Efficacy of disintegrating aspirin in two different models for acute mild-to-moderate pain: sore throat pain and dental pain.

A recently developed fast-release aspirin tablet formulation has been evaluated in two different pain models. The dental impaction pain model and the sore throat pain model are widely used for assessing analgesia, including acute mild-to-moderate pain. Both studies were double-blind, randomized, parallel group and compared a single dose of 1000 mg aspirin with 1000 mg paracetamol and with placebo and investigated the onset and overall time course of pain relief. Speed of onset was measured by the double-stopwatch method for time to meaningful pain relief and time to first perceptible pain relief. Pain intensity and pain relief were rated subjectively over a 6-h (dental pain) and 2-h (sore throat pain) time period. In both models fast-release aspirin and commercial paracetamol were statistically significantly different from placebo for onset of action, summed pain intensity differences and total pain relief. Meaningful pain relief was achieved within a median of 42.3 and 42.9 min for aspirin and paracetamol, respectively, in the dental pain model. The corresponding numbers in sore throat pain were 48.0 and 40.4 min. All treatments in both studies were safe and well tolerated. No serious adverse events were reported and no subject was discontinued due to an adverse event. Overall the two studies clearly demonstrated efficacy over placebo in the two pain models and a comparable efficacy and safety profile between aspirin and an equivalent dose of paracetamol under the conditions of acute dental pain and acute sore throat pain. Trial registration These trials were registered with ClinicalTrials.gov, registration number: NCT01420094, registration date: July 27, 2011 and registration number: NCT01453400, registration date: October 13, 2011.

Randomised, double-blind, placebo-controlled studies on flurbiprofen 8.75 mg lozenges in patients with/without group A or C streptococcal throat infection, with an assessment of clinicians' prediction of 'strep throat'.

BACKGROUND: Diagnosing group A streptococcus (Strep A) throat infection by clinical examination is difficult, and misdiagnosis may lead to inappropriate antibiotic use. Most patients with sore throat seek symptom relief rather than antibiotics, therefore, therapies that relieve symptoms should be recommended to patients. We report two clinical trials on the efficacy and safety of flurbiprofen 8.75 mg lozenge in patients with and without streptococcal sore throat. METHODS: The studies enrolled adults with moderate-to-severe throat symptoms (sore throat pain, difficulty swallowing and swollen throat) and a diagnosis of pharyngitis. The practitioner assessed the likelihood of Strep A infection based on historical and clinical findings. Patients were randomised to flurbiprofen 8.75 mg or placebo lozenges under double-blind conditions and reported the three throat symptoms at baseline and at regular intervals over 24 h. RESULTS: A total of 402 patients received study medication (n = 203 flurbiprofen, n = 199 placebo). Throat culture identified Strep A in 10.0% of patients and group C streptococcus (Strep C) in a further 14.0%. The practitioners' assessments correctly diagnosed Strep A in 11/40 cases (sensitivity 27.5%, and specificity 79.7%). A single flurbiprofen lozenge provided significantly greater relief than placebo for all three throat symptoms, lasting 3-4 h for patients with and without Strep A/C. Multiple doses of flurbiprofen lozenges over 24 h also led to symptom relief, although not statistically significant in the Strep A/C group. There were no serious adverse events. CONCLUSIONS: The results highlight the challenge of identifying Strep A based on clinical features. With the growing problem of antibiotic resistance, non-antibiotic treatments should be considered. As demonstrated here, flurbiprofen 8.75 mg lozenges are an effective therapeutic option, providing immediate and long-lasting symptom relief in patients with and without Strep A/C infection.

Nonprescription ibuprofen and acetaminophen in the treatment of tension-type headache.

A single-dose, double-blind, randomized clinical trial was conducted to examine the relative analgesic effectiveness of 400 mg of ibuprofen (n = 153), 1,000 mg of acetaminophen (n = 151), and placebo (n = 151) in volunteers with muscle contraction headache. At regular intervals during a 4-hour period, participants evaluated headache pain intensity on a 100-mm visual analog scale and headache pain relief on a six-category scale. Both active agents were significantly different from placebo at all time points and in reducing pain intensity and providing relief of headache overall. Similarly, ibuprofen at 400 mg differed significantly from acetaminophen at 1,000 mg on both rating scales. Participants receiving ibuprofen at 400 mg achieved complete relief of headache faster than those receiving acetaminophen at 1,000 mg or placebo, and more participants taking ibuprofen experienced complete relief of headache than those taking placebo or acetaminophen. Both ibuprofen at 400 mg and acetaminophen at 1,000 mg are efficacious analgesic agents for muscle contraction headache, and ibuprofen at 400 mg is significantly more effective than acetaminophen at 1,000 mg for treating this condition.

A placebo-controlled model to assay the onset of action of nonprescription-strength analgesic drugs.

The definition and detection of the onset of analgesic drug activity represent two of the more complicated methodologic challenges in clinical pharmacology. We addressed these issues by designing an analgesic assay with frequent posttreatment assessments to identify the first time when a subject experienced relief and when a nonprescription-strength analgesic could be distinguished from placebo. To test the feasibility of conducting this assay, 29 subjects with acute sore throat were randomized to receive 200 mg ibuprofen, 400 mg ibuprofen, or placebo under double-blind conditions. To identify the onset of analgesia, subjects used three rating scales at 5-minute intervals over the first hour. Subjects completed each series of assessments efficiently, most within 5 seconds. Each active agent was differentiated from placebo early after treatment (p < or = 0.05), and there was dose-separation. We conclude that the sore throat pain model can be used to evaluate the onset of action of nonprescription-strength analgesic agents.

A placebo-controlled model for assaying systemic analgesics in children.

To assess the sore throat pain model in children as an assay for systemic analgesic agents in children under double-blind, placebo-controlled conditions, we conducted a single-dose parallel study that compared 10 mg/kg ibuprofen (n = 39), a new analgesic agent for children, and 15 mg/kg acetaminophen (n = 38), an approved analgesic for children, to placebo (n = 39) in children from 2 to 12 years of age with acute sore throat. At 1/2, 1, 2, 3, 4, 5, and 6 hours (2 hours in the pediatrician's office followed by 4 hours at home), children assessed pain intensity with a pain thermometer and pain relief with a smiley-face scale. The parent and pediatrician assessed pain intensity and change in pain; the parent also provided an overall evaluation at 6 hours. The children rated ibuprofen and acetaminophen as significantly effective compared with placebo (p < 0.05) on both scales at most posttreatment time points and overall. The parent and pediatrician also rated both active medications as significantly different from placebo on both of their scales (p < 0.05) at several time points and overall. On the parent's overall evaluation, ibuprofen was rated as effective compared with placebo (p < 0.05). Both active agents significantly (p < 0.05) reduced oral temperature in children with baseline temperatures > 99 degrees F. No treatment-related adverse effects were observed. We conclude that the sore throat pain model is a sensitive assay for identification of the activity of oral analgesic drugs in children and that ibuprofen is an effective analgesic in children.

Headache pain model for assessing and comparing the efficacy of over-the-counter analgesic agents.

To refine the assessment of over-the-counter analgesic agents in the treatment of muscle-contraction headache, we designed a single-dose model with attention to specific methodologic features and two relevant assessments--the percentage of subjects who achieve complete relief and the time until pain is no longer experienced. Subjects were randomly assigned to receive a single dose of 1000 mg acetaminophen, 1000 mg aspirin with 64 mg caffeine, or placebo. Under double-blind conditions, subjects rated headache pain intensity and relief over 4 hours and provided a Comparative Evaluation at the end of the trial. Both active agents were significantly distinguished from placebo on the time-point analyses (p less than 0.05) and summary end point measurements (sum of pain intensity difference [SPID], total of pain relief, percentage of patients with complete relief, percentage of treatment failures, and the Comparative Evaluation), as well as causing a faster elimination of headache (p less than 0.05). The aspirin-caffeine combination was rated higher than acetaminophen on all summary measurements, particularly SPID (p less than 0.05), with significantly more patients obtaining complete relief with aspirin-caffeine (p less than 0.01) than with acetaminophen. We conclude that this headache pain model can be used to demonstrate the efficacy of over-the-counter analgesic agents and to assess their relative efficacy.

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.

Inhaled epinephrine and oral theophylline-ephedrine in the treatment of asthma.

Inhaled and oral over-the-counter bronchodilators are used for self-therapy by asthmatic patients. To evaluate their safety and efficacy, we compared epinephrine and theophylline combined with ephedrine with inhaled metaproterenol and the placebo. Twelve asthmatic patients were studied in a randomized, double-blind, placebo-controlled, crossover trial comparing forced expiratory volume in 1 second (FEV1) after two inhalations of epinephrine (0.2 mg/inh), 1 minute apart, followed in 15 minutes by theophylline (130 mg) with ephedrine (24 mg) versus two inhalations of metaproterenol (0.65 mg/inh), 1 minute apart, versus placebo inhaler and tablets. Onset of FEV1 greater than 15% above baseline values occurred within 15 seconds after inhalations for 100% of epinephrine-treated patients, 92% of metaproterenol-treated patients, and 33% of placebo-treated patients. FEV1 responses were significantly greater (P less than .05) for epinephrine at 0.66 to 1.66 minutes compared with the responses of metaproterenol, and epinephrine and theophylline that was combined with ephedrine compared with metaproterenol beginning at 2 hours. Mean duration of activity was 5.7 hours for the epinephrine- and theophylline with ephedrine-treated patients, 4.9 hours for metaproterenol-treated patients, and 2 hours for the placebo group. There were statistically significant differences for patients receiving epinephrine and theophylline with ephedrine versus the placebo group (P less than .001), metaproterenol patients versus the placebo group (P = .02), and patients receiving epinephrine and theophylline with ephedrine versus metaproterenol-treated patients (P less than .05). Compared with inhaled metaproterenol, inhaled epinephrine followed in 15 minutes by a theophylline-ephedrine tablet had a significantly earlier onset, longer duration of action, numerically greater peak effect, and patient preference.(ABSTRACT TRUNCATED AT 250 WORDS)

Ibuprofen and acetaminophen in the relief of acute pain: a randomized, double-blind, placebo-controlled study.

To determine the relative analgesic efficacy of ibuprofen 400 mg and acetaminophen 1000 mg, we conducted a single-dose, double-blind, placebo-controlled, randomized clinical trial using a standard assay for analgesic agents, the dental pain model. At regular intervals over 6 hours, 184 patients who had undergone dental impaction surgery rated pain intensity and relief on categorical scales and pain half-gone on a dichotomous nominal scale; a categorical overall evaluation was completed at the end of 6 hours. Both active agents were effective compared to placebo. Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for Sum Pain Intensity Difference (SPID), Total Pain Relief (TOTPAR), sum pain half-gone, and overall evaluation (P less than .05 to P less than .001). The time-effect curves demonstrated a greater peak effect and longer duration of action for ibuprofen 400 mg compared to acetaminophen 1000 mg. Side effects were reported in five ibuprofen patients, 11 acetaminophen-treated patients, and seven placebo patients. Based on the results of this clinical study, we conclude that ibuprofen 400 mg is a safe and more effective analgesic than acetaminophen 1000 mg for patients with acute pain.

Ibuprofen and acetaminophen in the relief of postpartum episiotomy pain.

A single-dose, double-blind, randomized clinical trial was conducted to examine the relative analgesic efficacy of ibuprofen 400 mg (n = 36), acetaminophen 1000 mg (n = 37), and placebo (n = 38) in postpartum patients who had moderate to severe pain after episiotomy. At regular intervals over 4 hours, patients evaluated pain severity and relief on categorical scales and completed a categorical overall evaluation at the end of the trial. Both active agents were effective compared with placebo (P less than .05). Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for the sum of pain intensity difference, total pain relief, and reduction of pain by more than 50% (P less than .05), suggesting a more rapid onset of action and a more prolonged effect by ibuprofen 400 mg. No adverse effects were reported. Based on the results of this conventional postpartum episiotomy pain model, both agents are considered efficacious and ibuprofen 400 mg is a more effective analgesic for the relief of acute pain than acetaminophen 1000 mg.

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.

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.

The pediatric nurse practitioner: origins and challenges.

During the past decade, a new health professional has evolved--the pediatric nurse practitioner (PNP). Responding to warnings of a shortage of primary care physicians, the American Academy of Pediatrics helped encourage programs to train PNPs who would provide well-child care, working under a physician's supervision. Simultaneously, in response to changing attitudes by and toward nurses, the American Nurses' Association expressed support for the expanded role of nurses in direct patient care functions--an expansion that would supplement other new academic programs in advancing the status of nursing as an interdependent, rather than subsidiary, health profession. Although mutually aiming at improvements in health care, both professions thus acted with different motivations and goals that have produced ongoing conflicts. These conflicts have been intensified by the absence of long-range planning in federal programs that have supported training for nurse practitioners. This paper summarizes the history of the PNP movement and the unresolved problems created by this new health professional.