Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain.

OBJECTIVE: The objective of this study was to demonstrate a dose-response effect with 1- and 2-tablet doses of combination hydrocodone 7.5 mg with ibuprofen 200 mg and placebo in patients with moderate to severe postoperative abdominal or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. Previous studies with this combination have demonstrated that the components have an additive analgesic effect as well as efficacy compared with other fixed-dose combination analgesics. METHODS: This randomized, parallel-group, double-blind, single-dose, placebo-controlled study compared 1 tablet of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), 2 tablets of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), and placebo (n = 60) in patients with moderate or severe pain after abdominal or gynecologic surgery. Analgesia was evaluated over 8 hours. RESULTS: Mean pain relief (PR) scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.027) and 100 (P = 0.017) minutes and at 2 (P = 0.013), 2.5 (P = 0.012), 3 (P = 0.006), 4 (P = 0.029), 5 (P = 0.002), 6 (P = 0.032), 7 (P = 0.036), and 8 (P = 0.01) hours. Mean pain intensity difference scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.013) and 100 (P = 0.007) minutes and at 2 (P = 0.003), 2.5 (P = 0.002), 3 (P = 0.002), 4 (P = 0.009), 5 (P < 0.001), 6 (P = 0.004), 7 (P = 0.009), and 8 (P = 0.001) hours. Mean total PR scores were significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.01; 0 to 4 hours, P = 0.006; 0 to 6 hours, P = 0.003; 0 to 8 hours, P = 0.003). Mean sum of pain intensity differences was significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.004; 0 to 4 hours, P < 0.001; 0 to 6 hours, P < 0.001; 0 to 8 hours, P < 0.001). Mean peak PR score and median time-to-remedication were significantly greater for the 2-tablet dose than for the 1-tablet dose (P < 0.029 and P = 0.017, respectively). Both doses were superior to placebo. There were no significant differences in the number of patients experiencing adverse events between the 2-tablet dose (n = 6 [10.0%]), the 1-tablet dose (n = 4 [6.7%]), and placebo (n = 1 11.7%]). Adverse events were not serious, and none of the patients discontinued therapy because of side effects. CONCLUSIONS: This study demonstrated that a 2-tablet dose of hydrocodone with ibuprofen provided significantly more analgesia than a 1-tablet dose (a positive dose-response effect) and that both doses were superior to placebo.

Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone and ibuprofen with that of combination oxycodone and acetaminophen in the treatment of moderate to severe postoperative obstetric or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: This randomized, double-blind, parallel-group, single-dose, active-comparator, placebo-controlled study compared the effects of a 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg with those of a 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg and placebo. Analgesia was assessed over 8 hours. RESULTS: Mean pain relief (PR) scores were similar for the hydrocodone with ibuprofen and oxycodone with acetaminophen groups (n = 61 and 59, respectively) at 0.5, 1, 1.5, 2, 2.5, 3, 4, and 7 hours and significantly greater for the hydrocodone with ibuprofen group at 5, 6, and 8 hours (P < or = 0.05). Mean pain intensity difference (PID) scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours and significantly greater for hydrocodone with ibuprofen at 5, 6, 7, and 8 hours (P < or = 0.05). Total PR scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- and 0- to 4-hour intervals and significantly greater for hydrocodone with ibuprofen for the 0- to 6- and 0- to 8-hour intervals (P < 0.05). The sum of the PID scores was similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3-, 0- to 4-, 0- to 6-, and 0- to 8-hour intervals. The median estimated time to onset of analgesia, mean peak PR score, median time to remedication, and mean global assessment score were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen. Assay sensitivity was demonstrated by the presence of statistically significant differences between both active treatments and placebo (n = 60). The number of patients experiencing adverse events was similar for each of the 3 groups (11 [18.0%], hydrocodone with ibuprofen; 7 [11.9%], oxycodone with acetaminophen; and 6 [10.0%], placebo). CONCLUSIONS: In this study, a 2-tablet dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg was as effective as a 2-tablet dose of combination oxycodone 5 mg and acetaminophen 325 mg in the treatment of moderate to severe postoperative obstetric or gynecologic pain. Both treatments were superior to placebo. The results of this study suggest that the combination of hydrocodone 7.5 mg and ibuprofen 200 mg may offer prescribers an additional option in combination pain therapy.

Analgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain.

Two randomized, double-blind, parallel-group single-dose 2 x 2 factorial analgesic studies compared a single-dose or a 2-tablet dose of a combination of 7.5 mg hydrocodone bitartrate with 200 mg ibuprofen with each constituent alone and with a placebo in women with moderate or severe postoperative pain from abdominal or gynecologic surgery. A nurse-observer recorded patient reports of pain intensity and pain relief periodically for 8 hours. In both studies, the combination was significantly superior to placebo for sum of the pain intensity differences (SPID), total pain relief (TOTPAR), peak pain intensity difference (PID) and pain relief, global evaluation, and time to remedication. The combination was likewise significantly superior to both hydrocodone and ibuprofen for most of these summary measures of analgesia. In a factorial analysis, both the hydrocodone and ibuprofen effects were significant for most summary measures of analgesia, whereas results of the interaction contrast were consistent with the concept that the analgesic effect of the combination represents the additive analgesia of its 2 constituents.

The perception of ethical dilemmas in clinical practice.

The empirical diagnosis presented in this paper is based on interviews with nurse practitioners and physicians designed to elicit their perceptions on the nature and role of ethical dilemmas in clinical practice. Having selected five of these perceptions or views which were common and significant, the philosophical therapy offered consists in, first, a general discussion of ethical dilemmas and, second, a critical analysis of each of the five views with the aim of pointing out confusions and errors, the recognition of which can be of applied and practical help in the clinical setting.

Ethical decisions with limited resources. How is that possible?

Ethical decision making is a process case managers can use to help negotiate through complicated situations. In our complex health care delivery systems, case managers often have competing benefits and burdens to balance. In this article, the author presents an ethical decision making model that can assist in the process of decision making. The obligations of case managers to patients remain constant-attempting to be of benefit, but as the trajectory of care changes from acute to chronic to dying, the understanding of benefit will change. Caring for patients and their families within a managed care environment entails always keeping the benefit of the self, patient, family, employers, and society all in balance.

Reflective action--strategies for solving client-nurse partnerships in primary care.

In this grounded theory study, which addressed the research question. 'What strategies do nurses use to form client-nurse partnerships,' a variety of data sources were used. The first data set consisted of participant observation, and reports of focus groups formed as part of the 'First International Conference on Nursing Theory and Primary Health Care' at Massey University, New Zealand which was attended by an international group of 80 nurses in 1990. As an adjunct to the formal presentations, members of the focus groups addressed four questions: a) Is a nurse-client partnership viable in primary care? b) What do you plan to do to promote this partnership? c) What do you think others should do? and d) What is the next step? Reports from these focus groups, pooled with questionnaires (n = 17) and informal interviews completed this data set. The central process that described participants' perceptions of the viability of nurse-client partnerships was named reflective action. Ethical questions arose and were placed along a continuum of viability. A second data set consisted of interviews with, and selected literature by, Canadian nurses on partnerships in primary care. The perceptions of this international study group are seen as adding to our knowledge of barriers to nurse-client partnerships in primary care, and strategies for transcending these barriers.

The do-not-resuscitate order. Moral responsibilities of the perioperative nurse.

To provide care that is consistent with a patient's view of his or her best interests, the perioperative nurse must be a knowledgeable, informed member of the OR team. This knowledge must include familiarity with and understanding of all policies that relate to the care of the surgical patient--including DNR policies. The nurse must be willing to assert his or her moral agency in developing DNR policies that will eliminate potential conflict among the OR team members regarding patients with DNR designations. Only by being a knowledgeable moral agent can the perioperative nurse function as an effective advocate of the patient as a person.

A behavioral profile of autoimmune lupus-prone MRL mice.

Manifestations of the human autoimmune disease systemic lupus erythematosus (SLE) include a number of behavioral and cognitive deficits. The present study asks whether neurobehavioral dysfunction is present also in MRL mice that spontaneously develop most of the fundamental immunological aberrations of SLE. There are two congenic substrains of MRL mice that differ in the time of disease onset: MRL-lpr mice develop lupus early and MRL(-)+/+ develop the typical signs of disease relatively late in life. The behavior of these substrains was assessed at 7 to 11 weeks of age, a time that coincides with the onset of disease in MRL-lpr mice and the absence of known lupus symptoms in the MRL(-)+/+ group. When compared to the congenic MRL(-)+/+ control substrain, MRL-lpr mice were spontaneously less active, traversed a crossbeam slower, and ceased responding to the novelty of a new environment sooner. They were also more reluctant to leave their home base or travel far away from it and perseverated in their response bias during extinction and reversal learning. Immunological status was characterized by moderate proteinuria in both substrains and high titers of antinuclear antibodies in MRL-lpr but not MRL(-)+/+ mice. Histological analysis revealed minimal or no signs of joint pathology in MRL-lpr mice. Thus, this study shows the presence of behavioral dysfunction in mice with early stages of autoimmune disease and gives support for the idea that MRL mice may provide a useful model of neurobehavioral dysfunction in SLE. It is suggested that the behavioral profile of MRL-lpr mice may indicate increased "timidity," related to genetics, autoimmunity, or both.

Effect of a social cognitive intervention on oral health status, behavior reports, and cognitions.

An intervention designed to test the influence of cognitive restructuring on protective oral health behaviors was conducted with 108 patients with mild to moderate gingivitis. Subjects in the experimental group viewed slides of active, mobile bacteria taken from their mouths on 5 occasions: before and after prophylaxis and at 3 appointments, one month apart. A specially trained hygienist discussed with these participants the process of periodontal disease, the role of bacteria, and self-efficacy (self-control) for oral hygiene self-care. Both experimental and control group subjects received instruction in oral self-care procedures. Assessments of oral health using Löe and Silness' plaque and gingival indices (PI and GI) were taken throughout the study and at 3- and 6-month follow-up visits. Self-efficacy, oral hygiene intentions, attitudes, and values comprised the set of cognition variables. Plaque and gingival indices mean differences between groups approached significance at visit 6. Analyses were also performed using percent of gingival surfaces scored at "0" (no visible bleeding on probing). A trend occurred for group differences in percent "0" scores at visit 6, with the experimental group maintaining higher percent zeros (better health) at this 3-month follow-up. At visit 7 (9-month follow-up), PI and GI differences disappeared. No significant differences were found between groups for oral health cognitions or behavior reports over time. The data suggest that the cognitive-behavioral intervention produced a delayed relapse in protective oral self-care behaviors, and by extension, oral health status. Such a delay could be clinically relevant in promoting adherence to oral hygiene behavior between professional visits.

Self-efficacy, reasoned action, and oral health behavior reports: a social cognitive approach to compliance.

The usefulness of a social cognitive approach to compliance with brushing and flossing behavior recommendations was tested with 39 patients recruited from the State University of New York at Buffalo Periodontal Disease Clinical Research Center. Participants completed mailed study instruments assessing Fishbein and Ajzen's theory of reasoned action variables, Bandura's self-efficacy variables, and frequency of brushing and flossing behavior. Results indicated positive attitudes, beliefs, and norms for brushing and flossing and positive intentions to brush but less intention to floss. Hierarchical regression analyses supported the basic usefulness of the theory of reasoned action for oral health behavior reports. Addition of self-efficacy variables to theory of reasoned action variables significantly increased the explained variance of brushing and flossing behavior reports. These results establish a strong basis for future clinical studies investigating social cognitions and the prediction of oral health behavior.

Differential regulation of insulin-like growth factor-I (IGF-I) and IGF-II release from cultured neonatal mouse calvaria by parathyroid hormone, transforming growth factor-beta, and 1,25-dihydroxyvitamin D3.

In a previous study we found that PTH stimulated bone resorption and release of insulin-like growth factor-I (IGF-I) and IGF-II from cultured neonatal mouse calvaria. Since IGF-I and IGF-II stimulate osteoblast proliferation and collagen synthesis, these results suggested that increased release of IGFs during resorption could mediate in part coupling of bone formation to bone resorption. In the present study two other osteolytic agents, transforming growth factor-beta (TGF beta) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3 were examined for effects on IGF release from neonatal mouse calvaria. Like PTH, TGF beta stimulated resorption and increased release of IGF-I and IGF-II. 1,25-(OH)2D3, however, stimulated resorption and IGF-II release comparable to PTH, but inhibited release of IGF-I. 1,25-(OH)2D3 (0.1-100 nM) inhibited basal release of IGF-I, and 10 nM 1,25-(OH)2D3 inhibited release of IGF-I induced by PTH or TGF beta. The effects of 1,25-(OH)2D3 were specific to this vitamin D metabolite and did not occur with 25-hydroxyvitamin D3 or 24,25-(OH)2D3 at the same concentration. Calcitonin (50 mU/ml) decreased 1,25-(OH)2D3 stimulation of resorption, but did not affect 1,25-(OH)2D3 stimulation of IGF-II release and inhibition of IGF-I release. This evidence that effects of 1,25-(OH)2D3 on release of the IGFs were independent of bone resorption supports the conclusion that 1,25-(OH)2D3 modulated the production and secretion of IGF-I and IGF-II in calvarial cells. The results of this and the previous study suggest that PTH, TGF beta, and 1,25-(OH)2D3 differentially regulate mouse calvarial cell IGF-I and IGF-II production.