Etoricoxib reduced pain and disability and improved quality of life in patients with chronic low back pain: a 3 month, randomized, controlled trial.

BACKGROUND: Chronic low back pain (LBP) is a growing health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat this condition, but have not demonstrated efficacy beyond 2 weeks, and no studies have shown that NSAIDs produce durable improvements in disability. METHODS: To evaluate the efficacy and durability of effect of etoricoxib for chronic LBP, a randomized, double blind, placebo-controlled trial was conducted at 46 centres. Three hundred and twenty-five patients with chronic LBP requiring treatment with an NSAID or paracetamol were randomized 1:1:1 to etoricoxib 60 mg (n=109), 90 mg (n=106), or placebo (n=110), daily for 3 months. Pre-specified endpoints over 3 months included LBP intensity scale (visual analog scale 0-100 mm) time-weighted average change from baseline, the Roland-Morris Disability Questionnaire (RMDQ), the LBP bothersomeness scale, patient and investigator global assessments, and measures of quality of life. RESULTS: Both etoricoxib groups experienced significant reductions in LBP intensity at 4 weeks versus placebo [-15.15 mm and -13.03 mm for 60 and 90 mg, respectively, probability (p)<0.001 for each], which was maintained over 3 months. Treatment resulted in significant improvement from baseline compared to placebo in RMDQ scores (etoricoxib 60 mg, -2.82 and 90 mg, -2.38, p<0.001 for each) over 12 weeks and most other efficacy endpoints. There were no significant differences between treatments in incidence of adverse events (AEs) or discontinuations due to AEs. CONCLUSION: Etoricoxib provided significant relief of symptoms and disability associated with chronic LBP detected at 1 week, confirmed at 4 weeks, and maintained over 3 months. Reductions in chronic LBP severity corresponded to improvements in physical functioning and quality of life. All treatments were generally well tolerated.

Phase III, randomized, double-blind study of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis.

BACKGROUND: Clarithromycin has an established efficacy and safety profile in the treatment of respiratory tract infections. OBJECTIVE: The purpose of this study was to compare the clinical and bacteriologic efficacy and tolerability of clarithromycin extended-release and immediate-release formulations in patients with acute exacerbation of chronic bronchitis (AECB). METHODS: In a phase III, randomized, double-blind, parallel-group, multicenter study. patients aged > or =12 years with signs and symptoms of AECB and a productive cough with purulent sputum received treatment with extended-release (two 500-mg tablets once daily) or immediate-release (one 500-mg tablet twice daily) clarithromycin for 7 days. Assessments were performed before treatment, within 48 hours after treatment, and at the test-of-cure visit (study days 19-21). Patients who took > or =1 dose of study drug were included in the safety analysis. RESULTS: Of 620 patients randomized and treated, 182 were clinically and bacteriologically assessable (100 in the extended-release group and 82 in the immediate-release group). Treatment groups were well matched with respect to demographic characteristics and medical and social history. At the test-of-cure visit, 83% (83/100) of patients in the extended-release and 82% (67/82) of patients in the immediate-release group achieved clinical cure; 86% (85/99) and 85% (70/82), respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were 86% (100/116) in the extended-release group and 88% (86/98) in the immediate-release group. The most frequently reported adverse events were diarrhea (6% in extended-release group vs 4% in immediate-release group; no significant difference), taste alterations (4% in each group), and nausea (3% in each group); no clinically meaningful changes in laboratory values or vital signs, as assessed by the investigator, were observed. CONCLUSION: This study suggests that clarithromycin extended-release and immediate-release formulations have equivalent clinical and bacteriologic efficacy and tolerability in patients with AECB.

The effect of alcohol on self-evaluation and perception of negative interpersonal feedback.

Recent theories of alcohol use and misuse assume that alcohol alters cognitive-perceptual mediating processes that indirectly reduce emotional distress. One view is that alcohol enhances perceptions of control and power. Alternatively, it has been suggested that alcohol is used to reduce self-awareness, perceptions of negative feedback and negative self-evaluations. The purpose of this study was to test these two hypotheses. Forty men, all college students, participated in the study and were randomly assigned to the four conditions in a 2 X 2 balanced placebo design. Subjects interacted with a woman confederate at two points in the procedure: first under positive feedback conditions and then, after beverage consumption, under negative feedback conditions. Both sequences were videotaped and eventually viewed by the subjects. Before and after each interaction period and after the videotape procedure, subjects completed rating forms which assessed their self-perceptions. Whereas perceptions of control and power were diminished when subjects were sober, the ratings of intoxicated subjects remained stable after they received negative interpersonal feedback. Alcohol impaired the perception of negative feedback and reduced negative evaluations of the videotaped sequences.

Alcohol, selective attention and sexual arousal in men.

Thirty-two men social drinkers were randomly assigned to the cells of a balanced placebo design to investigate the effects of expected and actual alcohol consumption on sexual responsiveness. Using a dichotic listening task, erotic and nonerotic information was presented in the nonattended channel while subjects performed simple (low-attention demand) and complex (high-attention demand) numerical tasks presented in the attended channel. Penile tumescence was recorded continuously in response to all audiotaped information. The high-attention demand task significantly interfered with sexual arousal compared with the low-attention demand task, primarily because of the significant suppressant effect of alcohol on arousal during the complex task. The lack of differences in tumescence under the two cognitive tasks when subjects were sober is inconsistent with the cognitive interference model of sexual arousal. Alcohol expectations increased arousal during the low-attention demand task, whereas actual alcohol consumption decreased arousal only during the high-attention demand task. Both effects are attributed to the different effects of these separate variables on attentional processes. The clinical implications are discussed.

Studies on avian erythrocyte metabolism. VII. Effect of inositol pentaphosphate and other organic phosphates on oxygen affinity of the embryonic and adult-type hemoglobins of the turkey embryo.

The effects of 2, 3-diphosphoglyceric acid (2, 3-DPG), adenosine triphosphate (ATP), inositol tetraphosphate (ITP), inositol pentaphosphate (IPP), and inositol hexaphosphate (IHP) on oxygen affinity of whole stripped hemoglobin (WSH), hemoglobin H (Hb-H; hatching hemoglobin), hemoglobin A (Hb-A), and hemoglobin D (Hb-D) isolated from erythrocytes (RBC) of the 25-day turkey embryo have been studied. The order of the decrease in oxygen affinity induced by these organic phosphates, at molar ratios of phosphate compound to hemoglobin (tetramer) between 2 and 4, is 2, 3-DPG less than ATP less than ITP less than IPP less than IHP. 2, 3-DPG shows a slightly greater effect on reducing oxygen affinity of Hb-H than on either adult-type hemoglobin. The effect of IPP upon lowering the oxygen affinity of either WSH, Hb-H, Hb-A, or Hb-D is approximately 20 percent less than IHP. The effects of the various organic phosphates upon the Hill constant, n, of these purified hemoglobins is variable but appears to reach a maximum when the molar ratio of organic phosphate to hemoglobin (tetramer) is 2 or greater. None of the physiologically occurring organic phosphates has a significant preferential interaction with any specific hemoglobin. These experiments strengthen and support our earlier conclusion, that the changes in whole blood oxygen affinity which occur during avian development result from the changes in composition of the intraerythrocytic organic phosphates.

Studies on avian erythrocyte metabolism. 5. Relationship between the major phosphorylated metabolic intermediates and while blood oxygen affinity in embryols and poults of the domestic turkey (Meleagris gallopavo).

The changes in organic phosphates of turkey erythrocytes (RBC) have been determined in relation to the changes in oxygen affinity of whole blood during growth of the embryo and poult. On a molar basis, 2,3 diphosphoglyceric acid (2,3-DPG) is the predominant organic phosphate of erythrocytes from turkey embryos during the last week of incubation. However, on the basis of relative % phosphate, 2,3-DPG is the major organic phosphate of the erythrocytes from turkey embryos on day 23 and 25 of incubation only. With the exception of day 23 and 25 incubation, adenosine triphosphate (ATP) represents the major organic phosphate of the erythrocytes of the turkey embryo and poult during the last week of embryonic development and through the first 29 days after hatching. The whole blood P50 during the last week of incubation and the first 8 days after hatching correlates best with the amount of ATP in the erythrocytes. The effects of inositol pentaphosphate on P50 of the whole blood is much more gradual and appears to become of major influence after 2-3 weeks post-hatching.

Susceptibility of recent isolates of Pseudomonas aeruginosa to gentamicin, polymyxin, and five penicillins, with observations on the pyocin and immunotypes of the strains.

The susceptibilities of recently isolated strains of Pseudomonas aeruginosa to gentamicin, polymyxin B, carbenicillin, ampicillin, penicillin G, and two newer penicillins were tested with the inocula-replicating technique by using undiluted and 10(-3) dilutions of the cultures. With either inoculum, polymyxin B was the most active agent, and a comparison with previous data from this laboratory showed that the susceptibility of P. aeruginosa to this antibiotic had not changed over the past 20 years. Gentamicin was nearly as active as polymyxin, all but 2 of the 141 strains tested with the diluted inoculum being inhibited by 6.25 mug/ml or less. AB-2288, an agent resembling carbenicillin, was four times more active than carbenicillin or BLP-1654; the last two were equally active against the 10(-3) inoculum. A more marked inoculum effect was noted with the penicillin analogues tested, the increase in minimum inhibiting concentration with the undiluted culture being eight-fold for carbenicillin and at least 16-fold for AB-2288 and BLP-1654. Pyocin typing and serotyping failed to demonstrate any clearly predominating types.