Sports-Related Concussion in Helmeted vs. Unhelmeted Athletes: Who Fares Worse?

In the management of sports-related concussion, little is known about the effect of wearing or not wearing a helmet (i. e., helmet status) on the acute outcomes of concussed athletes. We endeavored to assess acute neurocognitive and symptom changes after SRC in helmeted vs. unhelmeted athletes. In a retrospective study, 1 025 athletes from 2 regional databases sustained a SRC. Athletes were matched by age, gender, number of prior concussions, and days to post-concussion test, yielding a final cohort of 138 athletes. For each group of 69, differences in post-concussion neurocognitive and symptom scores were compared using group mean differences as well as reliable change index (RCI) scores set at the 80% confidence interval. With gender, prior concussions, and days to post-concussion test similar in each group, using group mean change scores and RCI methodology, we found no significant differences between the helmeted and unhelmeted groups in 4 neurocognitive tests and one total symptom score. In a cohort of carefully matched athletes from 2 regional concussion centers, helmet status was unrelated to neurocognitive scores and total symptoms in athletes after suffering a SRC. These findings suggest that acute outcomes in helmeted vs. unhelmeted sports are quite similar.

Nalbuphine, acetaminophen, and their combination in postoperative pain.

In a double-blind study with the use of subjective reports of patients as indices of analgesia, we compared the analgesic effect of oral nalbuphine and acetaminophen and determined the contribution of each to the efficacy of their combination. In this parallel 2 X 2 factorial study, 129 inpatients after surgery were randomly assigned to treatment with a single oral dose of nalbuphine hydrochloride (30 mg), acetaminophen (650 mg), the combination of nalbuphine (30 mg) and acetaminophen (650 mg), or placebo. In the factorial analysis, both the nalbuphine and acetaminophen effects were significant for virtually every measure of total and peak analgesia, whereas the interaction contrast was not significant for any measure of analgesic effect. This indicates that the analgesic effect of the combination represents the additive effect of its constituents and is consistent with the results of studies of combinations of codeine and other opioids with aspirin or acetaminophen. There were few adverse effects other than sedation, which occurred twice as frequently in patients treated with nalbuphine as in those receiving acetaminophen or placebo. Our data suggest that this combination should prove at least as effective as any currently marketed narcotic-containing combination. Since nalbuphine has less dependence liability than narcotics and exhibits a ceiling on respiratory depression, its combination with acetaminophen should also be safer than comparable narcotic combinations.

Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain.

We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti-inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose-response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action.

Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain.

Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen, aspirin, or their mixture. Our objective was to determine whether similar enhancement of analgesia could be demonstrated when caffeine is combined with ibuprofen. On a double-blind basis, a single oral dose of ibuprofen (50, 100, or 200 mg), a combination of ibuprofen, 100 mg, with caffeine, 100 mg, a combination of ibuprofen, 200 mg, with caffeine, 100 mg, or placebo was randomly assigned to 298 outpatients with postoperative pain after the surgical removal of impacted third molars. With a self-rating record, subjects rated their pain and its relief hourly for 8 hours. All active treatments were significantly superior to placebo, and the caffeine effect was significant for every measure of analgesia. Relative potency estimates indicated that the combination was 2.4 to 2.8 times as potent as ibuprofen alone. The combination also had a more rapid onset and longer duration of analgesic action. The analgesic adjuvancy of caffeine clearly extends to combinations with nonsteroidal anti-inflammatory drugs other than acetaminophen or aspirin.

A double-blind evaluation of the nocturnal antisecretory effects of anisotropine methylbromide in man. Dose response and duration of action studies.

The effects of graded doses of anisotropine methylbromide on nocturanl gastric secretion were investigated in a double-blind crossover study in man. Single doses considerably higher than those usually employed for daytime use in adjunctive therapy of peptic ulcer disease significantly reduced acid secretion without significantly influencing heart rate, blood pressure, visual acuity, or visual accommodation. The duration of action of large doses was then evaluated in fasted and nonfasted subjects. A single dose reduced acid secretion for up to 8 hours, eliminating the nocturnal elevation of acid secretion characteristic of the normal circadian pattern. Near visual acuity and accommodation decreased, an effect more pronounced in fasted subjects, but the magnitude of visual impairment was small. These findings provide the basis for a controlled trial of high-dose nighttime therapy in peptic ulcer disease.

Effect of nighttime anisotropine methyl bromide of duodenal ulcer healing and pain: a double-blind controlled trial.

Anisotropine methyl bromide, an anticholinergic, 80 mg given orally at 8 P.M., suppresses gastric acid secretion through the night without significant side effects. Thirty patients with endoscopy-proved symptomatic duodenal ulcer disease completed a randomized, double-blind, placebo-controlled trial of nighttime anisotropine methyl bromide therapy. Eleven (69 per cent) of 16 anisotropine methyl bromide-treated and six (43 per cent) of 14 placebo-treated subjects healed their ulcers within two weeks of starting treatment. The anisotropine methyl bromide-treated subjects averaged 0.63 +/- 0.27 (mean +/- S.E.) episodes of nocturnal pain during the treatment period versus 2.71 +/- 1.08 episodes in the placebo group (P = 0.06). This is the first reported study of this type designed to evaluate the efficacy of an anticholinergic agent in the healing of duodenal ulcers. Although not conclusive, the results suggest nighttime anisotropine methyl bromide therapy may be useful in the treatment of duodenal ulcer disease. Further studies seem warranted.

An evaluation of the analgesic efficacy of proquazone and aspirin in postoperative dental pain.

The analgesic efficacy of 75, 150, and 300 mg proquazone, a new nonsteroidal antiinflammatory agents, was compared to that of 650 mg aspirin and a placebo in outpatients who had moderate or severe pain following the surgical removal of impacted third molars. Estimates of the relative potency of proquazone to aspirin ranged from 4.9 to 6.2 for total analgesic effect and from 7.7 to 8.4 for peak analgesic effect. Each dosage level of proquazone and aspirin provided significant analgesia compared to placebo and was well tolerated. Adverse effects were transitory and did not appear to be dose related for proquazone.

A 12-hour evaluation of the analgesic efficacy of diflunisal, aspirin, and placebo in postoperative dental pain.

Two-hundred and one outpatients with postoperative pain following oral surgery were randomly assigned, on a double-blind basis, a single oral dose of diflunisal (250, 500, or 1000 mg), aspirin (650 mg), or placebo. Using a self-rating record, the subjects rated their pain and its relief hourly for 12 hours after medication. Measures of peak and total analgesia were derived from the patients' subjective reports. Diflunisal 250 and 1000 mg were significantly superior to aspirin for every measure of total and peak analgesia; the 500-mg diflunisal dose was significantly superior to aspirin for measures of total analgesia only. All doses of diflunisal were significantly superior to aspirin and placebo at each hour from hour 3 through hour 12. Approximately 60 per cent of the patients treated with diflunisal completed the 12-hour observation period without the need for additional analgesic therapy. Adverse effects were mild and transitory and occurred in less than 10 per cent of the patients.

The effect of food on bromfenac, naproxen sodium, and acetaminophen in postoperative pain after orthopedic surgery.

STUDY OBJECTIVES: To evaluate the effect of a standard meal on bioavailability of bromfenac, and on the relative analgesic efficacy and adverse effect liability of bromfenac 25 mg, naproxen sodium 550 mg, and acetaminophen 325 mg in the treatment of pain after orthopedic surgery. DESIGN: Randomized, double-blind, single-dose, parallel-group. SETTING: Two wards of the orthopedic surgery department at the Central Hospital, Karlstad, Sweden. PATIENTS: Three hundred ten patients with steady, moderate, or severe pain within 72 hours after orthopedic surgery. INTERVENTIONS: Patients were randomly assigned both to receive a standard meal or remain in a fasted state, and to treatment with a single oral dose of bromfenac 25 mg, naproxen sodium 550 mg, or acetaminophen 325 mg, when they experienced steady, moderate, or severe pain that required an analgesic. Using a self-rating record, subjects rated their pain and its relief for up to 8 hours after medicating. Blood samples were obtained from all patients using one of two schedules. MEASUREMENTS AND MAIN RESULTS: The peak plasma bromfenac concentration for fed patients was only 28% of that of fasted patients. Disregarding food intake, bromfenac 25 mg and naproxen sodium 550 mg were significantly superior to acetaminophen 325 mg for all summary measures of analgesia. Bromfenac and naproxen were superior to acetaminophen by hour 1 and this difference persisted for 8 hours. Food reduced bromfenac's analgesic effect, but not that of naproxen or acetaminophen; treatment by meal interaction was significant for five measures of efficacy. Analgesic response for fed bromfenac recipients, compared with those who were fasted, ranged from 37-71%. The percentage of patients reporting an adverse effect was significantly higher for bromfenac (25%) and naproxen (24%) than for acetaminophen (12%). CONCLUSIONS: Results of analgesic studies not taking patients' food status into consideration might be misleading. Although bromfenac 25 mg and naproxen sodium 550 mg produced significant analgesia compared with acetaminophen 325 mg, bromfenac's efficacy was significantly reduced when patients ate a standard meal. Adverse effects were transient and consistent with the pharmacologic profiles of the drugs.

A method for the 12-hour evaluation of analgesic efficacy in outpatients with postoperative oral surgery pain. Three studies of diflunisal.

We have developed a method for measuring the efficacy of a single dose of an analgesic for 12 hours after administration of outpatients with postoperative oral surgery pain. Using a self-rating record, patients evaluate their pain and its relief for 12 hours after medication. We have used this method successfully in a series of three studies to compare diflunisal, a new nonsteroidal antiinflammatory analgesic, with placebo and aspirin 650 mg, acetaminophen 600 mg, propoxyphene napsylate 100 mg, or a combination of acetaminophen with either codeine 60 mg or propoxyphene 100 mg. Diflunisal evinced an unusually long duration of analgesic effect. In each study, all doses of diflunisal were significantly superior to placebo through the end of the 12-hour observation period, while the standards were superior for periods ranging from 2 to 7 hours. In terms of peak analgesia, diflunisal 1,000 mg was comparable to the acetaminophen-codeine combination and was significantly superior to all the other analgesic standards.

Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain.

One-hundred twenty-eight outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive oral doses of ketorolac tromethamine 10 mg, aspirin 650 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. The acetaminophen-codeine combination was significantly superior to aspirin for peak analgesia. Ketorolac was significantly superior to aspirin for every measure of total and peak analgesia, and significantly superior to acetaminophen-codeine for measures of total effect. The analgesic effect of ketorolac was significant by hour 1 and persisted for 6 hours. Repeat-dose data also suggested that ketorolac 10 mg was superior to aspirin 650 mg and acetaminophen-codeine on the day of surgery. Differences among the active medications were trivial for the postoperative days 1-6 analyses. The frequency of adverse effects was over 4 times greater for acetaminophen-codeine than for ketorolac or aspirin.

Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain.

Two-hundred six outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg, ibuprofen 400 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg plus codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. All active medications were significantly superior to placebo. Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg; however, these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination. The analgesic effect of each active medication was significant by hour 1 and persisted for 5-6 hours. The data suggest a plateau in ketorolac's analgesic efficacy at the 10-mg level. Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg; ketorolac 20 mg was also superior to acetaminophen-codeine. Differences among active medications were not significant when data for the entire postoperative period (days 0-6) were evaluated. The frequency of adverse effects was similar for the active medications.

Analgesic effect of acetaminophen, phenyltoloxamine and their combination in postoperative oral surgery pain.

In this factorial study, 148 outpatients with pain after oral surgery were randomly assigned, on a double-blind basis, a single oral dose of acetaminophen 650 mg, phenyltoloxamine 60 mg, a combination of acetaminophen 650 mg with phenyltoloxamine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 6 hours after medication. Measures of total and peak analgesia were derived from these subjective reports. The acetaminophen effect was significant for every measure of total and peak analgesia. The phenyltoloxamine effect was not significant for any measure of analgesia. Although efficacy was lower for the acetaminophen-phenyltoloxamine combination than for acetaminophen alone, for every variable, the contrast for interaction was not statistically significant. The results of this study differ from those of previous studies in patients with headache and musculoskeletal pain. All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic.

Analgesic effect of fendosal, ibuprofen and aspirin in postoperative oral surgery pain.

The analgesic efficacy of a single 200-mg dose of fendosal, a nonnarcotic, nonsteroidal antiinflammatory analgesic, was compared, in a double-blind study, with aspirin 650 mg, ibuprofen 400 mg and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medicating. Each active medication was significantly superior to placebo. The peak analgesic effect of fendosal 200 mg was similar to that of the aspirin 650-mg standard. Although fendosal's onset of action was slow (3 hours), its effect persisted for 8 hours, substantially longer than that of aspirin. Ibuprofen 400 mg was statistically significantly superior to aspirin 650 mg and fendosal 200 mg for most measures of peak and total analgesia, and its effect persisted for 8 hours. The results of this study raise some questions concerning the comparability of data from studies that employ different criteria for remedication and/or different criteria for the inclusion of data in the analyses of efficacy.

Evaluation of an ibuprofen controlled-release tablet and placebo in postoperative oral surgery pain.

Seventy-four outpatients with postoperative pain after oral surgery were randomly assigned, on a double-blind basis, to receive a single oral dose of a controlled-release tablet (CRT) containing 600 mg ibuprofen, two 600-mg ibuprofen CRTs, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of total and peak analgesia were derived from these subjective reports. The ibuprofen CRTs (600 and 1200 mg) had manifested an analgesic effect by hour 1 and their efficacy persisted for 12 hours. Comparable effect for the two ibuprofen CRT dosages could suggest a plateau in analgesia at the 600-mg level or a lack of upside assay sensitivity. Duration of effect was longer for the CRTs than we have previously observed with conventional ibuprofen tablets. Adverse effects were transitory and consistent with the known pharmacologic profile of the medication evaluated.

Analgesic effect of an aspirin-codeine-butalbital-caffeine combination and an acetaminophen-codeine combination in postoperative oral surgery pain.

The efficacy of an aspirin-caffeine-codeine-butalbital combination was compared to an acetaminophen-codeine combination and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain, relief, anxiety and relaxation hourly for up to 6 hours after medicating. Each active medication was significantly superior to placebo for measures of analgesia and relaxation. Although the butalbital-containing combination provided consistently greater analgesia, the differences between active medications were not statistically significant. The acetaminophen-codeine combination significantly reduced anxiety; however, the butalbital containing combination did not. The results of this study suggest that female patients may have greater efficacy than male patients. All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic.

An evaluation of flurbiprofen, aspirin, and placebo in postoperative oral surgery pain.

One hundred sixty-four outpatients with postoperative pain after the removal of impacted third molars were randomly assigned on a double-blind basis, to receive oral doses of flurbiprofen 25, 50, or 100 mg; aspirin 600 mg; or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 8 hours after medicating. Estimates of sum of pain differences (SPID), peak pain intensity difference (PID), total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active medications were significantly superior to placebo. Analgesia was similar for flurbiprofen 25 mg and aspirin 600 mg. Flurbiprofen 50 and 100 mg were significantly superior to aspirin for every measure of analgesia except peak PID. There was a significant dose-response regression between flurbiprofen 25 mg and both of the higher dosages. Flurbiprofen 50 and 100 mg did not differ significantly, suggesting a plateau in flurbiprofen's analgesia. The analgesic effect of flurbiprofen was significant by hour 1 and persisted for 8 hours. The frequency of adverse effects was similar for the active medications.

Evaluation of bromfenac, aspirin, and ibuprofen in postoperative oral surgery pain.

Two hundred forty-one outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, to receive a single oral dose of bromfenac 5, 10, or 25 mg, aspirin 650 mg, ibuprofen 400 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief for 8 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments were significantly superior to placebo, and the slope of the dose-response curve for bromfenac was significant. Bromfenac 5 mg and aspirin 650 mg were equianalgesic; bromfenac 25 mg was slightly more efficacious than ibuprofen 400 mg. Bromfenac 25 mg and ibuprofen 400 mg were significantly superior to the other active treatments. Adverse effects were transient and consistent with the pharmacologic profiles of the medications evaluated.

Evaluation of bromfenac and ibuprofen for pain after orthopedic surgery.

STUDY OBJECTIVES: To determine the relative analgesic potency and adverse effect liability of bromfenac 25, 50, and 100 mg, and ibuprofen 200 and 400 mg in the treatment of postoperative pain after orthopedic surgery. DESIGN: Randomized, double-blind, single-dose, parallel-group relative potency assay with evaluations at 30 minutes and then at hourly intervals for up to 6 hours. SETTING: Two wards of the orthopedic surgery department at the Centralsjukhuset (Central Hospital) in Karlstad, Sweden. PATIENTS: Two hundred inpatients with steady, moderate or severe pain within 72 hours after orthopedic surgery. INTERVENTIONS: Patients received a single oral dose of bromfenac 25, 50, or 100 mg, or ibuprofen 200 or 400 mg, when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating. MEASUREMENTS AND MAIN RESULTS: The study was a valid relative potency assay with estimates of bromfenac's potency relative to ibuprofen ranging from 10.9 (nurse's global evaluation) to 16.7 (sum of hourly analog pain intensity difference scores). That is, 11-16 times the dose of ibuprofen must be administered to equal the analgesic effect of bromfenac. Patients who had eaten breakfast or lunch within 60 minutes before or 30 minutes after receiving the study medication ("fed" patients) had lower efficacy scores than those who had not ingested food within these time constraints before or after receiving the study medication ("fasted" patients). Furthermore, patients who had eaten before receiving the study medication had significantly lower efficacy scores than those who had eaten after receiving the study medication. CONCLUSIONS: The relative potency of the analgesic effect of bromfenac to ibuprofen is 11-16.7 in patients with pain after orthopedic surgery. Fed patients may have lower analgesic efficacy than fasted patients. Adverse effects for both bromfenac and ibuprofen were transient and consistent with the pharmacologic profiles of the drugs.

A 12-hour evaluation of the analgesic efficacy of diflunisal, acetaminophen, and acetaminophen-codeine combination, and placebo in postoperative pain.

The analgesic efficacy of single 500 and 1,000 mg doses of diflunisal, a new nonsteroidal antiinflammatory analgesic, was compared in a double-blind study with acetaminophen 600 mg, the combination of acetaminophen 600 mg with codeine 60 mg, and placebo in 132 inpatients with postoperative pain. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medication. Diflunisal 500 and 1,000 mg were significantly superior to placebo for every measure of total and peak analgesia, and a significant analgesic effect persisted for 8 hours. Acetaminophen alone and the acetaminophen-codeine combination were significantly superior to placebo for most measures of analgesia, and their effects were significant for 4 and 5 hours respectively. Differences among the active medications were not statistically significant for measures of total or peak analgesia.