Once-Daily Oral Levofloxacin Monotherapy versus Piperacillin/Tazobactam Three Times a Day: A Randomized Controlled Multicenter Trial in Patients with Febrile Neutropenia

A prospective, randomized, controlled multicenter trial was performed to evaluate the efficacy and safety of once-daily oral monotherapy with 500 mg levofloxacin in comparison with 4.5 g piperacillin/tazobactam 3 times a day in patients with low-risk febrile neutropenia. Low risk was defined by oral temperature > or = 38.5 degrees C on one occasion or > or = 38.0 degrees C twice within 24 hours and granulocytopenia < or = 500/microL for less than 10 days. The primary end point was defined as defervescence after 72 hours followed by at least 7 afebrile days. Secondary end points were overall response, time to defervescence, survival on day 30, and toxicity. Thirty-four episodes were included. Fever of unknown origin accounted for 26 (76.5%) of the episodes, microbiologically defined infection for 5 (14.7%) of the episodes, and clinically defined infection for 3 (8.8%) of the episodes. On an intent-to-treat basis, all episodes were evaluable for the primary end point. Levofloxacin and piperacillin/tazobactam were successful after 72 hours of treatment in 76.5% and 88.3% of the episodes. Overall response was achieved in 94.1% and 100% of the episodes, respectively. One inpatient in the oral treatment group died of septic shock without identification of a causative pathogen. A larger phase III trial is warranted to further evaluate the lack of inferiority of the oral monotherapy regimen versus standard intravenous therapy.     

Iron chelation in thalassemia: combined or monotherapy? The Egyptian experience

Patients with thalassemia major requiring regular blood transfusions accumulate iron that is toxic to the heart, liver, and endocrine systems. The following prospective, randomized trial was carried out to determine the effectiveness, in children and young adults, of combined deferiprone (DFP) and deferoxamine (DFO) in reducing transfusional iron overload compared to either drug alone and to assess the safety and tolerability of DFP. Sixty-six patients were randomized into three treatment arms: daily DFP combined with DFO twice weekly; daily DFP only; and DFO only 5 days/week. Fifty-six patients completed the 54 weeks and were assessed by different indices. A significant reduction of liver iron concentration and serum ferritin was observed in all three arms while significant reduction of liver iron score was observed in patients on combination therapy only. Cardiac function did not significantly change in any arm. Compliance improved in patients who received combined therapy. Toxicity of DFP was mild to moderate and acceptable; most commonly, transient arthropathy and nausea/vomiting were observed. Thus, combination therapy has shown to be effective in reducing iron overload in thalassemia patients.     

Efficacy and safety of certolizumab pegol without methotrexate co-administration in Japanese patients with active rheumatoid arthritis: The HIKARI randomized,placebo-controlled trial

Abstract

Objective. This 24-week, placebo-controlled, double-blind, randomized study (NCT00791921) investigated efficacy and safety of certolizumab pegol (CZP) in Japanese rheumatoid arthritis (RA) patients in whom methotrexate (MTX) cannot be administered.

Methods. A total of 230 patients were randomized to subcutaneous CZP 200 mg (induction dosing: 400 mg at Weeks 0, 2 and 4) or placebo every 2 weeks.

Results. ACR20 responses with CZP were rapid and significant versus placebo at Week 1, sustained to Week 12 (67.2% vs. 14.9%) and Week 24 (63.8% vs. 11.4%). Week 24-modified Total Sharp Score (mTSS) change from baseline (CFB) was 0.48 (CZP) versus 2.45 (placebo). CZP treatment was associated with higher Week 12 ACR20 responses versus placebo (with non-MTX disease modifying antirheumatic drugs [DMARDs], 74.2% vs. 20.0%; without [monotherapy], 59.3% vs. 8.2%) and inhibition of radiographic progression at Week 24 (mTSS CFB; with non-MTX DMARDs, 0.24 vs. 1.61; monotherapy, 0.68 vs. 3.65). Incidences of serious adverse events were 11.2% (CZP) and 2.6% (placebo); one CZP patient died of dissecting aortic aneurysm.

Conclusion. CZP treatment with and without non-MTX DMARDs in Japanese patients in whom MTX cannot be administered resulted in rapid, sustained reductions in RA signs and symptoms. Notably, CZP monotherapy showed significant inhibition of radiographic progression.     

Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients who could not receive methotrexate: 52-week results from an open-label extension of the HIKARI study

Abstract

Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients who could not receive methotrexate (MTX).

Methods. HIKARI double-blind (DB) patients were entered into an open-label extension (OLE) study. Patients withdrawn at 16 weeks due to lack of efficacy and DB completers without a 24-week American College of Rheumatology (ACR)20 response received CZP 200 mg every 2 weeks (Q2W). DB completers with 24-week ACR20 responses were randomized to CZP 200 mg Q2W or CZP 400 mg every 4 weeks.

Results. The ACR20/ACR50/ACR70 response rates of DB completers (n = 98) were 82.7%/56.1%/34.7% at OLE entry, and 83.7%/65.3%/48.0% at 52 weeks, respectively. Other clinical, functional, and radiographic outcomes were sustained during long-term administration of CZP, even without MTX. No new unexpected adverse events were observed during long-term CZP treatment. The efficacy and safety of CZP treatment were similar between the two dosing schedules.

Conclusions. Long-term CZP administration is efficacious and safe for RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules. The choice between two maintenace regimens adds flexibility in administration schedules for RA patients and physicians.     

Effects of acute low-dose combined treatment with naloxone and AM 251 on food intake, feeding behaviour and weight gain in rats

Low-dose combinations of naloxone and rimonabant produce additive effects on food intake and feeding behaviour, yet abolish the scratching syndrome typically induced by rimonabant per se. To assess the generality of these findings, we have examined the acute effects of low-dose combinations of naloxone (0.1 mg/kg) and the rimonabant derivative AM 251 (0.5 and 1.0 mg/kg) on food intake, feeding behaviour and weight gain in non-deprived male rats. Although ineffective when given alone, combined treatment with naloxone and 0.5 mg/kg AM 251 significantly and selectively suppressed mash intake and time spent feeding. By itself, 1.0 mg/kg AM 251 failed to alter any measure of feeding behaviour but did reduce food consumption and induce scratching behaviour. Co-administration of naloxone with 1.0 mg/kg AM 251 not only significantly suppressed both food intake and feeding behaviour but also simultaneously attenuated AM 251-induced scratching. This profile mirrors earlier findings with naloxone/rimonabant and is consistent with the reported diversity of opioid-cannabinoid system interactions at a more molecular level. Although further studies are required (e.g. ‘neutral’ CB1 receptor antagonists), current data constitute further proof of concept regarding the anorectic efficacy, selectivity and added value of low-dose polytherapy with opioid and CB1 receptor antagonists.     

A long-term follow-up of zonisamide monotherapy

OBJECTIVES: Several studies have reported the safety and efficacy of zonisamide monotherapy, but studies on its long-term outcomes are limited. This chart review was conducted to evaluate the long-term outcomes of zonisamide monotherapy. METHODS: The charts were reviewed for 77 patients treated with zonisamide as monotherapy for 6-180 months between May 1985 and December 2003. Outcomes were analyzed by the following subcategories: patients with newly diagnosed epilepsy or with antiepileptic drug-resistant epilepsy, the type of epilepsy, patient age, and treatment period. RESULTS: Of a total of 77 patients, 49 patients (64%) attained 50% or more reduction of seizure frequency and of those patients 38 (49%) attained 75% or more reduction, with 18 patients (24%) becoming seizure-free from 6 to 180 (median 80.6 +/- 43.6) months of follow-up. Thirty-eight patients (49%) continued zonisamide monotherapy as of December 2003. Proportions of patients having 75% or more reduction in seizure frequency in subcategories were as follows; 56% in patients with newly diagnosed epilepsy and 48% in patients whose treatment was switched to zonisamide monotherapy owing to lack of efficacy of or adverse reaction to previous antiepileptic drugs; 60% in patients with localization-related epilepsies and 38% in patients with generalized epilepsies; and 49% in pediatric patients and 50% in adult patients. CONCLUSION: Long-term zonisamide monotherapy was efficacious in a wide range of patients with epilepsy. Zonisamide did not seem to exhibit a reduction in efficacy during long-term use of up to 180 months.     

Effect of antiepileptic drug monotherapy on urinary pH in children and young adults

Objects Since alkaline urine is a risk factor for urolithiasis, the relationship between antiepileptic drugs and urinary pH was retrospectively studied in epilepsy patients treated with antiepileptic drug monotherapy for more than 1 month.Methods A total of 913 urinary samples from antiepileptic drug-treated patients were compared with 780 age-matched control samples, and with 112 samples from epilepsy patients who had not been treated with antiepileptic drugs. The antiepileptic drugs administered were carbamazepine, valproate, phenobarbital, zonisamide, sulthiame, and phenytoin.Conclusions The proportion of the acid urine in the valproate-treated patients was lower than that in controls. The proportion of the alkaline urine in the valproate-treated patients was higher than that in controls. This effect was independent of age, sex, and the serum valproate concentration. There was no significant difference in urinary pH among the epilepsy patients treated with other antiepileptic drugs, the epilepsy patients who had not been treated with antiepileptic drugs, and the controls.     

Topiramate in older patients with partial-onset seizures: a pilot double-blind, dose-comparison study

Purpose: Pharmacokinetics of antiepileptic drugs (AEDs) can be altered by age-related changes in physiology, thereby altering clinical effects, especially tolerability, in older adults. We compared two dosages of topiramate (TPM) in a pilot study of patients ≥60 years of age with partial-onset seizures.
Methods: In this 24-week, double-blind, randomized, parallel-group study, patients with one or more seizures in previous 6 months were randomized to treatment with 50 or 200 mg/day TPM. TPM was initiated as monotherapy or added to one AED and titrated by 25 mg/day per week to target or maximum tolerated dose as the concomitant AED, if any, was withdrawn.
Results: Thirty-eight patients were randomized to the 50 mg/day TPM (mean age, 68 years) and 39–200 mg/day TPM (69 years). Seizure control was similar with the two dosages when TPM could be used as monotherapy, whereas 200 mg TPM was more effective than 50 mg in patients requiring adjunctive therapy. The overall incidence of adverse events was similar for the two dosages—66% with 50 mg and 62% with 200 mg TPM. Most common adverse events were somnolence (TPM 50, 13%; TPM 200, 8%), dizziness (13% vs. 8%), and headache (13% vs. 5%). Of 10 (13%) patients reporting a cognitive-related adverse event, six patients were assigned to the 50-mg group. A total of 14 patients (18%; seven in each group) discontinued TPM due to adverse events.
Conclusions: This pilot study supports the practice of using low-to-moderate dosages of AEDs in older adults.     

Long-Term Efficacy and Safety of Zonisamide Monotherapy in Epilepsy Patients

Background and purpose

Zonisamide (ZNS) is a useful antiepileptic drug with a broad therapeutic spectrum. However, there is limited information on the long-term use of ZNS as a monotherapy. This study investigated the long-term effects of ZNS as a monotherapy for the treatment of epilepsy.

Methods

We retrospectively analyzed the records of epilepsy patients treated with ZNS monotherapy at our clinic. We identified outcomes for patients treated with ZNS monotherapy for a minimum of 6 months. Efficacy was quantified as the percentage change in seizure frequency, and safety was assessed by the frequency and types of adverse events.

Results

Sixty patients who received ZNS for a minimum of 6 months were included. The mean duration of treatment was 19.8 months (range, 6-37 months), and the mean ZNS dosage was 255 mg/day (range, 100-500 mg/day). Twenty-seven patients (45%) were seizure-free, and an additional 20 patients (33%) had above 50% seizure frequency reduction at the last follow-up visit. Partial seizures with or without secondary generalization and generalized seizures were well controlled by ZNS, whereas complex partial seizures were not. Forty-eight patients (80%) reported mild-to-moderate adverse events, including memory loss (35%), attention deficit (27%), and weight loss (20%).

Conclusions

Long-term ZNS monotherapy is effective at treating a broad spectrum of seizure disorders, except complex partial seizures. However, a specific adverse event, such as cognitive impairment, is common and long-lasting.