Comparison of twice-daily and four-times daily administration of beclomethasone dipropionate in patients with severe chronic bronchial asthma

Summary Twice-daily and four-times daily treatment with beclomethasone dipropionate aerosol were compared in a double dummy crossover study in patients with severe chronic bronchial asthma. The trial consisted of two two-month treatment periods preceded by a two-week baseline period. No significant difference was found in the morning or evening PEF, in symptom scores for wheeze, cough, sputum, sleep disturbance, limitation of daily activity, rhinitis, daily usage of bronchodilator aerosol or requirement for additional oral corticosteroids. The study has confirmed that in management of severe bronchial asthma, a twice-daily regimen of beclomethasone dipropionate aerosol is as effective as four-times daily treatment, if the total daily dose of beclomethasone dipropionate is kept unchanged.     

Comparison of analgesic efficacy of oxycodone and morphine in postoperative intravenous patient-controlled analgesia

Background : Morphine has been the standard opioid in patient-controlled analgesia (PCA). Oxycodone, the analgesic potency of which in i.v. administration has been suggested to be slightly greater than that of morphine, has not yet been studied for its efficacy in PCA.
Methods : Fifty patients, undergoing a plastic reconstruction of the breast or a major operation of the vertebrae, such as lumbar spinal fusion, used PCA for postoperative pain. Patients were randomized to receive either morphine 45 μg/kg or oxycodone 30 μg/kg as i.v. bolus doses. Patients were assessed for pain with a visual analogue scale (VAS) and side effects at 3, 9 and 24 h. Venous blood samples for the measurement of plasma concentration of oxycodone and that of morphine and its metabolites were taken.
Results : In this study patients needed, on average, the same amount of oxycodone and morphine in the recovery room and on the ward. There was no difference in the quality of analgesia (VAS) or incidence of side effects, such as nausea, vomiting, pruritus and urinary retention. The plasma concentrations of morphine-6-glucuronide showed that this metabolite might contribute to the analgesia resulting from morphine administration.
Conclusions : The same dose of intravenous oxycodone and morphine administered by PCA pump was needed for immediate postoperative analgesia. The two drugs appear to be equipotent.     

Safety,tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid-treated asthmatic patients

The purpose of this randomized, double-blind parallel group study was to compare the safety, tolerability and acceptability of Easyhaler and Turbuhaler dry powder inhalers for the delivery of budesonide 800 microg day(-1) in adult asthmatic patients who had already been treated with inhaled corticosteroids for at least 6 months prior to the study Additionally the efficacy of the products was evaluated. The main objective was to evaluate the systemic safety of budesonide inhaled from Easyhaler (Giona Easyhaler, Orion Pharma, Finland) as determined by serum and urine cortisol measurements. The secondary objective was to compare the tolerability acceptability and efficacy of the two devices in the administration of budesonide. After a 2-week run-in period (baseline), patients were randomized on a 2:1 basis to receive budesonide from Easyhaler (n = 103) or from Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Sweden) (n = 58) 200 g dose(-1), two inhalations twice daily for 12 weeks.There was no statistically significant change in morning serum cortisol values from baseline to the end of treatment in either group.Urine free cortisol and urine cortisol/ creatinine ratio increased from baseline in both groups. There were no significant differences between the groups in terms of morning serum cortisol, urine cortisol, adverse events or efficacy variables, but Easyhaler was generally considered more acceptable to the patients. In conclusion, at 800 microg day(-1), Giona Easyhaler is as safe and efficacious as Pulmicort Turbuhaler in adult asthmatic patients previously treated with corticosteroids, but more acceptable to patients.     

Factors predicting chronic pain after open inguinal hernia repair: a regression analysis of randomized trial comparing three different meshes with three fixation methods (FinnMesh Study)

Background

Chronic pain after inguinal hernioplasty is the foremost side-effect up to 10–30% of patients. Mesh fixation may influence on the incidence of chronic pain after open anterior mesh repairs.

Methods

Some 625 patients who underwent open anterior mesh repairs were randomized to receive one of the three meshes and fixations: cyanoacrylate glue with low-weight polypropylene mesh (n?=?216), non-absorbable sutures with partially absorbable mesh (n?=?207) or self-gripping polyesther mesh (n?=?202). Factors related to chronic pain (visual analogue scores; VAS?≥?30, range 0–100) at 1 year postoperatively were analyzed using logistic regression method. A second analysis using telephone interview and patient records was performed 2 years after the index surgery.

Results

At index operation, all patient characteristics were similar in the three study groups. After 1 year, chronic inguinal pain was found in 52 patients and after 2 years in only 16 patients with no difference between the study groups. During 2 years’ follow-up, three (0.48%) patients with recurrences and five (0.8%) patients with chronic pain were re-operated. Multivariate regression analysis indicated that only new recurrent hernias and high pain scores at day 7 were predictive factors for longstanding groin pain (p?=?0.001). Type of mesh or fixation, gender, pre-operative VAS, age, body mass index or duration of operation did not predict chronic pain.

Conclusion

Only the presence of recurrent hernia and early severe pain after index operation seemed to predict longstanding inguinal pain.

     

ATP induces respiratory ciliostimulation in rat and guinea pig in vitro and in vivo.

Adenosine triphosphate (ATP) has been shown to revitalize the disturbed nasal mucociliary function in man. We investigated the effects of ATP on the ciliary beat frequency (CBF) in animals by immersing tracheal explants from rats in various concentrations of ATP, and by infusing ATP intravenously to guinea pigs. CBF was measured with a photodetector technique from the surface of the explants or from the incised trachea. ATP (from 0.01 to 1 mg/ml) in vitro increased CBF in rat tracheal explants up to 10.5% (p less than 0.05). In vivo ATP (1 mg/kg) increased the CBF by 29% (p less than 0.01) in the guinea pig trachea. As the CBF was increased by ATP, both in vitro and in vivo, it can be suggested that the improvement in mucociliary transport by exogenous ATP as shown in previous studies is caused by the ciliostimulatory effect of ATP.     

Equivalent lung deposition of budesonide in vivo: a comparison of dry powder inhalers using a pharmacokinetic method

AIMS: The aim of this study was to compare lung deposition of budesonide administered from two dry powder inhalers, Giona Easyhaler 200 microg/dose and Pulmicort Turbuhaler 200 microg/dose by utilizing a pharmacokinetic method. METHODS: This was an open, randomized, crossover study in 33 healthy subjects. The study consisted of four treatment periods separated by at least 4 wash-out days. Equivalence in lung deposition was assessed after a single inhaled 1000 microg (5 x 200 microg) dose of budesonide from Giona Easyhaler and from Pulmicort Turbuhaler. Concomitant oral charcoal administration (40 g) was used to prevent gastrointestinal (GI) absorption of budesonide. The efficacy of the charcoal was studied after oral administration of a budesonide 2 mg capsule. The subjects were trained to inhale the study drugs with controlled flow rates, which resulted in an equal pressure drop (4 kPa) across both inhalers. Venous blood samples for the determination of budesonide concentrations in plasma were drawn before and at predetermined time points up to 8 h after drug administration. Budesonide concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Several pharmacokinetic parameters were estimated, the area under the budesonide concentration in plasma vs time curve from dosing to infinity (AUC(0, infinity)) being the primary response variable. Equivalence in lung deposition was concluded if the 90% confidence interval (CI) for the Easyhaler : Turbuhaler ratio of AUC(0, infinity) fell within the limits of 0.8-1.25. RESULTS: The mean AUC(0,infinity) value after Easyhaler treatment was 3.48 (standard deviation (SD) 0.93) ng ml(-1) h and after Turbuhaler treatment 3.46 (1.13) ng ml(-1) h. The Easyhaler : Turbuhaler AUC(0, infinity) ratio was 1.02 and the 90% CI was from 0.96 to 1.09. The mean C(max) values (SD) for budesonide in plasma after Easyhaler and Turbuhaler treatments were 1.22 (0.41) ng ml(-1) and 1.29 (0.44) ng ml(-1), respectively. There was no statistically significant difference (P = 0.39) between the median t(max) for Easyhaler (30 min) and Turbuhaler treatment (23 min). Charcoal impaired the GI absorption of budesonide by 96%. The occurrence of adverse events was similar during both treatments. CONCLUSIONS: The results show that the lung deposition of budesonide from Giona Easyhaler 200 microg/dose and Pulmicort Turbuhaler 200 microg/dose dry powder inhalers is equivalent. The charcoal block used to prevent GI absorption of swallowed budesonide was found to be effective.     

Balanced physiological saline in the treatment of chronic rhinitis

The effects of a special balanced physiological saline on nasal symptoms of 93 patients with chronic rhinitis were studied. The main diagnoses of the patients were allergic rhinitis, atrophic rhinitis and ozaena, rhinitis sicca, chronic sinusitis, nasal polyposis and postoperative condition after nasal surgery. The tested solution was administered by a simple metered dose pump. 85 (91%) of the patients reported beneficial effects of the tested solution on nasal symptoms. In addition, 22 (71%) of those patients who used continuous anti-allergic medication, mainly intranasal steroids, reported that the tested solution improved the efficacy of their ordinary drug. So the tested solution proved to be beneficial in humidifying atrophic or otherwise dry mucosa, douching crusty nose and as adjuvant therapy in the treatment of allergic rhinitis.     

Once-daily theophylline in the treatment of nocturnal asthma

The efficacy and side-effects of individually adjusted doses of controlled-release theophylline given once daily in the evening (average dose 650 mg) were compared with those of standard treatment with controlled-release terbutaline 7.5 mg b.d. Thirty-six asthmatics with regular morning obstruction ("morning dipping") were studied over two treatment periods each of two weeks, according to a crossover, randomized, double blind design. Morning peak expiratory flow (PEF) was slightly but significantly higher with theophylline (363 l.min-1) than terbutaline (342 l.min-1). Feelings of dyspnoea on waking in the morning were also less pronounced with theophylline. There were no other differences between the treatment periods during the day or night, with respect to dyspnoea or any the other symptoms. Side-effects were mild and were reported with similar frequencies during both treatments. It is concluded than an individually adjusted dose of once-daily theophylline administered in the evening is at least as effective as conventional therapy with controlled-release terbutaline in preventing nocturnal and early morning asthma, when both drugs are added to regular medication with inhaled sympathomimetics and steroids.