Randomized clinical trial: effect of the 5-HT4 receptor agonist revexepride on reflux parameters in patients with persistent reflux symptoms despite PPI treatment.

BACKGROUND: Approximately, 20-30% of patients with gastro-esophageal reflux disease (GERD) experience persistent symptoms despite treatment with proton pump inhibitors (PPIs). These patients may have underlying dysmotility; therefore, targeting gastric motor dysfunction in addition to acid inhibition may represent a new therapeutic avenue. The aim of this study was to assess the pharmacodynamic effect of the prokinetic agent revexepride (a 5-HT4 receptor agonist) in patients with GERD who have persistent symptoms despite treatment with a PPI. METHODS: This was a phase II, exploratory, multicenter, randomized, placebo-controlled, double-blind, parallel-group study in patients with GERD who experienced persistent symptoms while taking a stable dose of PPIs (ClinicalTrials.gov identifier: NCT01370863). Patients were randomized to either revexepride (0.5 mg, three times daily) or matching placebo for 4 weeks. Reflux events and associated characteristics were assessed by pH/impedance monitoring and disease symptoms were assessed using electronic diaries and questionnaires. KEY RESULTS: In total, 67 patients were enrolled in the study. There were no significant differences between study arms in the number, the mean proximal extent or the bolus clearance times of liquid-containing reflux events. Changes from baseline in the number of heartburn, regurgitation, and other symptom events were minimal for each treatment group and no clear trends were observed. CONCLUSIONS & INFERENCES: No clear differences were seen in reflux parameters between the placebo and revexepride groups.

Iontophoretic transdermal system using fentanyl compared with patient-controlled intravenous analgesia using morphine for postoperative pain management.

BACKGROUND: The fentanyl iontophoretic transdermal system (fentanyl ITS) enables needle-free, patient-controlled analgesia for postoperative pain management. This study compared the efficacy, safety, and ease of care of fentanyl ITS with patient-controlled, i.v. analgesia (PCIA) with morphine for postoperative pain management. METHODS: A prospective, randomized, multicentre trial enrolled patients in Europe after abdominal or orthopaedic surgery. Patients received fentanyl ITS (n = 325; 40.0 microg fentanyl over 10 min) or morphine PCIA [n = 335; bolus doses (standard at each hospital)] for < or =72 h. Supplemental i.v. morphine was available during the first 3 h. The primary efficacy measure was the patient global assessment (PGA) of the pain control method during the first 24 h. RESULTS: PGA ratings of 'good' or 'excellent' were reported by 86.2 and 87.5% of patients using fentanyl ITS or morphine PCIA, respectively (95% CI, -6.5 to 3.9%). Mean (sd) last pain intensity scores (numerical rating scale, 0-10) were 1.8 (1.77) and 1.9 (1.86) in the fentanyl ITS and morphine PCIA groups, respectively (95% CI, -0.38 to 0.18). More patients reported a system-related problem for fentanyl ITS than morphine PCIA (51.1 vs 17.9%, respectively). However, fewer of these problems interrupted pain control (4.4 vs 41.3%, respectively). Patients, nurses, and physiotherapists reported more favourable overall ease-of-care ratings for fentanyl ITS than morphine PCIA. Study termination rates and opioid-related side-effects were similar between groups. CONCLUSION: Fentanyl ITS and morphine PCIA were comparably effective and safe.

Meniett therapy: rescue treatment in severe drug-resistant Ménière's disease?

CONCLUSION: Our data indicate that Meniett therapy is unlikely to be helpful in the long-term treatment of patients with severe, drug-resistant Ménière's disease (MD) in whom injection of intratympanic gentamicin (ITG) or another destructive procedure would otherwise be performed. OBJECTIVE: To investigate the value of Meniett therapy in patients with drug-resistant MD referred for injection of ITG. MATERIAL AND METHODS: Twelve patients referred for ITG treatment were followed during a 2-month period of Meniett therapy. Symptoms, functional level and hearing status were evaluated using a standardized staging system. Disease-specific quality-of-life measures were obtained before and after Meniett therapy. At the end of the study period, patients were followed for a mean of 37 months, thus providing long-term outcome data. RESULTS: In two patients, Meniett treatment was interrupted after 1 month because of persistent severe vertigo. In the remaining 10 subjects, we found a significant decrease in the median number of vertigo spells from 10.0/month (25th-75th percentile 4.0-19.0) prior to treatment to 3.0/month (25th-75th percentile 1.5-4.5) after treatment (p = 0.02). There was, however, no improvement in hearing status, tinnitus, functional level or self-perceived dizziness handicap. Long-term (>1 year) follow-up data revealed that only 2 subjects preferred to continue Meniett therapy and that ablative surgery had to be performed in 6/12 study patients.

Otolith function after acoustic neuroma surgery.

The response of the vestibular system after acoustic neuroma surgery was investigated in nine patients. The otolith system was studied by means of ocular counterrolling, assessed by video oculography. Horizontal vestibulo-ocular reflex (VOR) function was tested by the sinusoidal harmonic acceleration test using electronystagmography. The results were compared with those obtained from a normal control population. The response to slow rotation tests was symmetric, but the gain was significantly reduced when compared to the normal population. Phase lag was significantly increased. No difference in ocular torsion was observed with lateroflexion of the head to the ipsilateral side in comparison with lateroflexion to the contralateral side. Moreover, the overall ocular counterrolling was well within normal limits. We conclude that the semicircular canal response differs from the otolith response. The component of the torsional VOR mediated by otolith stimulation appears to be more robust than the horizontal VOR mediated mainly by the horizontal semicircular canal system. Ocular counterrolling induced by lateroflexion does not reveal abnormalities in patients with surgically produced unilateral peripheral loss.

Ketoconazole 2% emulsion in the treatment of seborrheic dermatitis.

Fifty patients (42 men, 8 women) with seborrheic dermatitis were included in the trial. Ketoconazole 2% emulsion or the same emulsion without active drug was applied b.i.d. for 4 weeks. Two patients dropped out in the ketoconazole group and nine in the placebo group. Pityrosporum ovale was cultured from all patients at the start and from six out of 23 in the ketoconazole group versus nine out of 16 in the placebo group at week 4. The overall assessment showed a significantly better response to treatment for the ketoconazole emulsion (72%) than for the placebo (32%).

Digital blood pressure and flow measurements in patients with primary Raynaud's phenomenon.

The value of digital systolic blood pressure (DBP) and flow (DBF) measurements for a quantitative diagnosis of Primary Raynaud's Phenomenon (PRP) was evaluated by comparing the results obtained in 10 patients and 20 normals. Digital skin temperature (DST), DBP and brachial systolic blood pressure (BBP) and DBF were measured at room temperature, at maximal vasodilatation and during cold provocation. At room temperature DST discriminates between normals and patients with an accuracy of 77%. On maximum vasodilatation no significant differences can be found in DBP and DBF between normals and patients. However, DBF was significantly different between male and females both in normals and in patients. During gradual cooling a decrease in DBF (a closing phenomenon) was observed both in normals and patients. In contrast DBP did not show a substantial pressure drop. Calculating digit to brachial systolic pressure indexes (DBI) a slight significant increase can be found during cold provocation both in normals and in patients. Only the DBI of digit IV during cold provocation showed a significant difference between normals and patients which resulted in an accuracy of 83%.

The influence of ritanserin, a serotonin antagonist, in anxiety disorders: a double-blind placebo-controlled study versus lorazepam.

A double-blind study was performed in 83 patients with generalized anxiety disorder comparing daily doses of 5 and 10 mg ritanserin (a selective antagonist of serotonine S2 receptors) versus placebo and 4 mg lorazepam as reference drug. Patients treated with 10 mg ritanserin or 4 mg lorazepam improved significantly better (p less than 0.05) after two weeks than those treated with placebo. On the other hand a daily dose of 5 mg ritanserin appeared to be not superior to placebo. Patients treated with 4 mg lorazepam complained significantly more about sedation and dizziness than patients treated with 10 mg ritanserin (p less than 0.05).

Effect of serotonin antagonism in schizophrenia: a pilot study with setoperone.

The new antipsychotic drug setoperone is pharmacologically characterized by its potent serotonin and moderate dopamine receptor blocking properties. Forty chronic schizophrenic patients were included and 34 completed this pilot study. Following a drug-free period of 1 week the patients received setoperone 5 mg t.i.d. After 1 month of treatment, the psychotic symptoms, as measured by the BPRS, improved by approximately 50% (P less than 0.001) as compared with the condition under previous neuroleptic medication. Blockade of serotonin receptors may be related to improvement of autistic behaviour, dysphoria, and parkinson-like symptoms. In residual schizophrenic patients, the need for dopamine blockade, which is normally correlated with the therapeutic effect on positive symptoms, can be reduced substantially.