Adverse Event

The introduction of highly active antiretroviral therapy (also known as combination therapy) has transformed the nature of HIV infection from a severe and ultimately fatal disease to that of a manageable chronic condition. HIV drugs are highly efficacious, but their use comes at ...

However, such differences between countries may be due more to differences in the medical systems rather than differences in the quality of patient care. The United States has a very different medical environment, partly because of the highly litigious nature of US culture. 2 The fear of being sued may reduce the incidence of hindsight bias3 in US studies, since physicians may order more tests than are strictly necessary, which makes it more difficult for researchers such as Baker and associates to second-guess their decisions.

To define a safe and effective dose of Dysport for treating hip adductor spasticity. Patients with definite or probable multiple sclerosis, and disabling spasticity affecting the hip adductor muscles of both legs, were randomised to one of four treatment groups. Dysport (500, 1000, or 1500 Units), or placebo was administered by intramuscular injection to these muscles. Patients were assessed at entry, and 2, 4 (primary analysis time-point), 8, and 12 weeks post-treatment. A total of 74 patients were recruited. Treatment groups were generally well matched at entry. The primary efficacy variables-passive hip abduction and distance between the knees-improved for all groups. The improvement in distance between the knees for the 1500 Unit group was significantly greater than placebo (p = 0.02). Spasm frequency was reduced in all groups, but muscle tone was reduced in the Dysport groups only. Pain was reduced in all groups, but improvements in hygiene scores were evident only in the 1000 ...

Children with hyperlipidemia secondary to renal disease develop premature atherosclerosis and glomerulosclerosis. The aims of this pilot study were to find the dosage and short-term efficacy of simvastatin and potential adverse events in children with chronic kidney diseases. This was a random, double-blind, placebo-controlled, cross-over clinical trial performed on children with hyperlipidemia secondary to kidney disorders. After being placed on a diet for 3 months, patients were randomly placed in one of two balanced group blocks and treated with diet plus placebo or simvastatin at doses of 5 mg for children weighing 30 kg or less and 10 mg for children weighing over 30 kg, for 1 month, and then doubled for two more months. After this treatment, patients were placed on a diet for a 3-month washout period. During the last trial phase, patients previously treated with simvastatin were administered a placebo, and vice versa. A total of 25 patients with ages ranging from 4 years to 17 years were included in the study. A significant decrease in the levels of serum cholesterol (26.4%), low-density lipoprotein (LDL) (35.4%) and triglycerides (23.1%) was noted during the study, primarily during the simvastatin treatments, in which case cholesterol, LDL and triglycerides decreased by 23.3%, 33.7% and 21%, respectively. High-density lipoprotein (HDL) levels increased moderately (10.7%) during the study but without differences during simvastatin treatment. No differences were found across groups with respect to adverse events. In the short-term the combination of diet and simvastatin was effective in lowering hyperlipidemia in children with renal disorders.

Background: This is the first prospective, randomized, double-blind, placebo-controlled study showing statistical improvement of an H1-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. Objective: This randomized, placebo-controlled, parallel-group, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. Methods: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (±1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point. Results: Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P ≤ .0001). Individual symptom scores showed statistically significant superiority compared with placebo (P < .05), including nasal congestion in the evening reflective assessment (P < .05). There was no significant difference in adverse events between fexofenadine and placebo, either overall or by causality. Conclusion: The efficacy and safety of the H1-antihistamine fexofenadine has been confirmed in this multicenter, multinational study of children aged 6 to 11 years with seasonal allergic rhinitis.

Results: No infusion was interrupted for symptoms, although 5 of 24 subjects had mild infusion-day adverse events thought to be possibly drug-related. No subject developed anti-FG-3019 antibodies. FG-3019 clearance was lower at 10 mg/kg than at 3 mg/kg, ...

Background The ACT recommended by WHO is very effective and well-tolerated. However, these combinations need to be administered for three days, which may limit adherence to treatment. The combination of dihydroartemisinin - piperaquine phosphate - trimethoprim (Artecom®, Odypharm Ltd), which involves treatment over two days, appears to be a good alternative, particularly in malaria-endemic areas. This study intends to compare the efficacy and tolerability of the combination dihydroartemisinin - piperaquine phosphate - trimethoprim (DPT) versus artemether - lumefantrine (AL) in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroon, Ivory Coast and Senegal. Methods This was a randomized, controlled, open-label clinical trial with a 28-day follow-up period comparing DPT to AL as the reference drug. The study involved patients of at least two years of age, suffering from acute, uncomplicated Plasmodium falciparum malaria with fever. The WHO 2003 protocol was used. Results A total of 418 patients were included in the study and divided into two treatment groups: 212 in the DPT group and 206 in the AL group. The data analysis involved the 403 subjects who correctly followed the protocol (per protocol analysis), i.e. 206 (51.1%) in the DPT group and 197 (48.9%) in the AL group. The recovery rate at D14 was 100% in both treatment groups. The recovery rate at D28 was 99% in the DPT and AL groups before and after PCR results with one-sided 97.5% Confidence Interval of the rates difference > -1.90%. More than 96% of patients who received DPT were apyrexial 48 hours after treatment compared to 83.5% in the AL group (p < 0.001). More than 95% of the people in the DPT group had a parasite clearance time of 48 hours or less compared to approximately 90% in the AL group (p = 0.023). Both drugs were well tolerated. No serious adverse events were reported during the follow-up period. All of the adverse events observed were minor and did not result in the treatment being stopped in either treatment group. The main minor adverse events reported were vomiting, abdominal pain and pruritus. Conclusion The overall efficacy and tolerability of DPT are similar to those of AL. The ease of taking DPT and its short treatment course (two days) may help to improve adherence to treatment. Taken together, these findings make this medicinal product a treatment of choice for the effective management of malaria in Africa.

There are few data on plasma and intracellular pharmacokinetics (PK) of once-daily (q24h) nucleoside analogues in HIV-infected children. Children aged 2-13 years receiving combination treatment containing lamivudine (3TC) (4 mg/kg) and/or abacavir (ABC) (8 mg/kg) twice daily (q12h) were included in this single-arm, open-label, crossover study. Intensive plasma PK sampling was performed at steady state, after which children switched to q24h dosing and PK sampling was repeated 4 weeks later. Daily area under the curve (AUC0-24) and peak level (Cmax) of q24h and q12h regimens were compared by geometric mean ratios (GMRs) with 90% confidence intervals (CIs). Children were followed for 24 weeks to evaluate safety and virological response. 24 children were enrolled, of whom 20 [median age (range) 5.6 (2.1-12.8) years] had evaluable PK data for 3TC (n=19) and/or ABC (n=14). GMRs of 3TC and ABC AUC0-24 and Cmax q24h versus q12h significantly exceeded 1.0. GMRs were not significantly differe...

While evidenced-based guidelines promote glycated hemoglobin (HbA(1c)) targets &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;7.0% in order to reduce the long-term risk of diabetic complications, many individuals with type 2 diabetes do not achieve these targets. Fear of hypoglycemia provides a major barrier to improving blood glucose control as a result of delayed insulin initiation and failure to appropriately titrate insulin following initiation. Modern insulin analogs were designed to achieve improved blood glucose control with similar hypoglycemic risk compared with non-analog insulins (or similar blood glucose control with reduced hypoglycemic risk). While this has been demonstrated in randomized controlled trials, there is a need to confirm these findings in an everyday clinical setting. The A(1)chieve study will evaluate adverse events and effectiveness of premix (biphasic insulin aspart 30 [NovoMix 30]), basal (insulin detemir [Levemir]), and meal-time (insulin aspart [NovoRapid]) insulin analogs in people with type 2 diabetes in near-routine clinical practice. A(1)chieve is an international, prospective, multi-center, open-label, non-interventional, 24-week study of people with type 2 diabetes using an insulin analog. The study will recruit 60 000 people from 30 countries across four continents (Asia, Africa, South America, and Europe). The primary aim of the study is to assess the adverse event profile of the study insulins in routine clinical practice, including rates of hypoglycemia. In addition, effectiveness (HbA(1c), fasting plasma glucose, and postprandial plasma glucose) and patient quality of life outcomes will be measured. Comprehensive epidemiological data will be collected at baseline, including recent plasma glucose results and hypoglycemic episodes, prevalence of diabetes-related complications, and measures of current standards of care. Thus, A(1)chieve should provide important information about how insulin analogs perform in daily clinical practice.

Aim  Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without anaesthesia.Design  Randomized controlled open clinical trial from September 1999 to August 2001.Setting  Four addiction centres in collaboration with three general hospitals in the Netherlands.Participants  A total of 272 opioid-dependent patients whose previous attempts to abstain were unsuccessful.Intervention  Patients received rapid detoxification with general anaesthesia (RD-GA) or without general anaesthesia (RD).Measurements  Urine screens and an interview (EuropASI) to assess opioid abstinence; two questionnaires (SOOS, OOWS) to measure withdrawal symptoms and one to measure craving (VAS).Findings  One month after the intervention 62.8% of the patients in the RD-GA group and 60.0% in the RD group were abstinent for opioids (P = 0.71). No adverse events or complications occurred during RD; however, in the RD-GA group, five adverse events necessitated admission to a general hospital. The average 1-month cost for RD was €2517 versus €4439 for RD-GA.Conclusions  Rapid detoxification under general anaesthesia did not result in higher levels of opioid abstinence than rapid detoxification without anaesthesia. The cost of the former intervention was much higher.

Previous small phase II trials have demonstrated that the combination of 5-fluorouracil (5FU) and cisplatin(CDDP) could have clinical activity in metastatic biliary tract cancer. This randomised phase II trial was designed to assess the activity and safety of a high-dose infusional weekly 5FU alone (HDFU) and the combination of 5FU, folinic acid (FA) and CDDP. Patients were included if they had histologically proven locally advanced or metastatic biliary tract carcinoma, World Health Organisation (WHO) performance status &amp;lt; or = 2, bilirubin &amp;lt;2 x upper normal limit, adequate haematological and renal functions and had not received prior chemotherapy, even in the adjuvant setting. Arm A (HDFU) consisted of cycles of 5FU 3 g/m(2) intravenously (i.v.), 24 h infusion, weekly, for 6 weeks, followed by 1 week rest, every 7 weeks; Arm B (5FU+FA+CDDP) consisted of cycles of 5FU 2.0 g/m(2) i.v. with folinic acid 500 mg/m(2), 2 h-infusion, weekly, for 6 weeks, followed by 1 week rest plus cisplatin 50 mg/m(2), once every two weeks, for 6 weeks, followed by 1 week rest, every 7 weeks. From February 1997 to June 1999, 58 patients were randomised (29 in each arm). Patients had a median age of 58 years in Arm A and 62 years in Arm B, locally advanced disease was present in 21% of the patients in Arm A and 11% in Arm B. WHO performance status of 0/1/2 was noted in 48%/45%/7% of the patients in Arm A and 54%/43%/4% in Arm B. In both arms, the most common metastatic sites were the liver and peritoneum. Twenty-eight patients were eligible in each arm and one patient did not start the allocated therapy in Arm B. The median number of cycles was 2 [range 1-12] in Arm A and 2 [range 1-6] in Arm B. Responses for the eligible patients who started their allocated therapy were as follows: Complete Response (CR) 0% in Arm A, 4% in Arm B, Partial Response (PR) 7% in Arm A, 15% in Arm B resulting in an overall response rate [95% CI] of 7.1% in Arm A [0.9-23.5%] and 19% [6.3-38.1%] in Arm B. Disease stabilisation was observed in 46% in Arm A and 44% in Arm B. National Cancer Institute of Canada (NCIC) grade 3-4 adverse events (% of patients in Arm A/Arm B) were neutropenia 4%/26%, thrombopenia 0%/7%, stomatitis 0%/4%, vomiting 7%/14%, diarrhoea 0%/11% and neurotoxicity 4%/0%. There was one early toxic death in Arm B. The median overall survival (OS) [95% CI] was in Arm A/Arm B: 5.0 [4.0-7.4] months/8.0 [5.8-11.8] months and the median progression-free survival (PFS) was 3.3 [1.7-4.7] months/3.3 [2.3-6.7] months. Cisplatin in combination with 5FU+FA showed a higher activity than HDFU, but was more toxic. These results are not sufficient to start a phase III trial. However, our group is planning a phase III trial comparing 5FU+folinic acid versus the same schedule+oxaliplatin a platinum analogue.