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.

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).

Side effects of dihydropyridine therapy: comparison of amlodipine and nifedipine retard.

The efficacy and tolerability of amlodipine (5 mg, once daily), nifedipine retard (20 mg, twice daily), and placebo were compared in a multicenter, three-way, crossover study involving 97 patients with mild-to-moderate hypertension. Each patient underwent three, 2-week treatment periods separated by 2-week washout periods without therapy. Comparable and significant (p < 0.05) blood pressure reductions were observed after amlodipine and nifedipine retard when compared with placebo, except in the case of supine systolic blood pressure with nifedipine retard. A significantly greater incidence of treatment-related side effects was observed with nifedipine retard (41%) compared with amlodipine (27%, p < 0.05) or placebo (16%, p < 0.01). Amlodipine treatment was associated with significantly fewer reports of headache and flushing than nifedipine retard (p < 0.05). The lower incidence and reduced severity of vasodilator side effects associated with amlodipine resulted in fewer withdrawals and a better overall tolerability profile.

Oilseed rape--a new allergen?

Oilseed rape (Brassica napus) is a commonly grown crop in Europe and it has been suggested that its pollen may be a potent new allergen. The prevalence of sensitization in a normal exposed population and an objective study of those patients found to be allergic to the rape pollen is described. The results show a low prevalence of allergy to oilseed rape pollen (less than 0.2%) unless the subjects were occupationally exposed. Those affected, with one exception, were already atopic and allergic to other pollens. The role of volatile materials given off by the plant remains to be elucidated.

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.

Long-term treatment of hypertension in the elderly with a combination of atenolol and nifedipine.

The efficacy and tolerability of a once-daily, fixed combination of 50 mg atenolol and 20 mg nifedipine slow release were evaluated in a 12-month open study of 27 elderly hypertensives who were either newly presenting patients or were those who were inadequately controlled on previous monotherapy or had unacceptable side-effects with their current therapy. After 1-month's therapy with the combination, the mean sitting blood pressure 1 to 4 hours post-dose decreased from 176/103 mmHg to 146/83 mmHg and was maintained at this level for the remainder of the study. Eight patients complained of side-effects on study entry. Sixteen had complaints at some time during the 12 months of fixed combination treatment and 4 were withdrawn because of side-effects. Dizziness occurred in 6 patients on the combination but, as with side-effects overall, tended to resolve with time; its occurrence did not appear to correlate with the on-treatment blood pressure. In this group of elderly hypertension patients, therefore, the combination therapy with atenolol plus nifedipine slow release appeared to exert a greater antihypertensive effect compared with previous therapy, which included atenolol alone, with no evidence of tachyphylaxis and was reasonably well-tolerated over a 12-month period.

Depression, dementia and disability in the elderly.

A structured sample of mobile elderly patients in a rural community practice was assessed on validated rating scales for depression, dementia and disability. A total of 62% of the sample was abnormal on at least one variable. The overall prevalence of depression was 13%; the overall prevalence of dementia was either 10 or 18% depending on the criterion of Mental Test Score (MTS). Depression and dementia were related, depression being more common in females. In depressed and demented patients, MTS was age-related in those over 60 years; in depression alone, MTS was not age-related. Dementia was age-related, particularly over the age of 75. Disability increased with age and was more common in females. Disability was associated with both depression and dementia.

Normal erythrocyte sedimentation rate in the elderly.

Two hundred subjects aged 60-89 were selected for a study aimed at defining a reference range for the erythrocyte sedimentation rate in the elderly. The study extended a previous survey in subjects aged 20-65. The results confirmed that the sedimentation rate increases with age and that women have higher values than men but suggested that over half of elderly patients with disease would have rates within the previously defined "normal" range. It is therefore suggested that an erythrocyte sedimentation rate exceeding 19 mm in the first hour in elderly men and 22 mm in the first hour in elderly women warrants investigation.

A naturalistic study of hypertension in a rural U.K. community. 2 Years results.

A naturalistic study was set up to screen, identify and treat hypertensive patients aged 20-60 years in a rural general practice. 3,222 patients (92%) of a stable population of 3,489 were screened by 2 nurse research assistants and of these 455 patients (14%) were found to be hypertensive or borderline hypertensive. After careful assessment, 192 of these patients were found suitable for treatment and subsequently 138 entered the study. Two well recognised treatment regimes were used and no significant difference between patient response resulted. 84 patients (60.9%) completed the 2 year duration of the study discussed here. The cost of the study is not feasible in an average general practice, but day to day running of such a project, run along clearly defined treatment regimes was managed easily by 2 research assistants: this reduced, therefore, the work load on individual general practitioners.

Longer term effects of live influenza vaccine in patients with chronic pulmonary disease.

WRL 105 strain live influenza vaccine or placebo was given to patients with chronic bronchitis in a double-blind study. The twenty-one vaccinated and twenty-three placebo-treated patients made daily self-assessments of the severity of symptoms of cough, breathlessness, tightness, wheeze, and sputum production in the following 20 weeks. Symptom scores in the first 2 weeks after vaccination or treatment with placebo were used to calculate a baseline range for each patient. Comparison of symptoms in the two groups in the baseline period showed that symptoms were more often reported by vaccinated than by placebo-treated patients but the differences were not statistically significant. One patient who responded serologically to vaccination had a moderately severe influenzal illness starting on the day after vaccination. Comparison of symptom scores during the 18-week surveillance period with baseline values showed that symptoms of breathlessness, tightness, wheeze and cough were significantly more common in vaccinated than in placebo-treated patients and that antibiotic usage was more common in the vaccinated group.

Pharmacokinetics--uses and abuses.

It is apparent from studying recent articles on pharmacokinetics that a number of misunderstandings exist, both about the design of experiments and the analysis of results. The purpose of this paper is to outline many of the common pitfalls associated with the design of experiments and also the limitations upon the analysis of results. The paper describes mathematical, laboratory and clinical aspects which must be examined in designing a protocol for pharmacokinetic experiments. Simulated data is presented to demonstrate the dangers of using standard computer programs for parameter estimation. Even when convergence is obtained the answers may be dependent on the method employed. A mathematical model is of little use unless a reasonable amount of good, accurate data is obtained.