Transdermal fentanyl improves pain control and functionality in patients with osteoarthritis: an open-label Canadian trial.

Current treatment guidelines advocate opioids for arthritis when standard analgesics produce inadequate relief. Efficacy, adverse effects (AEs), dosing regimens, physician expertise and patient preference influence treatment selection. This study assessed transdermal fentanyl (TDF) as a treatment option for osteoarthritis (OA) patients. This prospective, Canadian open-label, 8-week trial assessed the efficacy and safety of TDF in patients with OA of hip or knee with moderate-to-severe target joint pain inadequately controlled using weak opioids. TDF was initiated at 25 mcg/h and titrated to optimal pain control. Rescue acetaminophen 500 mg was allowed (maximum 4 g/day). The main endpoint was improvement in pain control assessment rating (five rating categories); pain intensity (0-10 numerical scale), functionality (WOMAC-OA Index), health-related quality of life (SF-36 Health Survey) and global impression were also evaluated. Eighty-one patients (61% female, mean age 60 years) were enrolled; 62 were evaluable. All had failed on previous weak opioid therapy, primarily codeine or codeine combinations. At treatment end, 65% rated pain control as improved (Pain Control Assessment rating change >or=1 category; p<0.0001); mean change in pain intensity was a reduction of greater than 2 (p<0.0001); almost 50% were maintained on TDF 25 mcg/h with less than 1.3 g/day of rescue acetaminophen. At 1 month and end of treatment, changes in the SF-36 physical global scale and individual sub-scores for the pain index and role-physical scales were highly significant (p<0.0001). Improvement in functionality was noted at 1 month and at end of treatment with significant reductions in total WOMAC score, individual pain, stiffness and physical function sub-scores (p<0.0001). AEs causing discontinuation (n=32) included nausea, dizziness and vomiting. Most treatment-related AEs were mild to moderate in intensity. TDF improved pain control, functionality and health-related quality of life in these patients. The findings support current recommendations for use of opioids such as TDF as a treatment option for a sub-population of patients with OA pain.

Maintenance treatment of gastroesophageal reflux disease: an evaluation of continuous and on-demand therapy with rabeprazole 20 mg.

OBJECTIVE: To evaluate continuous therapy (COT) and on-demand therapy (ODT) with rabeprazole 20 mg for maintenance in uninvestigated gastroesophageal reflux disease (GERD). METHODS: This randomized, open-label study enrolled 331 GERD (heartburn-predominant) patients with a pre-existing proton pump inhibitor history of one month or longer, to an acute four-week trial with 20 mg rabeprazole daily for heartburn management. Patients who achieved satisfactory heartburn control during the acute phase (three days or less of heartburn, with no more than one episode rated as moderate, and heartburn rated satisfactorily or completely controlled with minimal rescue antacid use in the seven days preceding randomization) were randomly assigned to six months of rabeprazole 20 mg given as either daily COT or daily ODT, which was initiated upon symptom recurrence and stopped upon symptom resolution. Rescue antacid usage was permitted and tracked. Primary efficacy was measured as the proportion of heartburn-free days over six months. RESULTS: For the 268 patients, the mean percentage of heartburn-free days for the COT group and for the ODT group were 90.3%+/-14.8% and 64.8%+/-22.3%, respectively (P<0.0001). COT was associated with an increased number of medication intake days (154+/-40.2) versus ODT (68+/-46.1), with less heartburn episodes observed with COT versus ODT, respectively (n=7, n=26, P<0.0001). Ninety-two per cent of COT patients and 79% of ODT patients were either 'satisfied' or 'very satisfied' with treatment. The mean usage of antacids was low and similar in both groups. COT and ODT regimens were safe and well-tolerated, with a similar incidence of adverse events. CONCLUSION: Results based on symptom assessments favour COT with rabeprazole 20 mg for maintenance therapy in patients with uninvestigated GERD; however, both therapy types are safe and acceptable treatment options for selected patients.

Chronic pain in Canada: have we improved our management of chronic noncancer pain?

BACKGROUND: Chronic noncancer pain (CNCP) is a global issue, not only affecting individual suffering, but also impacting the delivery of health care and the strength of local economies. OBJECTIVES: The current study (the Canadian Chronic Pain Study II [CCPSII]) was designed to assess any changes in the prevalence and treatment of CNCP, as well as in attitudes toward the use of strong analgesics, compared with a 2001 study (the CCPSI), and to provide a snapshot of the current standards of care for pain management in Canada. METHODS: Standard, computer-assisted telephone interview survey methodology was applied in two segments, ie, a general population survey and a survey targeting randomly selected primary care physicians (PCPs) who treat moderate to severe CNCP. RESULTS AND DISCUSSION: The patient-reported prevalence of CNCP within Canada has not markedly changed since 2001 but the duration of suffering has decreased. There have been minor changes in regional distribution and generally more patients receive medical treatment, which includes prescription analgesics. Physicians continue to demonstrate opiophobia in their prescribing practices; however, although this is lessened relating to addiction, abuse remains an important concern to PCPs. Canadian PCPs, in general, are implementing standard assessments, treatment approaches, evaluation of treatment success and tools to prevent abuse and diversion, in accordance with guidelines from the Canadian Pain Society and other pain societies globally, although there remains room for improvement and standardization.

Oral rabeprazole vs. intravenous pantoprazole: a comparison of the effect on intragastric pH in healthy subjects.

BACKGROUND: Intravenous pantoprazole is often administered inappropriately to hospitalized patients who can take oral medications. AIM: To compare the antisecretory effects of oral rabeprazole and intravenous pantoprazole in healthy subjects. METHODS: In a double-blind, double-dummy, two-way crossover study, 38 Helicobacter pylori-negative volunteers were randomized to oral rabeprazole 20 mg or intravenous pantoprazole 40 mg daily for 3 days followed, after a 14-day washout period by the comparator treatment. Intragastric pH was recorded continuously for 24 h at baseline and on days 1 and 3 of each treatment period. RESULTS: The mean (95% CI) percentage of the 24-h recording with gastric pH >4 was higher with rabeprazole than with pantoprazole on day 1: 37.7% (30.6-44.8%) vs. 23.9% (20.0-27.8). The mean percentage times with pH >3 and >4 for all intervals assessed were greater and the median 24-h intragastric pH values were higher with rabeprazole than with pantoprazole on days 1 and 3. The mean acidity index was lower with rabeprazole on days 1 and 3. CONCLUSIONS: Oral rabeprazole 20 mg produced greater acid suppression than intravenous pantoprazole 40 mg. Therefore, it may be an appropriate and effective alternative in patients who can take oral medication.

Relative abuse potential of opioid formulations in Canada: a structured field study.

INTRODUCTION: While prescription opioids can improve quality of life through pain relief they are susceptible to misuse. This field study characterizes the relative susceptibility and attractiveness of a new analgesic patch, with fentanyl embedded in a matrix material, compared to other opioid dose formulations. METHODS: Recreational opioid abusers (N = 42; 31 male, 1 female)from three Canadian sites participated in structured interviews. They were presented with nine products, some of which were hypothetical (fentanyl [F], hydromorphone [H], and oxycodone [O] in each of three formulations: matrix patch [M], reservoir-type gel patch [G], and tablet [T]). The attractiveness and tampering potential of each product was ranked using two 7-point Likert scales (Value of Product and Likelihood to Tamper), an index representing the product of the two scales, a 17-item Opiate Attractiveness Scale (OAS), relative street value, and rank order of overall desirability. Non-parametric analyses were used to compare each product to the FM. RESULTS: The FT, HT, and FM were highly valued and most likely to be tampered with. The products were ranked in decreasing order of desirability as follows: FT > HT > FM > FG > OT > HM > HG > OM > OG. On the OAS, FM was more attractive than all gel-patch products (p < 0.001), and OT was most attractive overall. FM was statistically similar to OT, FT, OM, and HT. Of the 42 subjects, 25 (60 percent) preferred the matrix patch to the gel patch. Of the 17 subjects who preferred the gel patch, 10 (59 percent) were from a region generally unfamiliar with that formulation. CONCLUSIONS: Fentanyl is attractive to opioid abusers regardless of formulation. In Canada, a fentanyl matrix patch may be at higher risk for diversion, tampering, and abuse than other transdermal opioid formulations. These findings should be confirmed by epidemiological studies. Comparative risk management programs should be part of the development of any new narcotic delivery system.

Preference for and satisfaction of Canadian women with the transdermal contraceptive patch versus previous contraceptive method: an open-label, multicentre study.

OBJECTIVE: To document Canadian women's experience with the transdermal contraceptive patch, a method delivering 150 microg norelgestromin and 20 microg ethinyl estradiol daily. METHODS: We conducted an open-label, multicentre, descriptive cohort study of the contraceptive patch over 9 cycles in 392 women requiring contraception. A single treatment cycle consisted of 3 consecutive 7-day patch applications followed by 1 patch-free week. At the final visit, overall satisfaction and preference for the patch was rated and compared with the previously used contraceptive method. RESULTS: At baseline, 80.9% of participants were either very satisfied or somewhat satisfied with their previous contraceptive method, 89% having used oral contraceptives. At final observation, 60.6% of participants preferred the patch, 9.3% had no preference; and 30% preferred their previous method (n = 376). A total of 279 participants (71.2%) completed 9 cycles of patch use. Of these, 91% were satisfied with the patch and 74.9% preferred the patch to their previous contraceptive (43% strongly preferred and 31.9% preferred); 9% had no preference; and 16.1% preferred their previous method. Of those who preferred the patch, 82.7% preferred it because of its convenience or simplicity. Across all cycles, 88% of participants recorded perfect compliance. The most common adverse event was application site reactions (most of which were mild), experienced by 49% of participants: 33.7%, 16.5%, and 14.7% at cycles 1, 4, and 9, respectively. CONCLUSION: Both preference for and satisfaction with the transdermal contraceptive patch were high. Most participants.

Efficacy and safety of transdermal fentanyl and sustained-release oral morphine in patients with cancer and chronic non-cancer pain.

PURPOSE: To evaluate effectiveness and safety information of transdermal fentanyl (TDF) (Duragesic/Durogesic) and sustained-release oral morphine (SRM) in cancer pain (CP) and chronic non-cancer pain (NCP), a pooled analysis was conducted on datasets of published, open label, uncontrolled (no comparator group) and randomised controlled (with SRM as comparator) studies of TDF. PATIENTS AND METHODS: Eight trials with treatment durations of at least 28 days met the inclusion criteria. The effectiveness analysis assessed changes in average pain and pain 'right now' scores between baseline and Day 28. The safety analysis evaluated the incidence of adverse events (AEs) reported within the first 28 days of treatment with TDF or SRM. Subgroup analyses included pain type, gender, age, weight, and body mass index. RESULTS: Pooled efficacy data were available from 1220 patients; these showed that both TDF and SRM were effective in improving pain 'right now' scores (0-100 scale) from baseline to Day 28. The improvement was significantly more pronounced in the TDF treatment group (-26.7 +/- 31.3 for TDF, -18.7 +/- 30.9 for SRM, p = 0.002). This favourable effect of TDF was most apparent amongst patients with NCP. Data concerning AEs were available from over 2500 patients with CP (3 out of 10 patients) or chronic NCP (7 out of 10 patients). Significantly fewer patients in the TDF than in the SRM group reported any AE (72% vs. 87% respectively; p < 0.001), or an AE leading to the study drug being permanently discontinued (16% vs. 23% respectively; p < 0.001). Constipation and somnolence occurred considerably less frequently in the TDF than in the SRM treatment group. This difference was statistically significant in both the CP and NCP subgroups. CONCLUSION: This pooled data analysis provides expanded insight into the safety and effectiveness profile of transdermal fentanyl in patients with chronic pain. It shows significantly improved pain relief with transdermal fentanyl compared with sustained-release oral morphine, and supports current evidence of favourable tolerability of transdermal fentanyl, particularly with regard to reduced constipation and somnolence.

Double-blind comparison of carbetocin versus oxytocin in prevention of uterine atony after cesarean section.

OBJECTIVE: The goal of this study was to compare carbetocin, a long-acting oxytocin analog, with oxytocin in the prevention of uterine atony after cesarean section. STUDY DESIGN: We enrolled 694 patients undergoing elective cesarean section in a Canadian multicenter, double-blind, randomized clinical trial. We compared the effect of a single 100 microg dose of carbetocin with that of a standard 8-hour infusion of oxytocin. The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony. A variable sample size, sequential design was used. RESULTS: The overall oxytocic intervention rate was 7.4%. The odds of treatment failure requiring oxytocic intervention was 2.03 (95% confidence interval 1.1 to 2.8) times higher in the oxytocin group compared with the carbetocin group, respectively, 32 of 318 (10.1%) versus 15 of 317 (4.7%), P <.05. CONCLUSIONS: Carbetocin, a new drug for the prevention of uterine atony, appears to be more effective than a continuous infusion of oxytocin and has a similar safety profile.

Double-blind, randomized comparison of the effect of carbetocin and oxytocin on intraoperative blood loss and uterine tone of patients undergoing cesarean section.

OBJECTIVES: A double-blind randomized study involving pregnant women undergoing cesarean section was conducted to compare the effectiveness of a single 100 micrograms intravenous injection of the long-acting oxytocin analog, carbetocin, with that of a standard infusion of oxytocin with respect to intraoperative blood loss. The two treatments also were compared for safety and ability to maintain adequate uterine tone. STUDY DESIGN: The study drug was administered to 57 women during elective cesarean section after placental delivery; blood was collected until abdominal closure. Intraoperative blood loss was calculated with a sensitive colorimetric method. Position, tone of the fundus, and vital signs were assessed up to 24 hours after the operation. The need for additional uterotonic agents was recorded. RESULTS: A single 100 micrograms intravenous injection of carbetocin was as effective as a continuous 16 hour infusion of oxytocin in controlling intraoperative blood loss after placental delivery. Mean blood loss after carbetocin administration was 29 ml less than after oxytocin administration (p = 0.3). Subset analysis deleting two patients who received oxytocic intervention in the operating room and one extreme outlier revealed a mean blood loss of 41 ml less in the carbetocin group (p = 0.14) with lower variances (p = 0.02). The percentage of patients with blood loss of 200 ml or less was greater with carbetocin (79% vs 53%; p = 0.041). Carbetocin enhanced early postpartum uterine involution. The fundus was below the umbilicus in more patients who received carbetocin at 0, 2, 3, and 24 hours on the ward (p < 0.05). There were no significant differences in uterine tone or type or amount of lochia. Additional oxytocin was used to treat three patients for postpartum hemorrhage or persistent uterine atony. All interventions were in the oxytocin group. Vital signs and hematologic values were comparable in each group, confirming similar safety profiles. CONCLUSIONS: A single 100 micrograms intravenous injection of carbetocin is as effective and more reliable than a standard continuous infusion of oxytocin in maintaining adequate uterine tone and preventing excessive intraoperative blood loss during cesarean section after delivery of the placenta. Patients receiving carbetocin required less intervention. Carbetocin was well tolerated.

Transfer of carbetocin into human breast milk.

OBJECTIVE: To study the transfer of carbetocin into human breast milk. METHODS: Five healthy nursing women, 7-14 weeks postpartum, emptied their breasts using a breast pump and then received 70 micrograms carbetocin by intramuscular injection. Using a radioimmunoassay, the concentrations of carbetocin were measured in plasma and breast milk samples obtained before carbetocin administration and at 15, 30, 60, 90, 120, and 240 minutes after drug administration. RESULTS: For plasma, the mean (+/- standard deviation) area under the curve (AUC) of carbetocin versus time was 1119.3 +/- 315.9 pg/mL, a value about 50 times higher than the mean AUC for carbetocin in breast milk (18.6 +/- 13.7 and 29.0 +/- 23.8 pg/mL for the right and left breast, respectively). The ratio of milk to plasma AUC was low: 1.7 +/- 0.9 and 3.1 +/- 2.8% for the left and right breast, respectively. No serious adverse reactions occurred and no clinically significant changes in vital signs were found. CONCLUSION: Very little carbetocin is transferred into human breast milk, presenting little risk to breast-fed infants.

Multiple follicular recruitment and intrauterine insemination outcomes compared by age and diagnosis.

We studied the outcome of our intrauterine insemination (IUI) programme, evaluating female age and diagnosis. One-hundred-and-twenty-six patients less than 36 years of age (mean 30.91 +/- 3.02 years) completed 306 cycles of multiple follicular recruitment (MFR) and timed IUI; 64 patients greater than or equal to 36 years of age (mean 38.36 +/- 2.08 years) completed 166 cycles (total 190 patients, 472 cycles). The male partners' semen was prepared for IUI with wash and swim-up techniques. Diagnostic groups were: male factor (n = 26), idiopathic (n = 33), endometriosis (n = 19), ovulatory disorder (n = 7), other (n = 19) and combined factors (n = 86). Pregnancy rates (% per couple, % per cycle) [overall (31.58, 12.7)] [less than 36 years (38.10, 15.69)] [greater than 36 years (18.75, 7.23)] were greater in the less than 36 years group (P less than 0.025). The probability of conception after three treatment cycles was 0.402 overall, 0.481 for age less than 36 years and 0.252 for age greater than or equal to 36 years. The probability of conception for male factor and idiopathic infertility patients was 0.469 and 0.411 respectively. An age effect was found on pregnancy rates in the idiopathic group only. In conclusion, MFR + IUI is a valuable treatment especially for male factor patients and patients less than 36 years old, with idiopathic infertility.