/day) for 11 weeks. The mean (SD) modal dose of quetiapine was 501 (138),mg/day in the haloperidol subgroup, 472 (147),mg/day in the olanzapine subgroup and 485 (141),mg/day in the risperidone subgroup at the study endpoint. Switching to quetiapine induced significant improvements from baseline in PANSS scores, with least square mean changes in total scores of ,32.5, ,15.4, and ,18.5 for patients previously treated with haloperidol, olanzapine and risperidone, respectively, (all p,<,0.001 vs baseline). Significant improvements were also noted in CDSS scores, particularly for patients clinically depressed at baseline (all p,<,0.001 vs baseline). There were significant reductions in EPS on the SAS and BAS for all subgroups (all p,<,0.001 vs baseline). Switching to quetiapine produced efficacy and tolerability benefits regardless of whether their previous antipsychotic was haloperidol, olanzapine or risperidone. Copyright © 2005 John Wiley & Sons, Ltd. [source] Effect of Teriparatide {rhPTH(1-34)} on BMD When Given to Postmenopausal Women Receiving Hormone Replacement TherapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2006Louis G Ste-Marie Abstract The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone. Introduction: Teriparatide {rhPTH(1-34)}, given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT. Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 ,g/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400,1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA. Results: Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group. Conclusions: Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar. [source] Conversion from a calcineurin inhibitor to everolimus therapy in maintenance liver transplant recipients: A prospective, randomized, multicenter trialLIVER TRANSPLANTATION, Issue 10 2009Paolo De Simone Calcineurin inhibitors (CNIs) contribute to renal dysfunction following liver transplantation. This prospective, randomized, multicenter, 6-month study (with an additional 6 months of follow-up) evaluated whether everolimus with CNI reduction or discontinuation would improve renal function in maintenance liver transplant recipients experiencing CNI-related renal impairment. Patients started everolimus therapy with CNI reduction or discontinuation (n = 72) or continued receiving standard-exposure CNI (n = 73). At month 6, 80% of the patients who had converted to everolimus had discontinued the CNI. The mean change in creatinine clearance (CrCl) from baseline to month 6 was similar between groups (everolimus, 1.0 ± 10.2 mL/minute; controls, 2.3 ± 7.8 mL/minute; P = 0.46), so the primary study endpoint (8 mL/minute difference in the change in CrCl) was not achieved. Among patients who continued everolimus according to the protocol, the mean increase in CrCl was 2.1 (n = 53) and 3.8 mL/minute (n = 38) at months 6 and 12, respectively, versus 2.4 (n = 68) and 3.5 mL/minute in controls (n = 51). The high frequency of CNI dose reductions in controls (77% of the patients) and the relatively long mean time post-transplant (>3 years) likely contributed to the small difference in CrCl. Biopsy-proven acute rejection occurred in 1.4% of the patients in each group, with no graft losses. Study drug discontinuation was higher in everolimus-treated patients, and adverse events were more frequent. These data demonstrate that everolimus allows for discontinuation or a major reduction of CNI exposure in liver allograft recipients suffering CNI-related renal dysfunction without a loss of efficacy. Trials targeting earlier conversion post-transplantation are required to confirm the efficacy and safety of everolimus for improving renal function after liver transplantation. Liver Transpl 15:1262,1269, 2009. © 2009 AASLD. [source] Treatment of Premature Ejaculation in the Asia-Pacific Region: Results from a Phase III Double-blind, Parallel-group Study of DapoxetineTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Chris McMahon MBBS, FAChSHM ABSTRACT Introduction., Dapoxetine is a short-acting selective serotonin reuptake inhibitor that was recently approved for the on-demand treatment of premature ejaculation (PE). Aim., To evaluate the efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE from the Asia-Pacific region. Methods., This randomized, double-blind, parallel-group, placebo-controlled trial enrolled men who were 18 years or older; in a monogamous, heterosexual relationship for at least 6 months; met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, criteria for PE for at least 6 months; and had an intravaginal ejaculatory latency time (IELT) of 2 minutes or less in at least 75% of sexual intercourse episodes. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1,3 hours before intercourse) for 12 weeks. Main Outcome Measures., Stopwatch-measured Average IELT, the Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change in PE, treatment-emergent adverse events (TEAEs). Results., Of the 1,067 subjects randomized, 858 completed the study. Mean Average IELT increased from approximately 1.1 minutes at baseline (across groups) to 2.4, 3.9, and 4.2 minutes with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively, and geometric mean Average IELT increased from approximately 0.9 minutes at baseline (across groups) to 1.8, 2.7, and 3.1 minutes, respectively (fold-increases of 2.0, 2.8, and 3.3, respectively). All PEP measures and the CGI of change were significantly improved with dapoxetine vs. placebo at study endpoint (P , 0.005 for all). The most common TEAEs with dapoxetine included nausea, dizziness, somnolence, headache, vomiting, diarrhea, and nasopharyngitis; TEAEs led to discontinuation in 0.3%, 1.7%, and 5.1% of subjects with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively. Conclusions., Dapoxetine treatment significantly prolonged IELT and improved PEP measures and was generally well tolerated in men with PE in the Asia-Pacific region. McMahon C, Kim SW, Park NC, Chang C, Rivas D, Tesfaye F, Rothman M, and Aquilina J on behalf of the dapoxetine 3003 study investigators. Treatment of premature ejaculation in the Asia-Pacific region: Results from a phase III double-blind, parallel-group study of dapoxetine. J Sex Med 2010;7:256,268. [source] Alleviating the Burden of Small-for-Size Graft in Right Liver Living Donor Liver Transplantation Through Accumulation of ExperienceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010S. C. Chan The issue of small-for-size graft (SFSG) containing the middle hepatic vein in right liver living donor liver transplantation from 1996 to 2008 (n = 320) was studied. Characteristics of donors, grafts and recipients were comparable between Era I (first 50 cases) and Era II (next 270 cases) except that the median model for end-stage liver disease (MELD) score was higher in Era I (29 vs. 24; p = 0.024). The median graft to standard liver volume ratio (G/SLV) in Era I was 49.0% (range, 32.8,86.2%), versus 49.3% (range, 28.4,89.4%) in Era II (p = 0.498). Hospital mortality rate, the study endpoint, dropped from 16.0% (8/50) in Era I to 2.2% (6/270) in Era II (p = 0.000). Univariate analysis showed that MELD score (p = 0.002), pretransplant hepatorenal syndrome (p = 0.000) and Era I (p = 0.000) were significant in hospital mortality. Logistic regression analysis showed that only Era I (relative risk 9.758; 95% confidence interval, 2.885,33.002; p = 0.000) was significant. In Era I, G/SLV<40% had a relative risk of 7.8 (95% confidence interval, 1.225,49.677; p = 0.030). The hospital mortality rates for G/SLV<40% were 50% (3/6) and 1.9% (1/52) in Era I and II respectively. In conclusion, through accumulation of experience, SFSG became less important as a factor in hospital mortality. [source] Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorderBIPOLAR DISORDERS, Issue 6 2010Mani N Pavuluri Pavuluri MN, Henry DB, Findling RL, Parnes S, Carbray JA, Mohammed T, Janicak PG, Sweeney JA. Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder. Bipolar Disord 2010: 12: 593,605. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objective:, To determine the relative effects of risperidone and divalproex in pediatric mania. Methods:, This is a double-blind, randomized, outpatient clinical trial with 66 children and adolescents (mean age = 10.9 ± 3.3 years; age range = 8,18 years) with mania who were randomly assigned to either risperidone (0.5,2 mg/day, n = 33) or divalproex (60,120 ,g/mL, n = 33) for a six-week period. Measures included the Young Mania Rating Scale (YMRS) and Child Depression Rating Scale-Revised (CDRS-R). Results:, Mixed-effects regression models, with interaction between time and the active drug as predictors, found that the risperidone group had more rapid improvement than the divalproex group (p < 0.05), although final scores did not differ significantly between groups. Mixed models using only those subjects who completed the six-week study found similar results. The response rate on YMRS was 78.1% for risperidone and 45.5% for divalproex (p < 0.01). The remission rate for risperidone was 62.5%, compared with 33.3% for divalproex (p < 0.05). Improvement on the CDRS-R was significantly higher for the risperidone group relative to the divalproex group (p < 0.05). There were no significant differences between groups in safety, but subject retention was significantly higher at study endpoint in the risperidone group (p < 0.01). Dropout rate was 24% in the risperidone group and 48% in the divalproex group, with increased irritability being the most common reason for dropout in the latter. There was no significant weight gain in either group. Conclusion:, Results suggest that risperidone was associated with more rapid improvement and greater reduction in manic symptoms compared to divalproex. Although the results suggest that both drugs are safe, risperidone's lower attrition rate and lower rate of adverse events may suggest better toleration. Clinical trials with larger samples are required to confirm these preliminary findings. [source] Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice.BIPOLAR DISORDERS, Issue 5 2010The 6th trial of the Danish University Antidepressant Group (DUAG-6) Licht RW, Nielsen JN, Gram LF, Vestergaard P, Bendz H. Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG-6). Bipolar Disord 2010: 12: 483,493. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives:, In industry-generated pivotal studies, lamotrigine has been found to be superior to placebo and comparable to lithium in the maintenance treatment of bipolar I disorder. Here, we directly compared lamotrigine to lithium under conditions similar to clinical routine conditions. Methods:, Adult bipolar I disorder patients with at least two episodes within the last five years and an index episode requiring treatment were randomized to lithium (n = 78; doses adjusted to obtain serum levels of 0.5,1.0 mmol/L) or to lamotrigine (n = 77; up-titrated to 400 mg/day) as maintenance treatments. Randomization took place when clinically appropriate, and comedication was allowed within the first six months after randomization. The patients were enrolled from March 2001 to December 2005, and observations were censored December 2006, allowing a subgroup of patients to be followed for more than five years. The primary outcome measure was time to predefined endpoints indicating insufficient maintenance treatment, and the major secondary outcome measure was time to any study endpoint. Data were analyzed primarily by Cox proportional regression models. Results:, For the primary outcome measure, the crude Hazard Rate Ratio (HRR) (lamotrigine relative to lithium) was 0.92 [95% confidence interval (CI): 0.60,1.40]. When the primary endpoints were broken down by polarity, the HRRs (lamotrigine relative to lithium) for mania and depression were, respectively, 1.91 (95% CI: 0.73,5.04) and 0.69 (95% CI: 0.41,1.22). There was no between-group difference in terms of staying in study [HRR: 0.85 (95% CI: 0.61,1.19)]. Most treatment failures occurred within the first 1.5 years of treatment, and, among patients followed for at least five years, practically no patients were maintained successfully on monotherapy with either of the drugs. The lithium-treated patients reported diarrhea, tremor, polyuria, and thirst more frequently. Two cases, probably lamotrigine-related, of benign rash occurred. Conclusions:, No differences in maintenance effectiveness between lithium and lamotrigine could be demonstrated. Lamotrigine was better tolerated than lithium, but apparently this did not influence the outcome. [source] Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot studyBIPOLAR DISORDERS, Issue 6 2007Carlos A Zarate Jr Objectives:, Considerable preclinical biochemical and behavioral data suggest that protein kinase C inhibition would bring about antimanic effects. Notably, the structurally highly dissimilar antimanic agents lithium and valproate, when administered in therapeutically relevant paradigms, attenuate protein kinase C inhibition function. There is currently only one relatively selective protein kinase C inhibitor that crosses the blood,brain barrier available for human use , tamoxifen. Our group recently conducted a single-blind study with tamoxifen in acute mania and found that it significantly decreased manic symptoms within a short period of time (3,7 days). In this study, we investigated whether antimanic effects can be achieved with a protein kinase C inhibitor in subjects with mania. Methods:, In a double-blind, placebo-controlled study, 16 subjects with bipolar disorder, manic or mixed, with or without psychotic features, were randomly assigned to receive tamoxifen (20,140 mg/day; n = 8) or placebo (n = 8) for three weeks. Primary efficacy was assessed by the Young Mania Rating Scale. Results:, Subjects on tamoxifen showed significant improvement in mania compared to placebo as early as five days, an effect that remained significant throughout the three-week trial. The effect size for the drug difference was very large (d = 1.08, 95% confidence interval 0.45,1.71) after three weeks (p = 0.001). At study endpoint, response rates were 63% for tamoxifen and 13% for placebo (p = 0.12). Conclusions:, Antimanic effects resulted from a protein kinase C inhibitor; onset occurred within five days. Large, controlled studies with selective protein kinase C inhibitors in acute mania are warranted. [source] Conversion from valproic acid onto topiramate in adolescents and adults with epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009A. Schreiner Objective,,, To explore efficacy and tolerability outcomes of topiramate (TPM) in patients with epilepsy transitioning from valproic acid (VPA) because of insufficient efficacy and/or tolerability onto TPM. Methods,,, Multicenter, open label, single arm, non-interventional study examining patients (,12 years) with epilepsy, transitioning onto TPM from baseline mono-or combination therapy with VPA. TPM was added onto the existing antiepileptic drug (AED) treatment and started at a dose of 25 mg once daily. The dose was titrated up with 25 mg/day increments, once every 1,2 weeks, until a final dose between 50,200 mg/day was reached. Based on clinical judgment, the treating physician decided whether or not and when the existing AED treatment especially with VPA could be withdrawn. Documented were type and frequency of seizures, TPM dose, quality of life (QOLIE-10 questionnaire), subjective perception of improvement, and adverse events (AE). Results,,, One hundered and forty-seven patients (59% women, mean age 41 years) switched from baseline VPA treatment onto TPM because of insufficient efficacy (61%) and/or poor tolerability (81%). Average duration of follow-up was 20.3 weeks with an overall discontinuation rate of 16.3% of patients, mainly because of AE (in 8.2% of 147 patients). At study endpoint, the intended shift to TPM monotherapy was achieved in 70% of patients at a median dose of 150 mg/day. A seizure reduction of ,50% was achieved in 75% of patients in the last scheduled period (week 8,20), and 51% of patients entering that period remained seizure-free. Quality of life improved significantly as compared with baseline for all domains of QOLIE-10 (P < 0.001). Most frequent AEs were weight decrease (4.8%), paraesthesia and fatigue (4.1% each), speech disorder and headaches (2.7% each). Conclusions,,, In patients with epilepsy not satisfactorily treated with VPA, conversion to TPM was associated with improved seizure control as well as improvement in several aspects of quality of life. [source] Risperidone in the treatment of disruptive behavioural symptoms in children with autistic and other pervasive developmental disordersCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 2 2005Richard ReadingArticle first published online: 16 FEB 200 Risperidone in the treatment of disruptive behavioural symptoms in children with autistic and other pervasive developmental disorders . SheaS, TurgayA, CarrollA, SchulzM, OrlikH, SmithI & DunbarF. ( 2004 ) Pediatrics , 114 , e634 , e641 . Objective To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioural symptoms in children with autism and other pervasive developmental disorders (PDD). Methods In this 8-week, randomized, double-blinded, placebo-controlled trial, risperidone/placebo solution (0.01,0.06 mg/kg/day) was administered to 79 children who were aged 5,12 years and had PDD. Behavioural symptoms were assessed using the Aberrant Behaviour Checklist (ABC), Nisonger Child Behaviour Rating Form and Clinical Global Impression-Change. Safety assessments included vital signs, electrocardiogram, extrapyramidal symptoms, adverse events and laboratory tests. Results Subjects who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day) experienced a significantly greater mean decrease on the irritability subscale of the ABC (primary endpoint) compared with those who were taking placebo. By study endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline in the irritability score almost double that of placebo-treated subjects (31%). Risperidone-treated subjects also exhibited significantly greater decreases on the other four subscales of the ABC; on the conduct problem, insecure/anxious, hyperactive and overly sensitive subscales of the Nisonger Child Behaviour Rating Form (parent version); and on the Visual Analog Scale of the most troublesome symptom. More risperidone-treated subjects (87%) showed global improvement in their condition compared with the placebo group (40%). Somnolence, the most frequently reported adverse event, was noted in 72.5% vs. 7.7% of subjects (risperidone vs. placebo) and seemed manageable with dose/dose-schedule modification. Risperidone-treated subjects experienced statistically significantly greater increases in weight (2.7 vs. 1.0 kg), pulse rate and systolic blood pressure. Extrapyramidal symptoms scores were comparable between groups. Conclusions Risperidone was well-tolerated and efficacious in treating behavioural symptoms associated with PDD in children. [source] Transillumination by light-emitting diode facilitates peripheral venous cannulations in infants and small childrenACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2010K. HOSOKAWA Background: Transillumination facilitates the visualization of peripheral veins in infants and children. The clinical usefulness of light-emitting diode (LED)-powered devices has not been thoroughly studied. Methods: We randomly assigned 136 infants and children weighing <15 kg, undergoing general anesthesia, to red LED-powered transillumination (TM group, n=67) vs. the usual method (UM group, n=69) of peripheral venous cannulations. Venous puncture was performed following anesthesia induction with sevoflurane and nitrous oxide. The primary and secondary study endpoints were the rate of successful cannulations at initial attempt, and the duration of insertion attempts, respectively. Results: The median score of the estimated cannulation difficulty before attempted puncture was similar in both groups. The success rates at first attempt were 75% and 61% (NS) and mean±SD times to successful venous access were 47±34 and 68±66 s (NS) in the TM and UM groups, respectively. The cannulation procedures were completed significantly earlier in the TM group than in the UM group (hazard ratio, 1.59; 95% confidence interval, 1.03,2.47; P=0.03). In the subgroup of infants and children <2 years old, venous cannulation was successful at first attempt in 73% and 49% in the TM group (n=44) and in the UM group (n=47), respectively (P=0.03). Conclusions: LED-powered transillumination devices facilitated peripheral venous cannulations in small infants and children. [source] Evaluating outpatient pharmacy services: a literature review of specialist heart failure servicesINTERNATIONAL JOURNAL OF PHARMACY PRACTICE, Issue 1 2006Tracey-Lea Hargraves Pharmacist (formerly) Objective To identify appropriate methods to evaluate a specialist pharmacy service for heart failure patients in an ambulatory care setting. Method An extensive literature review was undertaken to identify the published data on evaluative studies of specialist pharmacy services, including those directed at heart failure patients in an ambulatory care model of service provision. Key findings Six studies were identified evaluating outpatient pharmacy services for heart failure. The pharmacy services provided in these settings were not well defined. The impact of the pharmacist was compared to ,usual care', that is care delivered without a pharmacist, by either a prospective randomised controlled trial (RCT), or before and after studies. In most cases the service was delivered by one pharmacist at one site. Services were primarily targeted at patients and focused on medication and lifestyle education, adverse drug reaction monitoring, and compliance/adherence. In all studies, there was a trend for improvement in the outcomes measured. Different study endpoints were examined, including process indicators such as compliance and outcome measures such as morbidity (clinical), quality of life (humanistic), and hospital admissions (economic). The ideal evaluative study would be an adequately powered, prospective, randomised controlled trial, comparing the effect of the pharmacist service to usual care (without the specified pharmacy service). Appropriate study endpoints including process indicators and outcome measures are needed. Identification of specific components and the extent of the service that would provide the most benefit to selected patient groups would be of interest. Conclusions Specialist ambulatory care pharmacy services have not been well defined or evaluated in the literature. Limited randomised controlled data exist. [source] The Efficacy of Acamprosate in the Maintenance of Abstinence in Alcohol-Dependent Individuals: Results of a Meta-AnalysisALCOHOLISM, Issue 1 2004Karl Mann Abstract: Background: A number of clinical trials have been undertaken to determine the efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals. However, the reported differences in patient populations, treatment duration, and study endpoints make comparisons difficult. An assessment of the efficacy of treatment with acamprosate was, therefore, undertaken using meta-analytical techniques. Methods: All randomized, placebo-controlled trials (RCTs) that fulfilled predetermined criteria were identified using (1) a language unrestricted search of 10 electronic databases; (2) a manual search of relevant journals, symposia, and conference proceedings; (3) cross-referencing of all identified publications; (4) personal communications with investigators; and (5) scrutiny of Merck-Santé's internal reports of all European trials. Study quality was assessed, independently, by three blinded workers. Key outcome data were identified; some outcome variables were recalculated to ensure consistency across trials. The primary outcome measure was continuous abstinence at 6 months; abstinence rates were determined by estimating Relative Benefit (RB). Results: A total of 19 published 1 unpublished RCTs were identified that fulfilled the selection criteria; 3 were excluded because the documentation available was insufficient to allow adequate assessment. The remaining 17 studies, which included 4087 individuals, 53% of whom received active drug, were of good quality and were otherwise reasonably comparable. There was no evidence of publication bias. Continuous abstinence rates at 6 months were significantly higher in the acamprosate-treated patients (acamprosate, 36.1%; placebo, 23.4%; RB, 1.47; [95% confidence intervals (CI): 1.29,1.69]; p < 0.001). This effect was observed independently of the method used for assigning missing data. The effect sizes in abstinent rates at 3, 6, and 12 months were 1.33, 1.50, and 1.95, respectively. At 12 months, the overall pooled difference in success rates between acamprosate and placebo was 13.3% (95% CI, 7.8,18.7%; number needed to treat, 7.5). Acamprosate also had a modest but significant beneficial effect on retention (6.01%; [95% CI, 2.90,8.82]; p= 0.0106). Conclusion:: Acamprosate has a significant beneficial effect in enhancing abstinence in recently detoxified, alcohol-dependent individuals. [source] Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy to treat gastric cancer with ascites and/or peritoneal carcinomatosis: Results from a Chinese centerJOURNAL OF SURGICAL ONCOLOGY, Issue 6 2010Xiao-Jun Yang MD Abstract Background This work was to evaluate cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (GC). Methods CRS and HIPEC were performed on 28 GC patients with peritoneal carcinomatosis (PC) and/or malignant ascites, with survival and perioperative safety as study endpoints. Results A total of 30 CRS and HIPEC procedures were performed. Cytoreduction scores ratings (CCR) were CCR-0 in 11 (39.2%), CCR-1 in 6 (21.4%), CCR-2 in 8 (28.8%), and CCR-3 in 3 (10.6%) cases. The 6-, 12-, 18-, and 24-month survival rates were 75%, 50%, 43%, and 43%, respectively. The median survivals of patients with PCI ,20 and high PCI >20 were 27.7 months (95% CI 15.2,40.3 months) and 6.4 months (95% CI 3.8,8.9 months) (P,=,0.000). The estimated median survival for patients with CCR-0, CCR-1, and CCR-2 and 3 were 43.4 months (95% CI, 26.9,59.9 months), 9.5 months (95% CI 6.4,12.6 months), and 7.5 months (95% CI 3.0,13.6 months) (P,=,0.001, CCR0 vs. CCR1-3). No perioperative death but 1 (3.6%) serious adverse event occurred. Conclusions CRS plus HIPEC could offer survival advantage for selected GC patients with PC and/or ascites, with acceptable safety profile. J. Surg. Oncol. 2010; 101:457,464. © 2010 Wiley-Liss, Inc. [source] Mapping solutions to obesity: lessons from the Human Genome ProjectAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 6 2008Catriona M. F. Bonfiglioli Abstract Objective: To discuss appropriate endpoints for research designed to prevent obesity. Research investigating practical solutions to the complex multi-factorial global obesity epidemic may be stalled by undue emphasis on reduced body weight as the only acceptable endpoint. Approach: Considering prevention research in cardiovascular disease and tobacco control, we contend that investigations of intermediate endpoints make an important contribution to the multi-faceted approach needed to combat the complex problem of obesity. Conclusion: Intermediate endpoints are respected in other public health areas: reductions in risk factors such as high blood cholesterol or smoking are acceptable study endpoints for research aimed at reducing heart disease or lung cancer. Likewise, practical endpoints can be valuable in studies investigating interventions to reduce identified and potential intermediate risk factors for obesity, such as soft drink consumption. Implications: Reduced obesity is the global aim but obesity is not caused by one exposure and will not be solved by a single modality intervention. A wider debate about endpoint selection may assist research which identifies individual building blocks of obesity prevention in the same way as individual gene mapping contributed to the Human Genome Project. [source] Sentinel lymph node biopsy in breast cancer guided by indocyanine green fluorescenceBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2009D. Murawa Background: Sentinel lymph node (SLN) biopsy with radioisotope and blue dye has been used successfully for axillary staging in breast cancer. This study evaluated the feasibility of fluorescence detection of SLNs with indocyanine green (ICG) for lymphatic mapping and SLN biopsy. Methods: Thirty women with breast cancer had a periareolar injection of ICG for fluorescence detection of SLN using a near-infrared camera. Twenty also received 99mTc-labelled sulphur radiocolloid for SLN scintigraphy. All patients underwent axillary lymph node dissection. Detection rate and sensitivity of both methods were the study endpoints. Results: Visualization of lymphatic vessels by fluorescence detection depended on the dose of ICG. ICG imaging identified SLNs in 29 of 30 women (detection rate 97 per cent). Nineteen of 21 patients had metastatic SLN involvement (sensitivity 90 per cent) with false-negative results in two. Among the 20 patients who had both methods, ICG fluorescence and radiocolloid identified SLNs in 20 and 17 patients respectively. Metastatic lymph nodes were diagnosed in 12 and ten of 13 patients (sensitivity 92 and 77 per cent). False-negative rates were 8 and 23 per cent respectively. Conclusion: ICG fluorescence allowed transcutaneous imaging of lymphatic vessels and SLN detection, thus combining the advantages of radioisotope and blue dye methods. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||