Gatifloxacin 400 mg as a single shot or 200 mg once daily for 3 days is as effective as ciprofloxacin 250 mg twice daily for the treatment of patients with uncomplicated urinary tract infections.

The efficacy and safety of two oral dosing regimens of gatifloxacin compared with ciprofloxacin for the treatment of acute uncomplicated lower urinary tract infection was investigated in a double-blind, randomised study, in adult female patients who received either gatifloxacin (400 mg as a single shot or 3 days of 200 mg once daily) or ciprofloxacin (250 mg given twice daily for 3 days). Bacteriological and clinical responses were assessed 7-9 days after the end of treatment (EOT), and 4-6 weeks post-treatment (end of study, EOS). One thousand one hundred and two women were treated, 741 (248 in the gatifloxacin 400 mg group, 252 in the gatifloxacin 200 mg group, and 241 in the ciprofloxacin group) presented with bacteriological proof of infection and entered the efficacy analysis. The bacteriological response per patient at EOT in the three groups were 80% (177/220) [95% CI to ciprofloxacin -8.4%; 6.4%], 83% (184/222) [95% CI to ciprofloxacin -5.9%; 8.7%] and 81% (176/216), respectively. At the follow-up assessment they were slightly lower, 75% (167/224), 79% (169/213) and 79% (171/217), respectively. The clinical responses at EOT were 81% (197/243) [95% CI to ciprofloxacin -10.2%; 3.4%], 85% (213/250) [95% CI to ciprofloxacin -5.7%; 7.2%] and 85% (201/238), respectively. At EOS they were 82% (195/239), 88% (212/241) and 86% (200/233), respectively. The eradication rates for all initial pathogens at the EOT were 90.3% in the gatifloxacin 400 mg S.D. group, 90.6% in the gatifloxacin 200 mg group, and 88.3% in the ciprofloxacin group. All treatment groups showed a similar safety profile. The incidence of treatment-related adverse events was comparable, the majority of adverse events were of mild or moderate intensity and the medications were well tolerated. Both the administration of gatifloxacin 200 mg once daily for 3 days, and gatifloxacin 400 mg as a single shot were shown to be equivalent to ciprofloxacin 250 mg twice daily for 3 days for the treatment of acute uncomplicated lower urinary tract infections.

Comparison of the efficacy and tolerability of topically administered azelastine, sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis.

OBJECTIVE AND SETTING: Azelastine (AZE) in a novel, eye drop, formulation, was compared with topically applied sodium cromoglycate (SCG) and placebo (PLA) in the treatment of seasonal allergic conjunctivitis or rhino-conjunctivitis in a multicentre, parallel group study. RESEARCH DESIGN: 144 subjects ranging in age from 16 to 65 years participated. All had at least a 2-year history of seasonal allergic conjunctivitis and were symptomatic at the time of inclusion. Medications were administered topically either twice daily (AZE/PLA) or four times daily (SCG) over a 2-week treatment period. Method and outcome measures: Azelastine and placebo were compared double-blind; the comparison versus SCG was carried out in an open manner. Itching, redness, flow of tears, eyelid swelling, foreign-body sensation, photophobia, soreness and discharge were scored on a 4-point severity scale. RESULTS: Results for the decrease of main conjunctivitis symptoms (itching, tearing and conjunctival redness) showed a marked effect for both active treatments on day 3 with a sustained improvement on days 7 and 14. A clear response to treatment (an improvement of sum scores for day 3 of >/=3 points compared to baseline) occurred in 85.4% of azelastine-treated patients, 83.0% of sodium cromoglycate patients and 56.3% of placebo patients. Response rates for both active treatments were statistically superior to those for placebo (azelastine p = 0.005; sodium cromoglycate p = 0.007). Global assessment of efficacy was at least 'satisfactory' for 90.0% of azelastine patients, 81.3% of sodium cromoglycate patients and 66.3% of placebo-treated patients. The most frequent adverse effects were transient application site reactions which tended to disappear with increasing duration of treatment, and, less frequently, taste perversion. CONCLUSION: The results of this study indicate that the therapeutic use of azelastine eye drops in patients with seasonal allergic conjunctivitis or rhino-conjunctivitis can be recommended.

Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma.

BACKGROUND: Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma. METHODS: After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 microg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 microg/day (n=448) or budesonide 1600 microg/day (n=441) for 12 weeks. RESULTS: Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1-3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to "as needed" beta agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated. CONCLUSION: The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone.

A randomised, double-blind, double-dummy comparison of the efficacy and tolerability of lercanidipine tablets and losartan tablets in patients with mild to moderate essential hypertension.

A double-blind, double-dummy, randomised, multicentre study to compare the efficacy and tolerability of lercanidipine with losartan. Patients with mild to moderate hypertension (supine diastolic blood pressure (DBP) 95-115 mm Hg) were enrolled and underwent a placebo run-in period of 14-30 days before random allocation to lercanidipine tablets 10 mg once-daily (n = 234) or losartan tablets 50 mg once-daily (n = 231) during the assessment period (approximately 16 weeks). Titration to lercanidipine 20 mg once-daily (two 10 mg tablets) or losartan 100 mg once-daily (two 50 mg tablets) was allowed after 8 weeks, if necessary. At the end of the study, 71% of patients who received lercanidipine tablets had achieved normalised DBP (ie, < or =90 mm Hg) and 81% had responded to treatment (ie, DBP < or =90 mm Hg or a decrease in DBP > or =10 mm Hg). The corresponding numbers in the losartan tablets group were 65% and 78%, respectively. In those patients who required dose titration, there was evidence of a greater response with lercanidipine tablets than with losartan tablets. Both treatments were well tolerated with a low incidence of adverse drug reactions and a low withdrawal rate. In conclusion, the antihypertensive effects of lercanidipine tablets were comparable with those of losartan tablets; both treatments gave a high response rate for an antihypertensive monotherapy and were very well tolerated.

Short-duration therapy with terbinafine 1% cream in dermatophyte skin infections.

In a multicentre, double-blind, parallel-group study, the efficacy and safety of a single application of terbinafine 1% cream was compared with 3, 5 and 7 days' once-daily therapy in the treatment of tinea pedis and tinea corporis/cruris. Seventy-eight patients with tinea pedis (58 male, 20 female; mean age 36, range 19-80) and 21 patients with tinea corporis or tinea cruris (16 male, 5 female; mean age 37, range 22-72), presenting in general practice, were entered into the study. Of these, 65 patients with tinea pedis and 14 with tinea corporis or cruris completed the study and were evaluable. Twenty-eight days after commencing therapy 78, 83, 82 and 83% of patients with tinea pedis in the 1-, 3-, 5-, and 7-day treatment groups, respectively, were mycologically cured, and 61, 78, 71 and 67%, respectively, were 'effectively treated'. There was no statistically significant difference between treatment groups. Similarly high cure rates were seen in patients with tinea corporis and tinea cruris. Three months after commencing therapy there was little evidence of relapse. The study shows that there is a significant potential for short-duration therapy with terbinafine 1% cream in tinea infections of the skin, emphasized here by the high cure rates obtained following a single application.

Does naftifine have anti-inflammatory properties? A double-blind comparative study with 1% clotrimazole/1% hydrocortisone in clinically diagnosed fungal infection of the skin.

In a multicentre, double-blind, randomized, parallel group study in general practice, 269 patients with clinically diagnosed fungal infection of the skin were treated with either naftifine (Exoderil) or 1% clotrimazole plus 1% hydrocortisone (CHC; Canesten HC) applied twice daily for 4 weeks. Only 115 patients were shown subsequently to have a fungal infection by laboratory tests; the others had inflammatory disease of unknown aetiology. In those with fungal disease, both treatments were equally effective in terms of mycological cure (negative microscopy and culture). Clinical results for all 265 patients showed no clinically identifiable difference between the two preparations in terms of resolution of the disease, indicating that naftifine does have anti-inflammatory activity at least equal to CHC. This study suggests that there is no clinical advantage in treating patients with clinically diagnosed fungal infection of the skin with an antimycotic/corticosteroid combination as opposed to naftifine alone.

Early side-effects of antihypertensive therapy: comparison of amlodipine and nifedipine retard.

In a multicentre crossover study of 97 patients with mild hypertension, the incidence and severity of adverse effects were observed during the first 14 days of treatment with amlodipine, nifedipine retard or placebo. Amlodipine (5 mg) once daily was equipotent to nifedipine retard (20 mg) twice daily. At these doses, the incidence of adverse effects was significantly greater during treatment with nifedipine retard (41%) than with amlodipine (27%, P < 0.05) or placebo (16%, P < 0.01). In particular, headache and flushing occurred significantly less frequently during the first 14 days of treatment with amlodipine than with nifedipine retard. The lower incidence and reduced severity of vasodilatory side-effects associated with amlodipine resulted in fewer withdrawals during initiation of therapy (2 on amlodipine compared with 7 on nifedipine retard).

Comparison of early side effects with amlodipine and nifedipine retard in hypertension.

The frequency and severity of adverse effects during the first 14 days of treatment with amlodipine (5 mg once daily), nifedipine retard (20 mg twice daily) or placebo were compared in a multicentre, three-way, cross-over study involving 97 patients with mild-to-moderate hypertension. All three groups of patients were well matched for age, sex and baseline blood pressure. Amlodipine and nifedipine retard produced highly significant and comparable reductions in blood pressure, indicating that the doses were therapeutically equivalent. The incidence of adverse effects considered to be definitely or probably related to nifedipine retard treatment (41%) was significantly higher than for placebo (16%, p less than 0.01) or amlodipine (27%, p less than 0.05). There were no significant differences in the incidence of vasodilator-related adverse effects between amlodipine and placebo. In contrast, headache, flushing and dizziness were reported more frequently by patients while on nifedipine retard than on placebo or amlodipine. The convenience of once-daily dosing, together with a lower incidence of adverse effects, with consequently fewer withdrawals from therapy, suggests that amlodipine has clinical advantages over nifedipine retard in the treatment of hypertension.

The efficacy and tolerability of controlled-release dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hips.

A double-blind, parallel group study was undertaken in general practice to compare the efficacy of and tolerability to controlled-release (CR) dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hip(s). Eighty-six patients were randomly allocated to receive either CR dihydrocodeine (60 mg) tablets (1 tablet twice daily to 2 tablets daily) or combination dextropropoxyphene (32.5 mg)/paracetamol (325 mg) tablets (2 tablets 3-times daily to 2 tablets 4-times daily) for a period of 2 weeks. Patients recorded in a diary card 4 times a day the severity of their pain and each morning whether or not they woke during the night due to pain in their hip(s). On entry to the study, after the first week's treatment and at the final visit another week later, the investigator assessed the patient's severity of pain on passive movement of the hip and also noted the severity of any volunteered symptoms or side-effects. After 2-weeks' treatment, pain on passive movement of the hip joint was statistically significantly less severe on CR dihydrocodeine than on dextropropoxyphene/paracetamol (p = 0.02). Nausea and vomiting were more pronounced in the dihydrocodeine than in the dextropropoxyphene/paracetamol group after the first week's treatment but by the end of the study there was no significant treatment difference in any of the volunteered side-effects. Patients on CR dihydrocodeine developed some constipation as expected and the dextropropoxyphene/paracetamol patients suffered from impaired concentration. More patients withdrew on CR dihydrocodeine than on dextropropoxyphene/paracetamol but these withdrawals tended to occur early in the trial just after initiating therapy. Tolerance in terms of withdrawals or side-effect profile did not appear to the dosage of each preparation administered. It is concluded that after 2-weeks' treatment CR dihydrocodeine provided superior analgesia to dextropropoxyphene/paracetamol with no difference in side-effects. Furthermore, CR dihydrocodeine has the advantage of twice rather than 3 or 4-times daily dosing.

Controlled-release indomethacin and sustained-release diclofenac sodium in the treatment of osteoarthritis: a comparative controlled clinical trial in general practice.

A double-blind, crossover study was undertaken in general practice to compare the efficacy and tolerability of a new controlled-release indomethacin with sustained-release diclofenac sodium in patients with osteoarthritis. Eighty-four patients were randomly allocated to receive controlled-release indomethacin tablets (75 mg) or sustained-release diclofenac sodium tablets (100 mg) at night for a period of 4 weeks before being crossed-over to receive the alternative treatment for a further 4 weeks. Pain scores for day and night, duration of morning stiffness, requirement for escape analgesia, and treatment preference were similar for both treatments. There was no significant difference between treatments for incidence and severity of side-effects. It was concluded that controlled-release indomethacin tablets (75 mg) given as a single night-time dose were as efficacious and well tolerated as sustained-release diclofenac sodium (100 mg).

Comparison of the induction characteristics of thiopentone and propofol in children.

The induction characteristics of propofol 2.0-2.5 mg kg-1 were compared with those of thiopentone 4-5 mg kg-1 in 60 fit children aged between 3 and 16 yr. All patients received i.m. premedication with papaveretum 0.4 mg kg-1 (maximum dose 15 mg) and hyoscine 0.008 mg kg-1 (maximum dose 0.3 mg). Seven children (24%) complained of pain after injection with propofol, compared with three (10%) after thiopentone. No child in either group complained of severe pain. Excitatory effects were observed in 10 children (33%) receiving propofol as opposed to five children (16%) after thiopentone, but these were transient and minor and all occurred after completion of injection. Apnoea lasting longer than 30 s occurred in only four children (13%) in each group despite the use of opioid premedication. The mean duration of apnoea was similar in both groups. Propofol caused greater decreases in arterial pressures (systolic, diastolic, mean) than thiopentone, but only the difference in systolic arterial pressure achieved significance. There was a significant difference in heart rate, which did not change after propofol, but increased with thiopentone. The overall quality of induction was assessed as being good in all children receiving thiopentone compared with 20 (66%) of those receiving propofol.