Caffeine as an analgesic adjuvant. A double-blind study comparing aspirin with caffeine to aspirin and placebo in patients with sore throat.

Despite its frequent clinical use in analgesic agents, caffeine has not been accepted unequivocally as an analgesic adjuvant. To evaluate this activity of caffeine, we used new study methods in a randomized controlled trial on patients with acute sore throat due to tonsillopharyngitis. Patients were randomly assigned to receive a single dose of one of three treatments: 800 mg of aspirin with 64 mg of caffeine (n = 70), 800 mg of aspirin (n = 68), or placebo (n = 69). Under double-blind conditions, during a 2-hour evaluation period, patients used different rating scales to assess pain intensity, change in pain, relief, and two qualities of throat pain, how swollen the throat felt, and difficulty swallowing. Aspirin with caffeine and aspirin alone were significantly more effective than placebo for all efficacy measurements from 30 minutes through 2 hours and overall. The aspirin-caffeine combination also showed evidence of activity at 15 minutes on the relief scale. Aspirin with caffeine was more effective than aspirin alone after 30 minutes and over the entire study period. For patients with fever, both active treatments were equally effective antipyretic agents. We conclude, therefore, that 800 mg of aspirin, given alone or with 64 mg of caffeine, is an effective analgesic and antipyretic agent. Because the aspirin-caffeine combination is significantly more effective than aspirin alone as an analgesic, we also conclude that 64 mg of caffeine is an analgesic adjuvant.

Subjective and objective features of sore throat.

This study examines the relationship between the symptom of sore throat and the signs of pharyngitis. Patients seeking medical attention for sore throat were examined by their physician, who documented findings on a Tonsillopharyngitis Score (TPS) and obtained a throat culture. Each patient was then instructed by the physician's assistant to characterize the severity of throat pain on a Sore Throat Pain Intensity Scale (STPIS) and Sore Throat Questionnaire. A high positive correlation was found for the STPIS and TPS but not for these findings and the cause of pharyngitis. A similar association was found between the relative severity of throat pain and the words patients use to describe it. This new method objectively confirms the subjective rating of sore throat pain.

Sore throat pain in the evaluation of mild analgesics.

A double-blind, single-dose parallel study was conducted to assess refinements of a previously tested model for evaluating treatment of sore throat pain. Patients with tonsillopharyngitis randomly received either 400 mg ibuprofen (n = 39), 1000 mg acetaminophen (n = 40), or placebo (n = 41). At hourly intervals for 6 hours the patients reported pain intensity and pain relief on conventional scales and two sensory qualities of throat pain ("swollen throat" and "difficulty swallowing") on two new visual analog scales. Both active agents were significantly more effective than placebo for all efficacy measurements (p less than 0.01). Ibuprofen, 400 mg, was more effective than acetaminophen, 1000 mg, on all rating scales, conventional and new, at all time points after 2 hours and overall (p less than 0.01). There were no side effects. We conclude that sore throat is a pain model that can be used to discriminate between active medication and placebo, as well as between two effective over-the-counter analgesics.

Role of hypnotic drugs in general practice.

General practice physicians commonly deal with patients who report experiencing insomnia. Advances in our understanding of insomnia should result in much more effective diagnosis and therapeutic intervention for insomnia patients at the primary care level. This presentation highlights the new knowledge of insomnia pertinent to general practice physicians and discusses the rational use of hypnotic medications in primary care.

Guanfacine as monotherapy for systemic hypertension.

Three clinical studies examined the effects of guanfacine as monotherapy. Study 1 was a double-blind, randomized, parallel trial with a placebo control with 26 patients with mild essential hypertension treated with 1-mg guanfacine or matching placebo daily at bedtime for 8 weeks. Pretreatment and posttreatment determinations of plasma volume, plasma aldosterone and blood pressure (BP) were made in all 26 patients. There were no significant differences between guanfacine and placebo with regard to changes in plasma volume or plasma aldosterone, but a significant decrease (p = 0.001) in both diastolic and mean BPs was seen with the active drug. No side effects were reported. From this study, it was concluded that guanfacine monotherapy is an effective and well-tolerated initial treatment for mild essential hypertension with no effect on either plasma volume or plasma aldosterone. Study 2 was a double-blind, randomized, parallel clinical study with placebo control with 42 patients with mild essential hypertension treated with either guanfacine (1 mg/day) or matching placebo at bedtime for 8 weeks. Pretreatment and posttreatment evaluations of serum cholesterol, triglycerides, low density lipoproteins, very low density lipoproteins and high density lipoproteins revealed no significant differences between the treatment and the placebo groups. A statistically significant (p less than 0.0001) decrease in diastolic BP was seen in the guanfacine group compared with those patients who received placebo. Guanfacine monotherapy was again shown to be an effective initial treatment for mild essential hypertension with no adverse influence on serum lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of guanfacine versus clonidine for efficacy, safety and occurrence of withdrawal syndrome in step-2 treatment of mild to moderate essential hypertension.

Guanfacine, an alpha 2-adrenoceptor agonist, was compared with clonidine as step-2 therapy of mild to moderate essential hypertension in a 24-week, double-blind, randomized, parallel evaluation to determine efficacy, safety and occurrence of withdrawal syndrome. During a 5-week period, patients were weaned from current antihypertensives, if any, and stabilized on step-1 therapy with 25 mg of chlorthalidone once a day. Those with a diastolic blood pressure (BP) from 95 to 114 mm Hg while taking chlorthalidone were randomized to treatment. The 2 agents had equal efficacy; 149 of 270 patients treated with guanfacine (55%) and 164 of 276 treated with clonidine (59%) achieved goal diastolic BP of less than or equal to 90 mm Hg. Terminations because of adverse effects were relatively low. Dry mouth (30% of guanfacine and 37% of clonidine groups) and somnolence (21% of guanfacine and 35% of clonidine groups, p less than 0.05) were reported most frequently. Nonsyncopal dizziness was reported in 11% of guanfacine-treated and 8% of clonidine-treated patients. This difference was not statistically significant. To evaluate the occurrence of a withdrawal syndrome in 316 outpatients and 156 inpatients, vital signs were monitored at least twice a day for up to 7 days after the end of therapy. Segmented 24-hour urine studies were performed on inpatients. Abrupt withdrawal of clonidine produced a rapid increase in diastolic and, especially, systolic BP, whereas guanfacine withdrawal produced more gradual increases. The differences were significant over the first 3 withdrawal days. It is concluded that guanfacine is a safe, effective, second-generation alpha 2-adrenoceptor agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind evaluation of temazepam, flurazepam, and placebo in geriatric insomniacs.

The efficacy and safety of temazepam (30 mg) were compared with the efficacy and safety of flurazepam hydrochloride (30 mg) and placebo in a four-day, double-blind study in 75 geriatric convalescent-home patients with insomnia. The efficacy and safety profiles of the two active drugs were similar. Patients treated with temazepam, however, reported significantly less drug hangover both on awakening and during the entire day after each night of treatment than did patients receiving flurazepam or placebo. The difference between temazepam and flurazepam was probably due to the drugs' markedly different half-lives, temazepam's mean half-life being ten hours compared with 65.5 hours for the active metabolite of flurazepam. It is well recognized that the elderly may be especially sensitive to the adverse effects associated with the accumulation of the long-acting metabolite of flurazepam. Since temazepam has no active metabolites and minimal accumulation, it is a particularly appropriate hypnotic for use in geriatric patients.

A double-blind comparison of transdermal clonidine and oral captopril in essential hypertension.

In a double-blind study, patients with mild essential hypertension were randomly assigned to treatment with transdermal clonidine or oral captopril. After a two- to three-week titration period, blood pressure decreased significantly from 146.3/95.4 to 134.7/85.1 mmHg in the 33 clonidine-treated patients and from 143.0/96.1 to 134.8/87.1 mmHg in the 35 captopril-treated patients; the mean daily doses were 0.2 mg (equivalent) of clonidine and 122.9 mg of captopril. After eight weeks of treatment, blood pressures were reduced to 132.9/85.2 mmHg in the clonidine group (n = 22) and 131.2/82.5 mmHg in the captopril group (n = 16). In black patients, blood pressure reductions were greater with clonidine than with captopril. Four patients were withdrawn from treatment because of side effects in the clonidine group and one in the captopril group. No between-group differences were found in the responses to a quality-of-life questionnaire completed before and after treatment. The clonidine patches were worn during 99% of patient-weeks of treatment; captopril was taken as directed during 64% of patient-weeks of treatment. It is concluded that transdermal clonidine is safe and effective and well accepted by hypertensive patients.

Long-term treatment with transdermal clonidine in mild hypertension.

Long-term antihypertensive treatment by once-weekly application of transdermal clonidine patches, in doses equivalent to 0.1, 0.2, 0.3 mg of clonidine daily, was evaluated in an open trial of 41 patients with baseline seated diastolic blood pressures of 90 to 103 mmHg. In all the patients, seated diastolic blood pressure was reduced to less than 90 mmHg with transdermal clonidine alone at the end of a dose titration phase of two to six weeks. Thirty-two patients successfully completed at least 22 months of therapy; three patients withdrew because of lack of efficacy and six because of adverse events. In the second treatment year 14 patients required a concomitant diuretic. Mean reductions in seated diastolic blood pressure from baseline values were statistically significant (P less than 0.0001) at all study intervals. The incidence of patient withdrawals resulting from the development of contact dermatitis at the patch application site was 5%; skin irritation not requiring withdrawal occurred in 13 patients during the first year of treatment and in two during the second. The incidence of dry mouth (in 7%) and drowsiness (in 10%) was lower than has been reported during oral clonidine therapy (40% and 35%). The results suggest that transdermal clonidine may be beneficial for the maintenance therapy of many patients with mild hypertension.

Fiorinal with codeine in the treatment of tension headache--the contribution of components to the combination drug.

The contribution of the Fiorinal and codeine phosphate components to the effectiveness of the Fiorinal with Codeine combination in the treatment of tension headache symptoms was evaluated in a randomized, placebo-controlled, multicenter double-blind study. Patients admitted to the trial took two capsules of Fiorinal with Codeine, Fiorinal alone, codeine alone, or placebo during each of two tension headache attacks. Immediately before and at intervals up to four hours after drug ingestion, patients rated pain severity, pain relief, the tense and uptight feeling, and muscle stiffness. The response to treatment was evaluated in 154 patients. Despite a high placebo response, a factor known to obscure the contribution of components, Fiorinal and codeine were each found to contribute significantly to the therapeutic effect of the Fiorinal with Codeine combination. Statistical or borderline superiority of the combination drug over Fiorinal alone was seen most frequently at the early evaluations, a finding that reflected the rapid onset of action of codeine. Statistically significant differences between Fiorinal with Codeine and codeine alone seen principally at the later assessments reflected the long duration of action of the Fiorinal component. The frequency of adverse reactions did not differ significantly among the four study groups.

Body composition and blood pressure in children based on age, race, and sex.

We evaluated 675 nine- and twelve-year-old children for body composition and circulatory differences based on age, race, and sex. The specific variables measured included height, weight, triceps and subscapula skinfolds, body mass index, percentage fat, fat-free weight, and systolic, diastolic, and mean arterial blood pressures. A 2 x 2 x 2 factorial multiple analysis of variance (MANOVA) test of significance showed body composition and blood pressure differences (P < .01) for race, age, and sex. The univariate test of the specific variables within the factors showed that black children had higher fat-free weights and lower fat levels but higher blood pressure values (P < .05) than white children. Boys had lower fat levels than girls, and the older children had higher values on the body composition variables but not on blood pressure. Zero order correlations between body composition and blood pressure ranged from 0.14 to 0.55; systolic blood pressure and body weight shared the highest correlation. These data show that, although black children have less body fat than white children, they are heavier and have higher blood pressure. We hypothesize that some aspect of fat-free body weight may contribute to hypertension in black individuals.

Health fitness training responses of normotensive and elevated normotensive children.

Abstract The purpose of this study was to compare health fitness profiles of normotensive (blood pressure < 108/76) and elevated normotensive (blood pressure ≥ 108/76) children and to evaluate the health fitness training responses of children with higher and lower blood pressures to a regular program of exercise over an eight month period. The subjects were 386 fourth grade students (lower blood pressures = 305; higher blood pressures = 81). They were measured for height and weight and evaluated before and after an exercise intervention program for flexibility, muscular endurance, cardiovascular endurance, and body fat levels. The results show that children with higher blood pressures were fatter and had lower cardiovascular fitness levels before and after the intervention. They had health fitness profiles similar to hypertensive adults. Their rate of health fitness improvement, with training, was similar to children with lower blood pressures. Therefore, elevated normotensive children have an increased risk of cardiovascular disease but can change their risk profile with regular exercise.

Double-blind evaluation of the efficacy and safety of temazepam in outpatients with insomnia.

1 The efficacy and safety of temazepam 30 mg, compared with glutethimide 500 mg and placebo, were evaluated in double-blind conditions in a 4-day study in 75 outpatients with a history of insomnia. 2 Temazepam and glutethimide were rated by the patients as effective and significantly superior to placebo for general quality of sleep, time required to fall asleep, frequency of nocturnal and early morning awakenings, and duration of sleep. 3 Residual effects reported for temazepam and glutethimide immediately after awakening and during the day were similar to or less than those reported for placebo.