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Serious Adverse Events (serious + adverse_event)
Selected AbstractsLong-term safety and efficacy of long-acting risperidone in elderly psychotic patientsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2007Werner Kissling Abstract This subgroup analysis of the 6-month, open-label Switch to Risperidone Microspheres (StoRMi) trial evaluated long-term safety and efficacy of a direct conversion to risperidone long-acting injectable (RLAI) in 52 elderly patients (,65 years) with psychosis stabilized on oral or depot antipsychotic. Study outcomes included adverse events, movement disorder severity, psychiatric symptoms, functional ability, quality of life and patient satisfaction. Change in the Positive and Negative Syndrome Scale at endpoint was the primary efficacy measure. The most common dosage of RLAI used at endpoint was 25,mg every 14 days (60%). The trial was completed by 81% of patients, with six patients discontinuing treatment due to an adverse event. Tolerability was good and most side effects were mild to moderate. Serious adverse events occurred in 11 patients. Two of these (suicidal attempt, n,=,1; exacerbation of disease, n,=,1) were considered possibly related to RLAI. Conversion to RLAI resulted in significant improvements in movement disorder severity, psychiatric symptoms, functional status and patient satisfaction. Mean PANSS total decreased by 15.8 at endpoint, with 23 patients (46.9%) experiencing a ,20% improvement. This post-hoc analysis supports that RLAI is well tolerated and safe in elderly patients with psychotic illnesses switched from stable antipsychotic regimens, and suggests possible efficacy, although inferences are limited. Copyright © 2007 John Wiley & Sons, Ltd. [source] Golimumab, a human anti,tumor necrosis factor , monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: Twenty-four,week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis,ARTHRITIS & RHEUMATISM, Issue 8 2009Paul Emery Objective To assess the safety and efficacy of golimumab in methotrexate (MTX),naive patients with active rheumatoid arthritis (RA). Methods MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1). Results An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P = 0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P = 0.049) and between group 3 (40.5%; P = 0.038) but not group 4 (36.5%; P = 0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound ,5.2%; predefined delta value for noninferiority ,10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively. Conclusion Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns. [source] Phase II study of lenalidomide in patients with metastatic renal cell carcinomaCANCER, Issue 11 2006Toni K. Choueiri MD Abstract BACKGROUND. Lenalidomide (LEN) is a structural and functional analogue of thalidomide that has demonstrated enhanced immunomodulatory properties and a more favorable toxicity profile. A Phase II, open-label study of LEN in patients with metastatic renal cell carcinoma (RCC) was conducted to determine its safety and clinical activity. METHODS. Patients with metastatic RCC received LEN orally at a dose of 25 mg daily for the first 21 days of a 28-day cycle. The primary endpoint was the objective response rate. Time to treatment failure, safety, and survival were secondary endpoints. RESULTS. In total, 28 patients participated in the trial and were included in the current analysis. Three of 28 patients (11%) demonstrated partial responses and continued to be progression-free for >15 months. Eleven patients (39%) had stable disease that lasted >3 months, including 8 patients who had tumor shrinkage. In total, 6 patients (21%) remained on the trial, and 5 additional patients continued to be followed for survival. The median follow-up for those 11 patients was 13.5 months (range, 8.3,17.0 months). The median survival had not been reached at the time of the current report. Serious adverse events included fatigue (11%), skin toxicity (11%), and neutropenia (36%). CONCLUSIONS. LEN demonstrated an antitumor effect in metastatic RCC, as evidenced by durable partial responses. LEN toxicities were manageable. Further studies will be required to assess the overall activity of LEN in patients with metastatic RCC. Cancer 2006. © 2006 American Cancer Society. [source] Tolerability and Safety of Frovatriptan With Short- and Long-term Use for Treatment of Migraine and in Comparison With SumatriptanHEADACHE, Issue 2002Gilles Géraud MD Objective.,To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine. Background.,Frovatriptan is a new, selective serotonin agonist (triptan) developed for the acute treatment of migraine. Dose range-finding studies identified 2.5 mg as the dose that conferred the optimal combination of efficacy and tolerability. Methods.,The tolerability and safety of frovatriptan 2.5 mg were assessed during controlled, acute migraine treatment studies, including a study that compared frovatriptan 2.5 mg with sumatriptan 100 mg, as well as a 12-month open-label study during which patients could take up to three doses of frovatriptan 2.5 mg within a 24-hour period. Safety and tolerability were assessed through the collection of adverse events, monitoring of heart rate and blood pressure performance of 12-lead electrocardiogram, hematology screen, and blood chemistry studies. Results.,In the short-term studies, 1554 patients took frovatriptan 2.5 mg and 838 took placebo. In the 12-month study, 496 patients treated 13 878 migraine attacks. Frovatriptan was well tolerated in the short- and long-term studies with 1% of patients in the short-term studies and 5% of patients in the long-term study withdrawing due to lack of tolerability. The incidence of adverse events was higher in the frovatriptan-treated patients than in the patients who took placebo (47% versus 34%) and the spectrum of adverse events was similar. When compared to sumatriptan 100 mg, significantly fewer patients taking frovatriptan experienced adverse events (43% versus 36%; P=.03) and the number of adverse events was lower (0.62 versus 0.91), there were also fewer adverse events suggestive of cardiovascular symptoms in the frovatriptan group. Analysis of the entire clinical database (n=2392) demonstrated that frovatriptan was well tolerated by the patients regardless of their age, gender, race, concomitant medication, or the presence of cardiovascular risk factors. No effects of frovatriptan on heart rate, blood pressure, 12-lead electrocardiogram, hematology screen, or blood chemistry were observed. No patient suffered any treatment-related serious adverse event. Conclusions.,Short- and long-term use of frovatriptan 2.5 mg was well tolerated by a wide variety of patients. Frovatriptan treatment produced an adverse events profile similar to that of placebo, and in a direct comparison study was better tolerated than sumatriptan 100 mg. [source] Polaprezinc prevents oral mucositis associated with radiochemotherapy in patients with head and neck cancerINTERNATIONAL JOURNAL OF CANCER, Issue 8 2010Tomoko Watanabe Abstract Oral mucositis is frequent but serious adverse event associated with radiotherapy or radiochemotherapy in head and neck cancer severely impairs health-related quality of life, leading to poor prognosis due to discontinuation of the therapy. Although a number of compounds have been tested for prophylaxis of oral mucositis, few of them are satisfactory. We investigated the effect of polaprezinc (zinc L -carnosine), a gastric mucosal protective drug, on radiochemotherapy-induced oral mucositis, pain, xerostomia and taste disturbance in patients with head and neck cancer. Patients were randomly assigned to receive polaprezinc (n = 16) or azulene oral rinse as the control (n = 15). The incidence rates of mucositis, pain, xerostomia and taste disturbance were all markedly lower in polaprezinc group than in control. Moreover, the use of analgesics was significantly (p = 0.003) less frequent and the amount of food intake was significantly (p = 0.002) higher in polaprezinc group than in control. On the other hand, tumor response rate in patients with neoadjuvant radiochemotherapy was not significantly affected by polaprezinc, in which the response rate (complete plus partial response) was 88% for polaprezinc and 92% for control (p = 1.000). Therefore, it is highly assumable that polaprezinc is potentially useful for prevention of oral mucositis and improvement of quality of life without reducing the tumor response. [source] Comparison of Cool Tip Versus 8-mm Tip Catheter in Achieving Electrical Isolation of Pulmonary Veins for Long-Term Control of Atrial Fibrillation: A Prospective Randomized Pilot StudyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2006SANJAY DIXIT M.D. Objective: To compare safety and efficacy of 8-mm versus cooled tip catheter in achieving electrical isolation (EI) of pulmonary veins (PV) for long-term control of atrial fibrillation (AF). Background: There is paucity of studies comparing safety/efficacy of 8-mm and cooled tip catheters in patients undergoing AF ablation. Methods and Results: This was a randomized and patient-blinded study. Subjects were followed by clinic visits (at 6 weeks and 6 months) and transtelephonic monitoring (3-week duration) done around each visit. Primary endpoints were: (1) long-term AF control (complete freedom and/or >90% reduction in AF burden on or off antiarrhythmic drugs at 6 months after a single ablation), and (2) occurrence of serious adverse events (cardiac tamponade, stroke, LA-esophageal fistula, and/or death). Eighty-two patients (age 56 ± 9 years, 60 males, paroxysmal AF = 59) were randomized (42 patients to 8-mm tip and 40 patients to cooled tip). EI of PVs was achieved in shorter time by the 8-mm tip as compared with cooled tip catheter (40 ± 23 minutes vs 50 ± 30 minutes; P < 0.05) but long-term AF control was not different between the two (32 patients [78%] vs 28 patients [70%], respectively; P = NS). One serious adverse event occurred in each group (LA-esophageal fistula and stroke, respectively) and no significant PV stenosis was observed in either. Conclusion: EI of PVs using either 8-mm or cooled tip catheter results in long-term AF control in the majority after a single ablation procedure, with comparable efficacy and safety. [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] Early steroid withdrawal after liver transplantation: The canadian tacrolimus versus microemulsion cyclosporin a trial: 1-year follow-upLIVER TRANSPLANTATION, Issue 6 2003Paul Greig Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (micro-CsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n = 71) or micro-CsA (n = 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone ,0.15 mg/kg/d. In eligible patients, the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved. At 1 year after transplantation, 75% of the tacrolimus patients and 63% of the micro-CsA patients were steroid-free (P = .20). Of all of the patients who became eligible for steroid withdrawal, steroid discontinuation was achieved in over 80%. One-year patient survival was 97% with tacrolimus and 89% with micro-CsA (P = .052). Graft survival was 97% and 86%, respectively (P = .017). The overall incidence of acute rejection during the first year was 35% with tacrolimus and 43% with micro-CsA (P = .26). There was no difference in survival, acute rejection, or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive. Steroid-resistant rejection occurred in 5.6% of the tacrolimus and 9.7% of the micro-CsA patients. One patient, in the micro-CsA group, experienced refractory rejection. Chronic rejection was not observed in either group. The toxicity profiles were similar. Postoperative serum creatinine levels were similar, and dialysis was required in less than 10% of patients in each group. Infectious complications were similar in both groups. Neurotoxicity was a serious adverse event in 13% and 10% of patients receiving tacrolimus and micro-CsA, respectively. Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis. [source] Review article: interstitial nephritis associated with the use of mesalazine in inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2000Corrigan 5-Aminosalicylic acid (5-ASA) has replaced sulphasalazine as first line therapy for mild to moderately active inflammatory bowel disease and is widely used. A number of reports have linked oral 5-ASA therapy to chronic tubulo-interstitial nephritis and this relationship is now well established. Despite increasing recognition of the potential for this serious adverse event, guidelines for monitoring renal function in patients prescribed 5-ASA preparations are not widely employed. Whilst the incidence of this adverse event in the population of patients with inflammatory bowel disease treated with mesalazine is low, the morbidity in an affected individual is high with some cases progressing to end-stage renal disease. Routine monitoring of renal function is simple and inexpensive and could prevent this outcome. Based on the available data, serum creatinine should be estimated prior to commencing treatment, monthly for the first 3 months, 3-monthly for the next 9 months, 6-monthly thereafter and annually after 5 years of treatment. [source] Safety of specific sublingual immunotherapy with SQ standardized grass allergen tablets in childrenPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 6 2007Maria Dolores Ibañez The aim of the study was to confirm the safety of an orodispersible grass allergen tablet 75,000 SQ-T (Grazax®, ALK-Abelló A/S, Hørsholm, Denmark) in children aged 5,12 yr. The study was randomized, double-blinded and placebo-controlled. Sixty children aged 5,12 yr suffering from grass pollen-induced rhinoconjunctivitis (with or without asthma) from five centres in two countries (three in Germany and two in Spain) participated in the study. They were randomized at the ratio of 3:1 as receiving either Grazax or placebo tablet given sublingually once daily for 28 days outside the grass pollen season. A total of 810 treatment-related adverse events were reported in the Grazax group. The majority of these were local reactions in the mouth or throat and were mostly mild (71%) to moderate (27%) in severity and resolved within days. Thirty-five (78%) subjects treated with Grazax and five (33%) treated with placebo reported at least one treatment-related adverse event. Oral pruritus, throat irritation, mouth oedema and ear pruritus appeared as the most frequently reported treatment-related adverse events. 62% (28 of 45) of the actively treated subjects reported oral pruritus, 36% (16 of 45) throat irritation, 31% (14 of 45) mouth oedema and 22% (10 of 45) ear pruritus. Two actively treated subjects withdrew from the study: one subject due to four adverse events (moderate eye pruritus, moderate pharyngolaryngeal pain, moderate non-cardiac chest pain and moderate dysphagia) and one subject due to a serious adverse event (asthmatic attack). The subjects recovered completely from the events. In conclusion, in the present study, Grazax was in general tolerated in a paediatric population and considered suitable for further clinical investigations in children. [source] Safety and immunogenicity of live attenuated varicella vaccine in 9-month-old childrenPEDIATRICS INTERNATIONAL, Issue 6 2000Güler Kanra Background: The present study was conducted to evaluate the safety and immunogenicity of live attenuated varicella vaccine (Oka-strain) in 9-month-old infants. Methods: One hundred and fourteen infants were vaccinated once with live attenuated varicella vaccine (Valrix®; SmithKline Beecham Biologicals, Rixensart, Belgium) containing a mean virus titer of 104.0 plaque-forming units (p.f.u.) per dose. Signs and/or symptoms after vaccination were followed for 42 days. Home visits were made to detect solicited local reactions (0,3 days) and solicited general reactions (0,21 days), as well as unsolicited reactions. Specific varicella antibodies were determined by an indirect immunofluorescence method. The geometric mean titer and seroconversion rate were calculated. Results: Signs and/or symptoms were reported in 47.4% (54/114) of cases following vaccination. The only local symptom reported was pain on digital pressure at the injection site and this was reported in 28.1% (32/114) of infants. General symptoms were reported in 38.6% (44/114) of cases. The most frequently reported findings were fever (27.2%), which was mostly mild, restlessness (20.2%) and cough (11.4%). Only four unsolicited symptoms were reported and they were all unrelated to vaccination. No serious adverse event was reported. Of the 109 infants included in the immunogenicity analysis, 105 were seronegative and four were seropositive for antibodies against varicella before vaccination. The vaccine elicited seroconversion in 97.1% of initially seronegative cases. The post-vaccination geometric mean titer for these infants was 30.9 geometric mean titer (GMT). Conclusions: The vaccine was found to be safe and immunogenic when given to infants as young as 9 months of age. This may be of clinical significance during outbreaks of varicella and especially for developing countries. [source] Report of a second serious adverse event in a clinical trial of gene therapy for X-linked severe combined immune deficiency (X-SCID)THE JOURNAL OF GENE MEDICINE, Issue 3 2003Position of the European Society of Gene Therapy (ESGT) No abstract is available for this article. [source] A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study of Efficacy and Safety of Ocinaplon (DOV 273,547) in Generalized Anxiety DisorderCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 2 2010Pál Czobor Preclinical studies demonstrated that ocinaplon, a positive allosteric modulator of GABAA receptors, possesses anxiolytic-like actions at doses devoid of the side effects typically associated with benzodiazepines. The aim of this study was to evaluate the effects of ocinaplon in a multicenter, double-blind proof-of-concept trial of male and female outpatients who met DSM-IV criteria for GAD with no coexisting depression, and had a baseline score of ,20 on the Hamilton Scale for Anxiety (HAM-A). Patients with <20% reduction in HAM-A to placebo in a single-blind 7-day run-in period were randomly assigned to treatment with ocinaplon 90 mg t.i.d. (n = 31) or placebo for 28 days (n = 29). Ocinaplon was more effective than placebo in reducing HAM-A scores (P= 0.009). Patients assigned to ocinaplon exhibited a mean improvement of 14.2 points (SE = 2.6) on the total score of the HAM-A scale at the conclusion of the trial, while patients assigned to placebo obtained a mean improvement of 6.3 points (SE = 2.0). A significant (P= 0.023) difference in improvement between ocinaplon and placebo was observed beginning at and continuing from 1-week after the initiation of dosing. The proportion of patients with treatment-emergent adverse events (TEAE) was not statistically significant between ocinaplon and placebo. One serious adverse event (SAE) occurred in the ocinaplon group that was considered possibly related to study medication (icterus following transaminase elevations). The patient had preexisting medical conditions that may have contributed to this SAE. A full recovery was observed with no residual effects. The overall safety profile revealed no patterns of TEAEs, including those effects typically associated with other anxiolytic and/or benzodiazepine compounds, such as sedation. Ocinaplon appears to be a well-tolerated and effective treatment for GAD. It produces a rapid onset of anxiolytic action absent the side effects (e.g., dizziness, sedation) typically reported following anxiolytic doses of benzodiazepines. [source] Botulinum Toxin Type A Treatment of Multiple Upper Facial Sites: Patient-Reported OutcomesDERMATOLOGIC SURGERY, Issue 2007JEAN CARRUTHERS MD BACKGROUND Aesthetic treatment planning must address subjects' goals and include subject-reported outcomes. OBJECTIVE The objective was to compare the effect of botulinum neurotoxin type A (BoNTA) with placebo on subject-reported outcomes and to assess the utility of 64 U of BoNTA to treat the entire upper face. METHODS Forty female subjects were randomized to receive 64 U of BoNTA or identical placebo injections (double-masked) divided among 16 sites of the upper face and were followed for 12 weeks. Subjects unimproved at Week 4 were eligible for open-label BoNTA treatment and were followed through Week 16. Main outcome measures were scores on seven items of the Facial Line Outcomes Questionnaire (FLO-7) and results on the Self-Perception of Age (SPA) for assessing age of appearance relative to actual age. RESULTS BoNTA treatment resulted in significant improvements on the FLO-7 scores that were maintained throughout the study. BoNTA treatment also reduced age of appearance in a majority of subjects. Placebo had no effects on any measure. No serious adverse events occurred. CONCLUSION Sixty-four-unit BoNTA treatment of upper facial rhytids safely and significantly improves subject-reported outcomes, as measured by the FLO-7 and SPA, and results in a younger, more satisfying, relaxed appearance. [source] Rhabdomyolysis and brain ischemic stroke in a heroin-dependent male under methadone maintenance therapyACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2009W.-Y. Hsu Objective:, There are several complications associated with heroin abuse, some of which are life-threatening. Methadone may aggravate this problem. Method:, A clinical case description. Results:, A 33-year-old man presented with rhabdomyolysis and cerebral ischemic stroke after intravenous heroin. He had used heroin since age 20, and had used 150 mg methadone daily for 6 months. He was found unconsciousness at home and was sent to our hospital. In the ER, his opiate level was 4497 ng/ml. In the ICU, we found rhabdomyolysis, acute renal failure and acute respiratory failure. After transfer to an internal ward, we noted aphasia and weakness of his left limbs. After MRI, we found cerebral ischemic infarction. Conclusion:, Those using methadone and heroin simultaneously may increase risk of rhabdomyolysis and ischemic stroke. Patients under methadone maintenance therapy should be warned regarding these serious adverse events. Hypotheses of heroin-related rhabdomyolysis and stroke in heroin abusers are discussed. [source] Systemic adverse events following botulinum toxin A therapy in children with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2010KRISHANT NAIDU Aim, We studied the incidence of incontinence and respiratory events in children with cerebral palsy who received injections of botulinum toxin A (BoNT-A). Method, We used multivariable logistic regression to investigate relationships between (BoNT-A) dose, Gross Motor Function Classification System (GMFCS) level, and the incidence of bladder or bowel incontinence, unplanned hospital admission, emergency department consultation or prescription of antibiotics for respiratory symptoms, and diagnosis of upper respiratory tract infection. Results, Of 1980 injection episodes in 1147 children (mean age 4y 7mo, SD 1y 10mo, range 9mo,23y), 488 (25%) were in children with unilateral involvement and 1492 (75%) in children with bilateral involvement. At the time of injection 440 (22.2%) of children were at GMFCS level I, 611 (30.9%) were at level II, 330 (16.7%) were at level III, 349 (17.6%) were at level IV, and 250 (12.6%) were at level V. The incidence of serious adverse events was low, with 19 episodes of incontinence (1% of injection episodes) and 25 unplanned hospital admissions due to respiratory symptoms (1.3%). Incontinence typically resolved spontaneously 1 to 6 weeks after injection. The incidence of adverse events was associated with GMFCS level and dose of BoNT-A. Interpretation, The incidence of serious adverse events was low but suggests systemic spread as well as a procedural effect. We recommend reviewing upper dose limits for children at all GMFCS levels, particularly those at levels IV and V with a history of aspiration and respiratory disease. In these children, alternatives to mask anaesthesia may be particularly important. [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] Safety, tolerability, and efficacy of endoscopic low-pressure liquid nitrogen spray cryotherapy in the esophagusDISEASES OF THE ESOPHAGUS, Issue 1 2010Bruce D. Greenwald SUMMARY Endoscopic cryotherapy is a new technique for ablation of esophageal dysplasia and neoplasia. Preliminary studies have shown it to be safe and effective for this indication. The objective of this study is to characterize safety, tolerability, and efficacy of low-pressure liquid nitrogen endoscopic spray cryotherapy ablation in a large cohort across multiple study sites. Parallel prospective treatment studies at four tertiary care academic medical centers in the U.S. assessed spray cryotherapy in patients with Barrett's esophagus with or without dysplasia, early stage esophageal cancer, and severe squamous dysplasia who underwent cryotherapy ablation of the esophagus. All patients were contacted between 1 and 10 days after treatment to assess for side effects and complications of treatment. The main outcome measurement was the incidence of serious adverse events and side effects from treatment. Complete response for high-grade dysplasia (HGD) (CR-HGD), all dysplasia (CR-D), intestinal metaplasia (CR-IM) and cancer (CR-C) were assessed in patients completing therapy during the study period. A total of 77 patients were treated for Barrett's high-grade dysplasia (58.4%), intramucosal carcinoma (16.9%), invasive carcinoma (13%), Barrett's esophagus without dysplasia (9.1%), and severe squamous dysplasia (2.6%). Twenty-two patients (28.6%) reported no side effects throughout treatment. In 323 procedures, the most common complaint was chest pain (17.6%) followed by dysphagia (13.3%), odynophagia (12.1%), and sore throat (9.6%). The mean duration of any symptoms was 3.6 days. No side effects were reported in 48% of the procedures (155/323). Symptoms did not correlate with age, gender, diagnosis, or to treatment early versus late in the patient's or site's experience. Logit analysis showed that symptoms were greater in those with a Barrett's segment of 6 cm or longer. Gastric perforation occurred in one patient with Marfan's syndrome. Esophageal stricture developed in three, all successfully treated with dilation. In 17 HGD patients, cryotherapy produced CR-HGD, CR-D, and CR-IM of 94%, 88%, and 53%, respectively. Complete regression of cancer and HGD was seen in all seven patients with intramucosal carcinoma or stage I esophageal cancer. Endoscopic spray cryotherapy ablation using low-pressure liquid nitrogen in the esophagus is safe, well-tolerated, and efficacious. [source] Prospective outcome of early intervention for individuals at ultra-high-risk for psychosisEARLY INTERVENTION IN PSYCHIATRY, Issue 4 2008GeumSook Shim Abstract Aim: Based on previous reports of second-generation antipsychotic agents having a beneficial effect on prodromal symptoms, we investigated the effectiveness and tolerability of atypical antipsychotic therapies in individuals at high risk for developing psychosis. Methods: We examined prodromal symptoms and functioning in individuals at ultra-high-risk for psychosis using an uncontrolled prospective design with pre- and post-treatment measures. Results: Of the 27 subjects taking antipsychotics during the study period, 15 took part in at least one follow-up assessment. Overall Com prehensive Assessment of At-Risk Mental States scores significantly improved at the last evaluation point, with a medium-size effect of Cohen's d = 0.54 (95% confidence interval, ,0.02 to 1.08) (mean follow-up period = 8.8; SD = 8.3 months). Depression and anxiety symptoms were markedly reduced, and global and social functioning also significantly improved. Of the 27 subjects, two (7.4%) converted to psychosis and 16 (59.3%) experienced at least one treatment-emergent adverse event, but no subjects exhibited serious adverse events. Conclusions: The results of this study support treating high-risk individuals with antipsychotics to reduce prodromal symptoms with adequate safety. [source] Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependenceADDICTION, Issue 1 2010Marie Longo ABSTRACT Aim To investigate the safety and efficacy of once-daily supervised oral administration of sustained-release dexamphetamine in people dependent on methamphetamine. Design Randomized, double-blind, placebo-controlled trial. Participants Forty-nine methamphetamine-dependent drug users from Drug and Alcohol Services South Australia (DASSA) clinics. Intervention Participants were assigned randomly to receive up to 110 mg/day sustained-release dexamphetamine (n = 23) or placebo (n = 26) for a maximum of 12 weeks, with gradual reduction of the study medication over an additional 4 weeks. Medication was taken daily under pharmacist supervision. Measurements Primary outcome measures included treatment retention, measures of methamphetamine consumption (self-report and hair analysis), degree of methamphetamine dependence and severity of methamphetamine withdrawal. Hair samples were analysed for methamphetamine using liquid chromatography-mass spectrometry. Findings Treatment retention was significantly different between groups, with those who received dexamphetamine remaining in treatment for an average of 86.3 days compared with 48.6 days for those receiving placebo (P = 0.014). There were significant reductions in self-reported methamphetamine use between baseline and follow-up within each group (P < 0.0001), with a trend to a greater reduction among the dexamphetamine group (P = 0.086). Based on hair analysis, there was a significant decrease in methamphetamine concentration for both groups (P < 0.0001). At follow-up, degree of methamphetamine dependence was significantly lower in the dexamphetamine group (P = 0.042). Dexamphetamine maintenance was not associated with serious adverse events. Conclusions The results of this preliminary study have demonstrated that a maintenance pharmacotherapy programme of daily sustained-release amphetamine dispensing under pharmacist supervision is both feasible and safe. The increased retention in the dexamphetamine group, together with the general decreases in methamphetamine use, degree of dependence and withdrawal symptom severity, provide preliminary evidence that this may be an efficacious treatment option for methamphetamine dependence. [source] A double-blind, placebo-controlled trial of modafinil (200 mg/day) for methamphetamine dependenceADDICTION, Issue 2 2009James Shearer ABSTRACT Aim To examine the safety and efficacy of modafinil (200 mg/day) compared to placebo in the treatment of methamphetamine dependence and to examine predictors of post-treatment outcome. Participants and design Eighty methamphetamine-dependent subjects in Sydney, Australia were allocated randomly to modafinil (200 mg/day) (n = 38) or placebo (n = 42) under double-blind conditions for 10 weeks with a further 12 weeks post- treatment follow-up. Measures Comprehensive drug use data (urine specimens and self-report) and other health and psychosocial data were collected weekly during treatment and research interviews at baseline, week 10 and week 22. Results Treatment retention and medication adherence were equivalent between groups. There were no differences in methamphetamine abstinence, craving or severity of dependence. Medication-compliant subjects tended to provide more methamphetamine-negative urine samples over the 10-week treatment period (P = 0.07). Outcomes were better for methamphetamine-dependent subjects with no other substance dependence and those who accessed counselling. There were statistically significant reductions in systolic blood pressure (P = 0.03) and weight gain (P = 0.05) in modafinil-compliant subjects compared to placebo. There were no medication-related serious adverse events. Adverse events were generally mild and consistent with known pharmacological effects. Conclusions Modafinil demonstrated promise in reducing methamphetamine use in selected methamphetamine-dependent patients. The study findings support definitive trials of modafinil in larger multi-site trials. [source] Bispectral Electroencephalographic Analysis of Patients Undergoing Procedural Sedation in the Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 6 2003James R. Miner MD Abstract Objective: To determine whether there is a correlation between the level of sedation achieved during procedural sedation (PS) in the emergency department as determined by bispectral electroencephalographic (EEG) analysis (BIS) and the rate of respiratory depression (RD), the patient's perception of pain, recall of the procedure, and satisfaction. Methods: This was a prospective observational study conducted in an urban county hospital of adult patients undergoing PS using propofol, methohexital, etomidate, and the combination of fentanyl and midazolam. Consenting patients were monitored by vital signs, pulse oximetry, nasal-sample end-tidal carbon dioxide (ETCO2), and BIS monitors during PS. Respiratory depression (RD) was defined as an oxygen saturation <90%, a change from baseline ETCO2 of >10 mm Hg, or an absent ETCO2 waveform at any time during the procedure. After the procedure, patients were asked to complete three 100-mm visual analog scales (VASs) concerning their perception of pain, recall of the procedure, and satisfaction with the procedure. Patients were divided into four groups based on the lowest BIS score recorded during the procedure, group 1, >85; group 2, 70,85; group 3, 60,69; group 4, <60. Rates of RD and VAS outcomes were compared between groups using chi-square statistics. Results: One hundred eight patients were enrolled in the study. No serious adverse events were noted. RD was seen in three of 14 (21.4%) of the patients in group 1, seven of 34 (20.6%) in group 2, 16 of 26 (61.5%) in group 3, and 18 of 34 (52.9%) in group 4. The rate of RD in patients in group 2 was not significantly different from that in group 1 (p = 0.46). The rate of RD in group 2 was significantly lower than that in groups 3 (p = 0.0003) and 4 (p = 0.006). For the VAS data, when group 1 was compared with the combined groups 2, 3, and 4, it had significantly higher rates of pain (p = 0.003) and recall (p = 0.001), and a dissatisfaction rate (p = 0.085) that approached significance. When groups 2, 3, and 4 were compared with chi-square test, there was not a significant difference in pain (p = 0.151), recall (p = 0.27), or satisfaction (p = 0.25). Conclusions: Patients with a lowest recorded BIS score between 70 and 85 had the same VAS outcomes as more deeply sedated patients and the same rate of RD as less deeply sedated patients. This range of scores represented the optimally sedated patients in this study. [source] Eslicarbazepine Acetate: A Double-blind, Add-on, Placebo-controlled Exploratory Trial in Adult Patients with Partial-onset SeizuresEPILEPSIA, Issue 3 2007Christian Elger Summary:,Objective: To explore the efficacy and safety of eslicarbazepine acetate (BIA 2-093), a new antiepileptic drug, as adjunctive therapy in adult patients with partial epilepsy. Methods: A multicenter, double-blind, randomized, placebo-controlled study was conducted in 143 refractory patients aged 18,65 years with ,4 partial-onset seizures/month. The study consisted of a 12-week treatment period followed by a 1-week tapering off. Patients were randomly assigned to one of three groups: treatment with eslicarbazepine acetate once daily (QD, n = 50), twice daily (BID, n = 46), or placebo (PL, n = 47). The daily dose was titrated from 400 mg to 800 mg and to 1,200 mg at 4-week intervals. The proportion of responders (patients with a ,50% seizure reduction) was the primary end point. Results: The percentage of responders versus baseline showed a statistically significant difference between QD and PL groups (54% vs. 28%; 90% CI =,,, ,14; p = 0.008). The difference between the BID (41%) and PL did not reach statistical significance (90% CI =,,, ,1; p = 0.12). A significantly higher proportion of responders in weeks 5,8 was found in the QD group than in the BID group (58% vs. 33%, respectively, p = 0.022). At the end of the 12-week treatment, the number of seizure-free patients in the QD and BID groups was 24%, which was significantly different from the PL group. The incidence of adverse events was similar between the treatment groups and no drug-related serious adverse events occurred. Conclusion: Eslicarbazepine acetate was efficacious and well tolerated as an adjunctive therapy of refractory epileptic patients. [source] Safety and efficacy of transdermal fentanyl in patients with cancer pain: phase IV, Turkish oncology group trialEUROPEAN JOURNAL OF CANCER CARE, Issue 1 2007. KÖMÜRCÜ md We have performed a prospective evaluation of the efficacy, safety and convenience of the transdermal therapeutic system , fentanyl (TTS-F) in Turkish cancer patients when it was newly available in Turkey. Ninety-nine patients with historically confirmed malignancy and pain entered the study; the mean age was 55.1 (16,58) years. The study duration was 28 days. Transdermal therapeutic system , fentanyl was used in opioid-naïve or pre-treated patients. Most patients reported a decrease in pain severity. Use of rescue medication decreased from day 4 to day 28. The majority of patients rated patch convenience of use as excellent. A total of 22.2% of patients experienced adverse events that were either probably related or very likely to be related to the study drug. The majority of the adverse events mentioned were related to the digestive system. Eighteen serious adverse events were reported by 13 patients. Six events were doubtfully related, and 12 events were not related to the study drug. Four patients died during the trial. None of these deaths was attributed to the study drug. In conclusion, the trial showed that TTS-F is easily managed, effective and will help to enable the appropriate opioid administration to patients who are suffering from cancer pain in Turkey. [source] A randomized, double-blind trial demonstrating bioequivalence of the current recombinant activated factor VII formulation and a new robust 25°C stable formulationHAEMOPHILIA, Issue 5 2007B. V. BYSTED Summary., Recombinant activated factor VIIa (rFVIIa) is a well-established treatment for bleeding episodes in patients with congenital or acquired haemophilia A or B with inhibitors to factors VIII and IX and patients with FVII deficiency. The aim of this trial was to demonstrate bioequivalence between the currently marketed (rFVIIa/NovoSeven®) and a new rFVIIa formulation (VII25) stable at up to 25°C. Furthermore, short-term safety and tolerability of VII25 and pharmacokinetics of both formulations were investigated. In this single-centre, randomized, double-blind, two-way cross-over trial, healthy male subjects received one intravenous bolus injection of rFVIIa and one of VII25, both at 90 ,g kg,1, in a randomized order 2,3 weeks apart. Mean VII25/rFVIIa ratio for area under the plasma activity-time curve from time 0 to last quantifiable activity (primary bioequivalence endpoint), was 0.93, 90% confidence interval (CI) (0.89,0.96), within the predefined bioequivalence range (0.80,1.25). Secondary pharmacokinetic parameters were comparable between formulations. No serious adverse events were observed. Six mild or moderate treatment-emergent adverse events were reported in five subjects. Coagulation-related parameter profiles were similar between rFVIIa and VII25. No clinically abnormal changes were observed for laboratory parameters and no subjects developed FVIIa antibodies. This trial demonstrated bioequivalence between the currently available rFVIIa and VII25 stable at up to 25°C. VII25's ,user-friendly' formulation removes the inconvenience of storing/transporting at 2,8°C, and as the drug substance is the same, the activity and safety established for rFVIIa is maintained. [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] Continuous infusion of factor concentrates in children with haemophilia A in comparison with bolus injectionsHAEMOPHILIA, Issue 3 2006C. BIDLINGMAIER Summary., Although the concept of continuous infusion (CI) of factor concentrates is well known, prospective paediatric data are rare. We present a prospective open-labelled non-randomized study focusing on safety, efficacy and factor VIII (FVIII) usage compared with bolus injections (BI) in children. In 43 consecutive patients (0.5,17 years; median: 9.6) undergoing different operations, CI was started with an initial FVIII-bolus of 70 IU kg,1 bodyweight, followed by a median infusion rate of 4.4 IU kg,1 h,1 (range: 2.8,9.5) dose adjusted for daily FVIII levels (target: 60,80%). No direct serious adverse events occurred; however, two out of 43 patients, both from the group of four patients with less than 20 exposure days (ED) before starting CI, developed a high-responding inhibitor. Two CI patients showed mild thrombophlebitis or rash. Infusion rates needed to achieve adequate FVIII levels were highly predictable and could be reduced because of decreasing FVIII clearance. Bleeding, requiring additional boli, was observed in eight out of 43 patients. Therapy duration and factor usage of CI were influenced by the procedure, but not by the product used or thrombophilia. Twelve of these CI patients were compared with 12 contemporary consecutive age- and procedure-matched BI patients. Compared with BI patients, CI patients saved 30% FVIII (812.9 vs. 563.2 IU kg,1, P < 0.006). We conclude that CI forms a safe and effective method for perioperative care in children and reduces factor usage. Because of the unknown risk of inhibitor development, we will use CI only in patients beyond 20 ED. [source] Topiramate Treatment of Chronic Migraine: A Randomized, Placebo-Controlled Trial of Quality of Life and Other Efficacy MeasuresHEADACHE, Issue 8 2009Stephen Silberstein MD Objective., To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double-blind, placebo-controlled, multicenter clinical trial. Background., We previously reported that topiramate 100 mg per day produced a statistically significant reduction in mean monthly migraine/migrainous and migraine headache days compared with placebo treatment and that it was safe and generally well tolerated. Methods., Variables analyzed included between-treatment group differences in percent responders, change in the mean monthly rate of total headache days and headache-free days, change in average and worst daily headache severity, change in the mean monthly use of acute headache medications, and absolute change and percent change in a headache index. Additional analyses included evaluation of changes in: the associated symptoms of photophobia, phonophobia, and nausea; Migraine-Specific Quality of Life Questionnaire scores; Migraine Disability Assessment Scale scores; and Physician's and Subjects Global Impression of Change. Results., The intent-to-treat population consisted of 306 patients (topiramate, n = 153; placebo, n = 153). Categorical responder rates of reductions in mean monthly migraine/migrainous days for topiramate- vs placebo-treated subjects were as follows: for ,25% reduction: 68.6% vs 51.6% (P = .005); ,50%: 37.3% vs 28.8% (P = .093); and ,75%: 15.0% vs 9.2% (P = .061). The decrease in mean monthly total headache days and headache-free days for topiramate vs placebo treatment was 5.8 vs 4.7 days (P = .067). Compared with placebo, topiramate treatment resulted in statistically significant mean improvements in the Role Restrictive (P = .028) and Emotional Function (P = .036) domains of the Migraine-Specific Quality of Life Questionnaire, in the worst daily severity of migraine (P = .016), severity of photophobia (P = .032), frequency of vomiting (P = .018), photophobia (P = .038), phonophobia (P = .010), unilateral pain (P = .015), pulsatile pain (P = .023), and pain worsened because of physical activity (P = .047). In addition, there were trends observed (favoring topiramate) in average daily severity of migraine (P = .077), acute headache medication use (P = .127), severity of nausea (P = .098), frequency of nausea (P = .166), the Role Preventive domain of the Migraine-Specific Quality of Life Questionnaire (P = .061), and severity of phonophobia (P = .062). Conclusions., In addition to significantly reducing mean monthly migraine/migrainous and migraine headache days, treatment of chronic migraine with topiramate was effective with regard to several traditionally important and clinically relevant secondary outcomes in migraine prevention trials. Treatment with topiramate was well tolerated and not associated with serious adverse events. [source] Divalproex Sodium Extended-Release for the Prophylaxis of Migraine Headache in Adolescents: Results of a Stand-Alone, Long-Term Open-Label Safety StudyHEADACHE, Issue 1 2009George Apostol MD Objective., The objective of this long-term open-label study in adolescents was to assess the safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches. Background., Two formulations of divalproex sodium have demonstrated efficacy in the prevention of migraine headaches in adults. However, no medications are currently approved for this indication in adolescents, and long-term safety data on agents for migraine prevention are lacking for this younger population. Therefore, the current study was conducted to assess the long-term safety and tolerability of divalproex extended-release in adolescents with migraine headaches. Methods., This was a 12-month, phase 3, open-label, multicenter study of adolescents aged 12 to 17 years with migraine headaches diagnosed by International Headache Society criteria. Divalproex sodium extended-release was initiated at 500 mg/day for 15 days then increased to 1000 mg daily, with subsequent adjustments permitted within a dosing range of 250-1000 mg daily. Study visits were conducted at days 1 and 15 and months 1, 2, 3, 6, 9, and 12. Safety was evaluated by adverse event collection, laboratory assessments, physical and neurological examinations, vital signs, electrocardiograms, the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, the Wechsler Abbreviated Scale of Intelligence, and the Behavioral Assessment Scale for Children. Efficacy was evaluated by following the number of migraine headache days reported in subjects' headache diaries over sequential 4-week intervals for the duration of the trial. Results., A total of 241 subjects were enrolled and treated. The most frequently reported adverse events were nausea (19%), vomiting (18%), weight gain (12%), nasopharyngitis (11%), migraine (10%), and upper respiratory tract infection (10%). Ten (4%) subjects experienced serious adverse events, and 40 (17%) subjects discontinued because of an adverse event. Increases in ammonia levels were observed. No other clinically significant changes were observed in laboratory values, vital signs, rating scales, or electrocardiograms. Median 4-week migraine headache days decreased 75% between the first and the fourth months of the study (from 4.0 to 1.0) and remained at or below this level for the remainder of the study. Conclusions., In this long-term open-label study of adolescents with migraine, the safety and tolerability profile of divalproex sodium extended-release was consistent with findings from previous trials in adults, as well as 2 studies recently completed in adolescents. In general, divalproex sodium extended-release was well-tolerated in adolescents with migraine. [source] Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen,positive chronic hepatitis B,HEPATOLOGY, Issue 3 2008Patrick Marcellin Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES). At enrollment, the 65 LTSES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log10 copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 × upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log10 copies/mL and ,50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow-up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A181V or N236T developed in 13 LTSES patients; the first observation was at study week 195. There were no serious adverse events related to ADV. Conclusion: Treatment with ADV beyond 48 weeks was well tolerated and produced long-term virological, biochemical, serological, and histological improvement. (HEPATOLOGY 2008;48:750,758.) [source] | ||||||||||||||||||||||||||||||||||||||||