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CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Double-blind comparison of an acetaminophen-codeine-caffeine combination in oral surgery pain.

The purpose of this paper was to evaluate the contribution of low dosages of codeine and caffeine when added to acetaminophen. Subjects were dental outpatients undergoing oral surgery involving bone removal. This was a single-dose, parallel group, double-blind assay evaluting 99 subjects. The treatment groups were acetaminophen 1000 mg, acetaminophen 1000 mg + codeine 16 mg + caffeine 30 mg and placebo. The results demonstrated that both active treatments were superior to placebo. Overall, the combination was slightly better than acetaminophen alone. The advantage of the combination appeared more evident in the "severe" baseline pain group.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Comparative study of ibuprofen lysine and acetaminophen in patients with postoperative dental pain.

This single-dose, double-blind, parallel-group, single-site study compared ibuprofen lysine 400 mg with acetaminophen 1000 mg and placebo in 240 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, overall analgesic efficacy, duration of effect, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, need for additional analgesic medication, and patient global evaluation. Both ibuprofen lysine 400 mg and acetaminophen 1000 mg were significantly (P < or = 0.05) more effective than placebo. Ibuprofen lysine had a significantly (P < or = 0.05) faster onset of action with greater peak and overall analgesic effect than did effect than did acetaminophen. All treatments were generally well tolerated.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Time to onset of analgesia and analgesic efficacy of effervescent acetaminophen 1000 mg compared to tablet acetaminophen 1000 mg in postoperative dental pain: a single-dose, double-blind, randomized, placebo-controlled study.

This randomized, double-blind, placebo-controlled study compared the time to onset of analgesia and the analgesic efficacy of two formulations of acetaminophen 1000 mg--an effervescent solution and tablet--in 242 patients with moderate or severe pain following dental surgery. Onset of analgesia was determined using a two-stopwatch procedure. Analgesia was assessed over a 4-hour period. Treatments were compared using standard indexes of pain intensity and pain relief and summary measures. Both acetaminophen formulations were significantly more effective than their corresponding placebo for all efficacy assessments. The median time to onset of analgesia was significantly shorter with effervescent acetaminophen (20 minutes) compared to tablet acetaminophen (45 minutes). During the first 45 minutes after administration, effervescent acetaminophen was significantly more effective at each scheduled assessment time than tablet acetaminophen. The median time to meaningful pain relief was significantly shorter with effervescent acetaminophen (45 minutes) compared to tablet acetaminophen (60 minutes). At 4 hours after administration, the pain relief was significantly better with tablet acetaminophen than with effervescent acetaminophen. No other significant differences were observed between the active treatments. In conclusion, effervescent acetaminophen produces a significantly faster onset of analgesia than tablet acetaminophen.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

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.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

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.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Combining paracetamol with a selective cyclooxygenase-2 inhibitor for acute pain relief after third molar surgery: a randomized, double-blind, placebo-controlled study.

Severe pain after third molar surgery is often encountered and more effective treatment regimes are warranted. The objective of this study was to evaluate if the combination of paracetamol and rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, improves analgesic effects following third molar surgery compared with rofecoxib alone. Paracetamol alone was also evaluated. Altogether 120 patients with moderate to severe pain after third molar surgery were given a single postoperative dose of one of the following treatments: rofecoxib + paracetamol; rofecoxib alone; paracetamol alone; or placebo. Patients assessed level of pain and pain relief every 30 min for 8 h after surgery, and made a global evaluation of the medication 4 and 8 h after surgery. Paracetamol and rofecoxib combined improved the analgesic effect compared with rofecoxib alone for the first 1.5 h. Rofecoxib alone and the combination of paracetamol and rofecoxib had a significantly better analgesic effect than paracetamol alone from 3 h onwards. The early onset of pain relief for the combination of paracetamol and rofecoxib, compared with rofecoxib alone, could be of great importance when treating acute pain after third molar surgery. After data collection for this study, rofecoxib was withdrawn from the market as a result of reported fatal cardiovascular events. Whether this is relevant for short-term use is unknown, but it has to be considered before rofecoxib may be used for pain relief following third molar surgery.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Bromfenac, acetaminophen, and placebo in orthopedic postoperative pain.

In a double-blind, placebo-controlled, single-dose, parallel-group study, oral doses (5, 10 and 25 mg) of the prostaglandin synthetase inhibitor bromfenac were compared with acetaminophen (1000 mg) and placebo for postoperative orthopedic pain. Analgesic measurements were made by nurse observers by use of standard verbal rating and visual analog scales. For most pain intensity and pain relief measurements, 1000 mg acetaminophen was statistically superior to placebo, demonstrating assay sensitivity, and 10 and 25 mg doses of bromfenac were statistically better than both placebo and 5 mg bromfenac for ordinal and analog ratings of pain intensity and pain relief; 25 mg bromfenac produced significantly longer time to remedication than acetaminophen. The 5 mg dose of bromfenac was statistically superior to placebo for some measures, including remedication time. There were no untoward adverse effects or alterations in vital signs. Overall, 10 mg bromfenac produced analgesia equivalent to that of 1000 mg acetaminophen in this pain context.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

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.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

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.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain.

Ibuprofen is a peripherally acting nonsteroidal anti-inflammatory drug indicated fo ranalgesia, antipyresis, and various arthritic conditions. A solubilized 200 mg liquigel formulation of ibuprofen has been shown to have a more rapid rate of absorption compared with ibuprofen 200 mg tablets. Ibuprofen liquigels have a kinetic profile similar to ibuprofen suspension, with both a higher Cmax and an earlier tmax than any solid tablet. The objective of this single-dose, double-blind, triple-dummy, parallel-group study was to assess the time to onset of relief and overall analgesic efficacy of liquigel ibuprofen 400 mg, ketoprofen 25 mg compared with acetaminophen 1000 mg, and placebo in 239 patients with moderate or severe pain following third molar extractions. Treatments were compared over 6 hours using standard scales for pain intensity and relief and stopwatch onset of meaningful relief. All active treatments provided meaningful relief significantly faster compared with placebo. Ibuprofen provided significantly faster relief compared with acetaminophen and ketoprofen. By the end of the study (6 h), onset of meaningful relief was achieved by 36%, 99%, 96%, and 88% of the patients in the placebo, ketoprofen, ibuprofen, and acetaminophen groups, respectively. The median times to onset of relief were > 6 hours for placebo, 25.5 minutes for ketoprofen, 24.2 minutes for ibuprofen, and 29.9 minutes for acetaminophen. In addition, both ibuprofen and ketoprofen showed statistical superiority over acetaminophen at earlier time points on the time-effect curves for pain relief and pain intensity difference. Consistent results were seen with respect to the 6-hour summary efficacy variables: the three active treatments were significantly better than placebo, and ibuprofen was significantly better than both acetaminophen and ketoprofen. Liquigel ibuprofen 400 mg was shown to provide faster relief and superior overall efficacy compared with ketoprofen 25 mg, acetaminophen 1000 mg, and placebo. No serious adverse effects were reported in this single-dose study.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Evaluation of piroxicam-beta-cyclodextrin, piroxicam, paracetamol and placebo in post-operative oral surgery pain.

Two hundred ninety-eight patients with post-operative pain after the surgical removal of an impacted third molar were randomly assigned, on a double-blind basis, to receive a single oral dose of piroxicam 20 mg, or piroxicam-beta-cyclodextrin equivalent to 20 mg piroxicam, or paracetamol 500 mg, or placebo. Using a semi-quantitative self-rating scale, patients rated their pain and its relief at 30-min intervals for the first 2 h, and then hourly for 4 h after treatment administration. All active medications were reported to be significantly superior to placebo. The three active drugs were comparable for the degree of analgesia up to the third hour, after which the effect of paracetamol decreased significantly as compared to piroxicam-beta-cyclodextrin and piroxicam. Piroxicam-beta-cyclodextrin and paracetamol were more rapid than piroxicam in inducing analgesia. The tolerability for the active drugs was comparable to that for placebo.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Evaluation of oxycodone and acetaminophen in treatment of postoperative dental pain.

Although both acetaminophen and oxycodone are commonly used analgesics, they were not available as a combination until recently. Since oxycodone is not available as a single entity, there is no archival or even anectodal information on the efficacy and safety of this combination. The purpose of this study was to evaluate the relative efficacy of various doses of the combination that could be used in dental situations. The single-dose efficacy and safety of acetaminophen 500 mg., oxycodone 5 mg., acetaminophen 500 mg. + oxycodone 5 mg., acetaminophen 1,000 mg. + oxycodone 5 mg., acetaminophen 1,000 mg. + oxycodone 10 mg., and placebo were compared in outpatients who experienced moderate to severe pain after surgical removal of inpacted third molars. Analgesic data were analyzed by analysis of variance and Duncan's multiple range test. All active treatments were superior to placebo, with the high-ratio combination being the most efficacious. This treatment also had the highest incidence of limiting side effects. A positive dose-effect relationship was evident for both acetaminophen 500 mg. and 1,000 mg. and for oxycodone 5 mg. and 10 mg.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Paracetamol, tiaramide and placebo for pain relief after orthopedic surgery.

Eighty patients took part in this double-blind, single-dose group-comparative study, comparing the analgesic efficacy of tiaramide hydrochloride 100 mg and 200 mg, paracetamol 1000 mg, and placebo for pain after orthopedic operations. The four treatment groups were similar on entry to the trial. Pain relief was assessed up to 6 h after treatment, using a visual analogue pain scale and a pain score, both giving similar results. Statistically significant pain relief (mean pain intensity differences and sum of pain intensity differences) was seen in the group receiving paracetamol compared to those receiving placebo or tiaramide from 1 h to 6 h after drug ingestion. There was no significant difference between placebo and tiaramide 100 or 200 mg. No adverse reactions were reported.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Additive analgesic effect of codeine and paracetamol can be detected in strong, but not moderate, pain after Caesarean section. Baseline pain-intensity is a determinant of assay-sensitivity in a postoperative analgesic trial.

A randomized, double-blind, placebo-controlled single oral dose study was done in order to examine whether codeine has an additive analgesic effect to that of paracetamol for moderate and strong postoperative pain after abdominal surgery. The maximum recommended single dose of paracetamol 1000 mg (Paracet) was compared with a combination of a submaximal dose of paracetamol 800 mg plus codeine 60 mg (Paralgin forte) and placebo for pain relief after Caesarean section in 125 patients. Visual analogue pain intensity score (VAS 0-100 mm) and categorical pain relief score were recorded for 6 hours after the study drug intake. The main efficacy variables analyzed were: pain intensity difference and summed pain intensity differences during the first 3 and 6 h after study drug intake, total pain relief during the first 3 and 6 h, global evaluation score at the end of the observation period, and time to rescue analgesic. Because of protocol violations, 17 patients were excluded from the analysis of effects. Among the 108 patients included in the analysis of analgesic effect, 49 patients had moderate baseline pain (VAS between 40 and 60 mm on a 100 mm scale), and 59 patients had strong baseline pain (VAS more than 60 mm). In patients with strong baseline pain, statistically highly significant differences were documented in efficacy variables between the active drugs and placebo and between the two active drugs. However, in patients with moderate baseline pain, no differences were found between the study drugs in any of the analgesic efficacy variables. This study thus confirms that codeine has additive analgesic effect to paracetamol in pain after surgery. Our results show the importance of initial pain intensity in postoperative assessment of analgesic drugs. Assay-sensitivity and test power are increased by selecting patients with sufficiently high initial pain intensity and by comparing groups of patients with identical surgery and similar demographic variables.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Analgesic efficacy of flurbiprofen in comparison with acetaminophen, acetaminophen plus codeine, and placebo after impacted third molar removal.

The analgesic efficacy of 50 and 100 mg flurbiprofen was compared with acetaminophen 650 mg, acetaminophen 650 mg plus codeine 60 mg, and placebo. Subjects undergoing the surgical removal of impacted third molars were randomly administered one of the five treatments after the onset of moderate to severe postoperative pain. Pain intensity, pain relief, and side effects were evaluated for 6 hours after drug administration. Both doses of flurbiprofen resulted in significant analgesia in comparison with placebo, acetaminophen, and acetaminophen plus codeine as measured by pain intensity difference, pain relief, and global evaluation. The greatest incidence of side effects occurred in the group receiving acetaminophen plus codeine, and the fewest side effects were reported by subjects administered flurbiprofen. The results of this study indicate that flurbiprofen is more effective and causes fewer effects than acetaminophen and codeine when used for post-operative dental pain, in ambulatory patients.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

A controlled comparative evaluation of acetaminophen and aspirin in the treatment of postoperative pain.

The analgesic effects of acetaminophen (1 gm), aspirin (650 mg), and placebo were evaluated in a double-blind, randomized parallel study. The subjects were 162 outpatients who had experienced moderate or severe pain as a result of dental surgery involving bone removal. Patients evaluated the intensity of their pain and the extent of their relief from pain at 30 minutes, at one hour, and at each subsequent hour for six hours after the administration of the study medication. During the six-hour period, 135 of the 162 patients were remedicated. At the end of the six-hour period each patient assessed overall treatment. Two measures of analgesia were derived from patients' evaluations of the intensity of pain, and three other measures were derived from evaluations of relief from pain. On all six measures used, the groups receiving acetaminophen and aspirin reported analgesic effects significantly superior (P less than 0.05) to those of placebo. Acetaminophen was significantly better than aspirin with respect to the maximum difference in the intensity of pain (P less than 0.05) and the maximum pain relief achieved (P less than 0.03) and according to the global evaluation (P less than 0.02). These differences were most striking in patients with severe initial pain.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Analgesic efficacy and safety of (R)- ketoprofen in postoperative dental pain.

This double-blind, randomized, parallel-group study compared the analgesic efficacy and safety of single doses of (R)- ketoprofen 25 mg and 100 mg to that of acetaminophen 1,000 mg and placebo in 177 patients experiencing moderate to severe pain after surgical removal of their impacted third molars. Both (R)- ketoprofen 100 mg and acetaminophen 1,000 mg were significantly (P < 0.05) more efficacious than placebo for all summary analgesic measures. Other than a more rapid analgesic onset (45 minutes versus 60 minutes) for acetaminophen 1,000 mg, (R)- ketoprofen 100 mg and acetaminophen 1,000 mg were statistically equivalent to each other. The 25 mg dose of (R)- ketoprofen appeared to approach the analgesic threshold dose, being numerically but not statistically superior to placebo for all summary measures. There were no serious adverse events observed in this study, with the overall incidence of side effects being somewhat less in the (R)- ketoprofen groups than in the acetaminophen 1,000 mg group. (R)- Ketoprofen possesses analgesic activity and an acceptable side-effect profile in the oral surgery pain model.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Analgesic combinations with orphenadrine in oral post-surgical pain.

Two hundred male and female patients underwent a variety of oral surgical procedures and were treated afterwards in four test groups. They took a combination of orphenadrine (25 mg) and acetaminophen (325 mg), either drug alone, or placebo. A double-blind study design was used. All patients had moderately severe baseline pain intensity; post-treatment pain relief was recorded at 30 minutes, one, two, four and six hours. A back-up analgesic (codeine-ASA) was made available if needed. Pain intensity difference (PID) and sums of pain intensity difference (SPID) were calculated using established analgesic study techniques. Statistical analyses indicated better analgesic efficacy in both PID and SPID scores for the orphenadrine-acetaminophen combination over the three other treatments. This was evident at 30 minutes and continued through the sixth hour. Each active drug, in turn, was also significantly better throughout than placebo for pain relief. Sub-groups in each treatment regimen required additional pain relief prior to six hours, with significantly more placebo than orphenadrine-acetaminophen patients needing remedication. Side-effect incidence was very low and randomly distributed among the four groups.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

A single-dose, double-blind comparison of naproxen sodium, acetaminophen, and placebo in postoperative dental pain.

The analgesic efficacy and duration of action of naproxen sodium 440 mg (n = 92), acetaminophen 1000 mg (n = 89), and placebo (n = 45) were compared in a single-dose, randomized, double-blind, 12-hour study of patients with at least moderate pain secondary to extraction of three or four third molars. Time to remedication, a measure of duration of analgesic effect, was significantly longer (P < 0.001) with naproxen sodium (median, 9.9 hours) than with either acetaminophen (median, 3.1 hours) or placebo (median, 2.0 hours). Naproxen sodium was also superior to acetaminophen for peak pain intensity difference (visual analog scale), summed pain intensity differences, total pain relief, peak pain relief, time to reduction of pain by 50%, and overall rating. The overall percentages of patients reporting adverse events, and the types of events reported, were comparable with the three treatments. Thus naproxen sodium demonstrated superior efficacy and similar tolerability to acetaminophen in this postoperative dental pain model.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine.

In a single-dose, parallel group, randomized block treatment allocation study, the relative analgesic efficacy of flurbiprofen, a nonsteroidal antiinflammatory drug, was compared to acetaminophen 650 mg with codeine 60 mg, zomepirac sodium 100 mg, and placebo. A total of 226 post-surgical dental patients (146 females and 80 males) participated in the study. Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination. The results of this study support previous work on flurbiprofen.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Effect of caffeine on acetaminophen analgesia.

Our objective was to determine the value of caffeine in combination with acetaminophen in the relief of pain from uterine cramping, episiotomy, and third molar extraction. In the dental study, 173 patients received two or four tablets of 500 mg acetaminophen or the combination of 500 mg acetaminophen and 65 mg caffeine. In the three postpartum studies, 1345 patients received one, two, or three tablets of acetaminophen, the combination, or a placebo. The mean scores for the summary variable percent sum of the pain intensity differences (% SPID) were higher in all for the combination than for acetaminophen alone, and in two studies the null hypothesis of no differences was rejected. The relative potency estimates for % SPID were 1.9, 1.8, and 1.3 for the three studies in which bioassays could be performed and the pooled relative potency was 1.7 with a 95% confidence interval of 1.1 to 3.1. The results were essentially the same among pain models and among patient groups with similar habitual caffeine consumption. Onset of analgesia was also faster with the combination. We conclude that caffeine enhances the analgesic efficacy of acetaminophen.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Comparison of oral nalbuphine, acetaminophen, and their combination in postoperative pain.

This double-blind, randomized, parallel, placebo-controlled study evaluated the analgesic effects of single oral doses of 30 mg nalbuphine, 650 mg acetaminophen, and the contribution of each to the efficacy of their combination in 128 hospitalized patients with postoperative pain. Subjective reports of patients evaluated each hour for 6 hours were used as indices of analgesic response. Both nalbuphine and acetaminophen were significantly superior to placebo for most measures of total and peak analgesia. The interaction contrast between nalbuphine and acetaminophen was not significant for any analgesic measurements, indicating an additive effect of the components. The combination was the most effective treatment, followed by nalbuphine, acetaminophen, and placebo. Effects of the combination were significantly different from those of acetaminophen at 4, 5, and 6 hours and from those of placebo at 1 to 6 hours. There was no significant difference in the frequency or intensity of side effects among the groups. The combination of nalbuphine and acetaminophen appears to be a therapeutically useful combination.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Ketoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain.

Ketoprofen (Orudis) is a nonsteroidal anti-inflammatory drug that is currently approved in the United States for the management of mild to moderate pain. The objective of this trial was to determine the effectiveness of orally administered ketoprofen in the management of severe postoperative pain. This randomized, double-blind parallel study compared the efficacy and safety of single doses of 100 mg or 50 mg ketoprofen, the combination of 650 mg acetaminophen plus 10 mg oxycodone hydrochloride, 650 mg acetaminophen, or placebo in 240 patients with severe postoperative pain after cesarean section. Analgesia for the first dose was assessed over an 8-hour period. Multiple doses of 100 mg or 50 mg ketoprofen and the combination at half the dose (325 mg acetaminophen plus 5 mg oxycodone) were also assessed for up to 7 days. The 100 and 50 mg doses of ketoprofen and the combination were statistically superior to acetaminophen and placebo for many analgesic measures. A dose response was observed between the two doses of ketoprofen, with the 100 mg dose providing significantly greater analgesia over the lower dose. Ketoprofen, 100 mg, was at least as effective as the combination and its effects lasted longer, with the exception of hour 1 when the combination was superior. Remedication time for the group receiving 100 mg ketoprofen was significantly longer than for the other treatment groups. Significantly more patients who took repeated doses of the combination (84%) than those who took either dose of ketoprofen (70%) had adverse effects. Ketoprofen at both dose levels was shown to be effective, long-lasting, and well tolerated, and it should be considered as a viable option for the management of moderate to severe postoperative pain.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

[The efficacy of paracetamol (Tylenol) and acetyl salicylic acid (Aspirin) in treating postoperative pain].

In a randomized, double-center, double-blind, parallel group study the analgesic effect of a single dose of paracetamol (1000 mg) and acetyl salicylic acid (1000 mg) was compared with placebo in patients with moderate to severe postoperative pain following the surgical removal of a wisdom tooth. The most important finding was the statistically significantly shorter period until the onset of the action of paracetamol as against acetyl salicylic acid.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Relief of severe pain with acetaminophen in a new dose formulation versus propoxyphene hydrochloride 65 mg. and placebo: a comparative double-blind study.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

An appraisal of codeine as an analgesic: single-dose analysis.

Codeine, a relatively weak oral narcotic agent, is the most frequently prescribed oral opiate drug. It is also frequently utilized as a control drug in comparative analgesic efficacy studies. These studies are often single dose analysis of pain relief following surgery or childbirth. We conducted a single dose, post-operative analysis of 116 patients who were randomly assigned to receive codeine 60 mg, acetaminophen 600 mg, the combination of codeine and acetaminophen at these doses, or a placebo. Only the combination agent was uniformly superior to placebo. Codeine 60 mg was not consistently superior to placebo in this post-operative single dose analysis. A review of the literature confirms the difficulty in unequivocally establishing the value of codeine as an analgesic, in acceptable oral doses, in the single dose setting. Previous reports, however, suggest that the multiple doses of codeine may afford adequate analgesia. Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Butorphanol/acetaminophen double-blind study in postoperative pain.

An oral butorphanol/acetaminophen (4 mg/650 mg) combination product was evaluated for analgesic activity in 120 postoperative patients employing a double-blind experimental design. The combination product was significantly (p less than 0.05) superior to either butorphanol (4 mg) or acetaminophen (650 mg) as well as placebo. Except for acetaminophen which was only significantly different (p less than 0.05) from placebo at 2 hours according to pain relief, all other treatments were superior to placebo over the entire 4 hour observation period. The data demonstrate that butorphanol and acetaminophen have at least additive analgesic activity with a suggestion of synergism. A single tablet dose of the combination product (butorphanol 2 mg/acetaminophen 325 mg) was evaluated in a second study involving 60 patients and was significantly (p less than 0.05) superior to placebo. Both studies demonstrate that the butorphanol/acetaminophen combination product has potent analgesic activity with a minimal side effect profile.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Augmentation of acetaminophen analgesia by the antihistamine phenyltoloxamine.

A double-blind, placebo-controlled, parallel-group study was performed to compare the analgesic activity of the combination of 650 mg acetaminophen plus 60 mg phenyltoloxamine citrate with that of 650 mg acetaminophen alone. Two hundred female inpatients who had severe pain associated with a recent episiotomy procedure were randomly assigned to receive a single dose of one of the two active treatments or a placebo. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard subjective scales for pain intensity and relief, a number of derived variables based on these data and two global measures. For essentially all measures, the two active treatments were significantly superior to the placebo control. The combination was significantly superior to acetaminophen alone for all analgesic measures including SPID, TOTAL, and global ratings. The results of this study demonstrate that 60 mg phenyltoloxamine produces significant augmentation of the analgesic activity of 650 mg acetaminophen in postepisiotomy pain.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

An investigation into the comparative efficacy of soluble aspirin and solid paracetamol in postoperative pain after third molar surgery.

To compare the efficacy of soluble aspirin 900 mg and paracetamol 1,000 mg in patients with postoperative pain after third molar surgery. A randomised, placebo controlled, double-blind study. Day stay units of Oral and Maxillofacial Surgery at Cardiff Dental Hospital and Hexham General Hospital, Northumberland. One hundred and sixty-seven (104 female) patients who required the removal of their impacted third molars under general anaesthesia. In the early postoperative period, patients were medicated with either a single dose of soluble aspirin 900 mg, solid paracetamol 1,000 mg or placebo. Pain intensity was measured on 100 mm visual analogue scales at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120 and 240 minutes after dosing. Other efficacy variables evaluated included time to rescue medication and an overall assessment of the study medication efficacy by the patient on completion of the study. One hundred and sixty-seven patients consented to take part in the study, but only 153 were medicated. Of the 14 patients not treated, 10 failed to develop sufficient pain to enter the study, two withdrew consent, one had an adverse reaction to the general anaesthetic and one was a protocol violator. Over the four hour investigation period, patients treated with soluble aspirin reported significantly less pain when compared with those treated with paracetamol (mean difference in AUC(0-240) = -2001, 95% CI -3893 to -109, p=0.038) and placebo (mean difference in AUC(0-240) = -3470, 95% CI -5719 to -1221, p=0.003). Similarly, at 20 and 30 minutes after dosing, patients in the soluble aspirin group were reporting significantly less pain than those in the paracetamol treatment group (mean difference in pain intensity: at 20 minutes -7.9, 95% CI -15.3 to -0.6, p=0.035; at 30 minutes -10.6, 95% CI -18.6 to -2.6, p=0.010). There were no significant differences between treatment groups with respect to the number of patients requiring rescue medication, however the time to dosing was significantly longer for those taking soluble aspirin when compared with placebo (hazard ratio 2.34, 95% CI 1.41 to 3.88, p<0.001). The findings from this study showed that soluble aspirin 900 mg provides significant and more rapid analgesia than paracetamol 1,000 mg in the early postoperative period after third molar surgery.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Analgesic efficacy of low-dose diclofenac versus paracetamol and placebo in postoperative dental pain.

To compare the efficacy and safety of diclofenac-K (12.5 mg) vs paracetamol (500 mg) and placebo given in a flexible dosage regimen to treat pain resulting from extraction of impacted third molar teeth. This was a 2-day, double-blind, double-dummy, randomized, parallel-group, placebo-controlled study of diclofenac-K (12.5 mg) tablets vs paracetamol (500 mg) tablets and placebo in patients with moderate or severe pain within 8 hours of extraction of impacted third molars. After the first 2-tablet dose, patients took on average 2.5 additional tablets of diclofenac-K or 2.4 tablets of paracetamol, almost all as 1-tablet doses. Most placebo patients discontinued by taking rescue medication (ibuprofen 200 mg) on the first day. Pain relief after the initial dose of diclofenac-K (2 x 12.5 mg) was superior to placebo (P < .01 for all efficacy outcomes) and comparable to paracetamol (2 x 500 mg). About 30% of patients in each active treatment group took rescue medication during the study, compared to 78% on placebo. About 70% in each active treatment group considered the overall pain relief to be "some," "a lot," or "complete" compared to only 15% on placebo. The incidence of adverse events in each active treatment group was low and comparable between the treatments. An initial double-dose of diclofenac-K (2 x 12.5 mg) or paracetamol (2 x 500 mg) adequately relieved the most intense postoperative pain, and the flexible multiple dose regimen (1 or 2 tablets) maintained adequate pain relief thereafter. Most patients needed only 1-tablet doses following the initial 2-tablet dose.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

A double-blind randomized study of an aspirin/caffeine combination versus acetaminophen/aspirin combination versus acetaminophen versus placebo in patients with moderate to severe post-partum pain.

In a double-blind, randomized controlled trial among 500 post-partum patients experiencing moderate to severe pain, a single oral dose of an aspirin/caffeine combination (800 mg aspirin, 65 mg caffeine) provided significantly more pain relief at 2 hours than did a higher dose of an acetaminophen/aspirin combination (648 mg acetaminophen, 648 mg aspirin) and a higher dose of acetaminophen alone (1000 mg acetaminophen). At 3 and 4 hours, the acetaminophen/aspirin combination as well as the aspirin/caffeine combination were significantly superior to acetaminophen alone. At all times, all three drugs were significantly superior to placebo. There were no clinically significant adverse reactions. These results provide evidence of a potentiating effect of caffeine on aspirin's analgesic potency.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Evaluation of flurbiprofen, acetaminophen, an acetaminophen-codeine combination, and placebo in postoperative oral surgery pain.

Eighty-eight 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 flurbiprofen 100 mg, acetaminophen 600 mg, a combination of acetaminophen 600 mg with codeine 60 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medicating. Estimates of sum of pain intensity differences, peak pain intensity differences, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy. Based on the 12-hour data, acetaminophen alone did not differ significantly from placebo; however, it was superior to placebo for measures of total effect based on the 4-hour data. Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication. All medications had manifested an effect by hour 1; analgesia persisted for 12 hours for flurbiprofen, 6 hours for acetaminophen-codeine, and 3 hours for acetaminophen alone. The frequency of adverse effects was similar for the active medications.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Comparative study of flurbiprofen, zomepirac sodium, acetaminophen plus codeine, and acetaminophen for the relief of postsurgical dental pain.

The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen (Ansaid, Upjohn) were compared with 100 mg of zomepirac sodium, 650 mg of acetaminophen plus 60 mg of codeine, 650 mg of acetaminophen alone, and placebo in a randomized, double-blind, parallel-group study. A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours. For many efficacy variables, all active treatments were significantly (p less than or equal to 0.05) more effective than placebo. The two doses of flurbiprofen gave approximately similar results, suggesting a plateau effect above 50 mg. With the exception of relief at one hour, there were no significant differences between zomepirac and either dose of flurbiprofen. However, the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours. The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine. At the first hour, acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen. After the first hour, flurbiprofen resulted in greater mean scores than acetaminophen alone or acetaminophen plus codeine, and these differences were significant at the fifth and sixth hours. Five patients had adverse reactions while receiving acetaminophen, acetaminophen plus codeine, or placebo. There were no adverse effects with flurbiprofen or zomepirac.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

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.

CD004602

A single dose of paracetamol provides effective analgesia for about half of patients with acute postoperative pain, for a period of about four hours, and is associated with few, mainly mild, adverse events.

Diflunisal. A new oral analgesic with an unusually long duration of action.

The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal (Dolobid), a new nonsteroidal anti-inflammatory analgesic, was compared in a double-blind study with that of acetaminophen, 600 mg, the combination of acetaminophen, 600 mg, with codeine phosphate, 60 mg, and placebo in 159 oral surgery outpatients. Using a self-rating record, patients rated their pain and its relief hourly for 12 hours after medication. Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination. Diflunisal proved to have an unusually long duration of analgesic action. Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5, respectively; both doses of diflunisal were significantly superior through the end of the 12-hour observation period. None of the active treatments produced more side effects than the placebo.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma.

The aim of this study was to compare the efficacy and safety of once-daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma. Eligible patients requiring budesonide or equivalent 320-640 microg (ex-mouthpiece, equivalent to 400-800 microg; Turbohalertrade mark) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280 microg/day; ex-mouthpiece, equivalent to 1600 microg/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of 7% or 0.15 L were randomised to ciclesonide 320 microg (ex-actuator, equivalent to 400 microg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 microg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint. In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P=0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P=0.017). Rescue medication use decreased significantly only for ciclesonide patients (P=0.009). Frequency of adverse events was low in both groups. Ciclesonide 320 microg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 microg once daily in persistent asthma.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

A multinational, 12-week, randomized study comparing the efficacy and tolerability of ciclesonide and budesonide in patients with asthma.

Ciclesonide is a new lung-activated inhaled corticosteroid (ICS) that has shown efficacy in previous placebo-controlled and comparative studies in patients with persistent asthma. It is important to compare new treatments with existing ICSs to obtain relative data concerning their efficacy and tolerability. This study compared the efficacy and tolerability of ciclesonide QD with budesonide BID in patients with asthma. This 12-week, randomized study was conducted at 62 study sites across Europe. Male and female patients aged 12 to 75 years with primarily mild to moderate asthma were enrolled. This study was double blind with respect to the ciclesonide dose and open label for budesonide, as placebofor budesonide was not available. Patients were randomly assigned to receive inhaled ciclesonide 80 or 320 microg QD (morning) or budesonide 200 microg BID for 12 weeks. Efficacy and tolerability assessments were performed at weeks 0 (baseline), 4, 8, and 12. The primary end point was the change from baseline in forced expiratory volume in 1 second (FEV1) at 12 weeks. Secondary end points were changes from baseline in morning peak expiratory flow (PEF), asthma symptom scores, and rescue medication use. Tolerability was assessed throughout the study by monitoring of standard laboratory variables (hematology and biochemistry); physical examination, including vital signs; reporting of adverse events (AEs); and 24-hour urinary cortisol as a measure of hypothalamic-pituitary-adrenal-axis function. Five hundred fifty-four patients were randomized (301 men, 253 women; mean age, 41.3 years; ciclesonide 80 microg QD, 182 patients; ciclesonide 320 microg QD, 195; budesonide 200 microg BID, 177). Demographic and baseline clinical characteristics, including age, sex, weight, and (FEV1) were similar between the 3 groups. Compared with baseline values, week-12 FEV1 (least squares mean [LSM] [SEM] A, +0.267 [0.035], +0.256 [0.033], and +0.355 [0.034] L, respectively; all, P<0.001) and morning PEF (LSM [SEM] Delta, +12 [5], +17 [4], and +21 [4] L/min, respectively; all, P<or=0.008) were significantly improved with ciclesonide 80 and 320 microg QD and budesonide 200 microg BID. At 12 weeks, ciclesonide was found to be noninferior to budesonide with regard to mean changes from baseline in (FEV1) (intent to treat [ITT]: 97.5% CI for ciclesonide 80 microg QD vs budesonide 200 microg BID, -0.192 to 0.015; 97.5 CI for ciclesonide 320 microg QD vs budesonide 200 microg BID, -0.200 to 0.001) and morning PEF (ITT. 97.5% CI for ciclesonide 80 microg QD vs budesonide 200 microg BID, -22 to 5; 97.5% CI for ciclesonide 320 microg QD vs budesonide 200 microg BID, -17 to 10). Similar findings were seen in the per-protocol population. Week-12 daily, daytime, and nighttime asthma symptom scores and rescue medication use were significantly decreased from baseline in all 3 treatment groups (all, P<0.001). The prevalences of AEs were similar across all 3 treatment groups. Week-12 mean urinary cortisol excretion was statistically similar to baseline with both ciclesonide doses (Delta, -0.54 and +0.16 nmol/mmol creatinine with ciclesonide 80 and 320 microg QD, respectively) but was significantly reduced from baseline with budesonide (Delta, -1.42 nmol/mmol creatinine; P<0.05). The results of this study in patients with primarily mild to moderate asthma suggest that ciclesonide 80 and 320 microg QD were similar to budesonide 200 microg BID in improving pulmonary function, controlling asthma symptoms, and reducing the need for rescue medication use. Unlike budesonide, ciclesonide was not associated with significant urinary cortisol suppression in these patients.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

A comparative study of inhaled ciclesonide 160 microg/day and fluticasone propionate 176 microg/day in children with asthma.

Ciclesonide (CIC) is an inhaled corticosteroid (ICS) with high anti-inflammatory activity and low incidence of local and systemic adverse effects. The objective of this study was to compare the efficacy and safety of CIC with fluticasone propionate (FP) in children and adolescents with persistent asthma. This was a 12-week, randomized, double blind, parallel-group study. After a 2-to 4-week baseline period, a total of 556 children (ages 6-15 years) with asthma (forced expiratory volume in 1 sec [FEV(1)], 50% to 90% predicted) were treated twice daily with CIC 80 microg (ex-actuator, equivalent to 100 microg ex-valve) or FP 88 microg (ex-actuator, equivalent to 100 microg ex-valve) administered via a hydrofluoroalkane-propelled metered-dose inhaler. A statistically significant increase from baseline was observed in FEV(1) for both CIC (285 +/- 16 ml) and FP (285 +/- 15 ml) (P < 0.0001 for both) and in morning and evening peak expiratory flow (P < 0.0001 for both). Significant improvements were seen in asthma symptoms, use of rescue medication, and asthma symptom-free days in both treatment groups, without any differences between the treatment groups in changes from baseline. Two FP-treated patients experienced oral candidiasis and one patient experienced voice alteration. Creatinine-adjusted 24-hr urine cortisol levels increased from baseline levels by 10% in the CIC group (P < 0.05) and by 6% in the FP group (not significant). The efficacy and safety of CIC 160 microg/day were comparable to those of FP 176 microg/day in children with asthma. (c) 2006 Wiley-Liss, Inc.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Comparison of twice-daily inhaled ciclesonide and fluticasone propionate in patients with moderate-to-severe persistent asthma.

To investigate the relative efficacy of ciclesonide and fluticasone propionate (FP) administered at comparable microgram doses in maintaining asthma control in patients with moderate-to-severe persistent asthma. This randomized, open-label, parallel-group study enrolled patients aged 12-75 years with a 6-month history of bronchial asthma. To enter a 2-week run-in period, patients had to have received FP 500-1000 microg/day or equivalent at a stable dose for 4 weeks and have a forced expiratory volume in 1s (FEV 1) 80% of predicted. To enter the treatment period, patients had to have the following during run-in: FEV 1 80% of predicted; reversibility of Delta FEV 1 12% after 200-400 microg salbutamol; and 1 day without asthma symptoms during the last 7 days. Patients were randomized to twice-daily ciclesonide 320 microg (ex-actuator) or twice-daily FP 330 microg (ex-actuator) for 6 months. Efficacy was assessed by lung function, asthma exacerbations, asthma symptoms and rescue medication use. Patients completed the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]). Adverse events (AEs), including local oropharyngeal AEs, were recorded. 528 patients were randomized (ciclesonide, n=255; FP, n=273). In both groups, FEV 1 was maintained from baseline to study end (mean increase: ciclesonide 11 mL, FP 24 mL; intention-to-treat [ITT] analysis). The least squares mean+/-standard error of the mean for the treatment difference was -13+/-29 (95% confidence interval [CI]: -70, 44) in the ITT analysis and -27+/-34 (95% CI: -93, 40) in the per-protocol (PP) analysis, demonstrating non-inferiority of ciclesonide to FP. Morning, evening and site-measured PEF improved significantly with both treatments (ITT and PP analyses: p<0.05). Six patients receiving ciclesonide and seven receiving FP (ITT analysis) experienced an asthma exacerbation requiring treatment with oral corticosteroids. Both treatments significantly decreased asthma symptom score sum (ITT and PP analyses: p0.0001) and rescue medication use (ITT and PP analyses: p<0.05), with no significant difference between treatments. Both treatments significantly improved overall AQLQ(S) score (ITT and PP analyses: p<0.05). Significantly more patients experienced candidiasis and dysphonia with FP compared with ciclesonide (p=0.0023). Ciclesonide 320 microg and FP 330 microg administered twice daily over 6 months provided similar efficacy in patients with moderate or severe persistent asthma previously well-controlled by high doses of ICS at baseline. Ciclesonide was associated with fewer local AEs than FP.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Similar efficacy of ciclesonide once daily versus fluticasone propionate twice daily in patients with persistent asthma.

This 12-week, double-blind, parallel-group study compared the efficacy and safety of once daily ciclesonide and twice daily fluticasone propionate in patients aged 12-75 years with persistent asthma. Patients were randomized to once-daily ciclesonide 80 micro g (n = 278) or 160 micro g (n = 271), or twice daily fluticasone propionate 88 micro g (n = 259) (all ex-actuator). Significant improvements from baseline were seen in all three treatment groups for forced expiratory volume in 1 second, asthma symptom scores and rescue medication use (all p < 0.0001). Asthma exacerbation rates were low (each ciclesonide group, n = 2; fluticasone group, n = 1). Adverse event reporting indicated good tolerability. Once daily ciclesonide 80 micro g or 160 micro g showed comparable efficacy and tolerability to twice daily fluticasone propionate 88 micro g in persistent asthma.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma.

Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events. To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma. This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator. For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate. These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Efficacy and safety of once-daily inhaled ciclesonide in adults with mild to moderate asthma: a double-blind, placebo-controlled study.

Inhaled corticosteroids are recommended as first-line therapy for the management of asthma, although side-effects may limit their use. Ciclesonide, a novel pro-drug inhaled corticosteroid, exerts potent and prolonged local anti-inflammatory effects in the lungs, and is considered to have an improved safety and tolerability profile. The aim of this study was to evaluate the efficacy and safety of ciclesonide in adult patients with mild to moderate asthma. A placebo-controlled, multicentre, randomized, double-blind, parallel-group study was conducted. During the 4-week baseline period, patients were given 400 microg/day of beclomethasone dipropionate in a chlorofluorocarbon formulation. After the baseline period, 311 patients were given once-daily 100, 200 or 400 microg of ciclesonide or placebo for an 8-week treatment period without the use of a spacer. The primary efficacy variable was morning PEF. Changes in the morning PEF (least squares mean) at the end of the study were 4.23 L/min (P < 0.001) in the 100 microg group, 3.75 L/min (P < 0.001) in the 200 microg group, -0.40 L/min (P < 0.001) in the 400 microg group, as compared with -24.95 L/min in the placebo group. In the ciclesonide groups, the PEF remained at the same level as the baseline period. No large differences were observed between the placebo group and the ciclesonide groups regarding safety. Once-daily administration of ciclesonide at doses of 100, 200 or 400 microg was shown to be effective in adult patients with mild to moderate asthma. Ciclesonide is considered to have favourable safety profiles and be well tolerated.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Effect of ciclesonide and fluticasone on exhaled nitric oxide in patients with mild allergic asthma.

Ciclesonide is a novel, lung-activated, inhaled corticosteroid with once-daily efficacy and potent anti-inflammatory activity. The aim of the study was to compare the effect of ciclesonide and fluticasone propionate on exhaled nitric oxide (FENO), pulmonary function, and other parameters used in clinical evaluation of patients with mild allergic asthma. The study indicates that ciclesonide (in a daily dose of either 80 or 160 microg) induces both a faster and stronger decrease of FENO in comparison with fluticasone (100 microg twice daily). In both groups of patients treated with ciclesonide, the highest decrease in FENO levels was observed after 2 weeks of treatment. In the group of patients treated with fluticasone, this maximum effect was not observed till 8 weeks. An improvement in spirometric indices was observed in all groups studied. Statistical differences between the groups were not found; however, there was a trend toward higher increase in the group receiving 160 microg of ciclesonide. In all groups studied we observed clinical improvement (asthmatic symptoms and consumption of rescue medication were reduced), but there were no significant differences between these groups. Our results indicate that ciclesonide, compared with fluticasone, has stronger anti-inflammatory activity in patients with mild allergic asthma.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Comparable efficacy of ciclesonide once daily versus fluticasone propionate twice daily in asthma.

Inhaled corticosteroids are the mainstay of therapy in asthma, but local and systemic side effects and adherence remain a concern. Ciclesonide is an inhaled corticosteroid with on-site lung activation that provides potent anti-inflammatory activity and has been shown to have a good safety profile, even at high doses. The aim of this study was to compare the efficacy and safety of once-daily ciclesonide versus twice-daily fluticasone propionate at comparable daily doses in patients with asthma. In this multicenter, randomized, double-blind, double-dummy, parallel group study, 529 patients were randomized to ciclesonide 160 microg once daily or fluticasone propionate 88 microg twice daily for 12 weeks. The primary endpoint was change in lung function. Both ciclesonide and fluticasone propionate significantly improved forced expiratory volume in 1s, forced vital capacity, and morning peak expiratory flow compared with baseline (p<0.0001 for all variables). Both medications reduced asthma symptoms and rescue medication use within the first 24 h. At the tested dose, both medications were equally safe and well tolerated. Ciclesonide 160 microg once daily was as effective as fluticasone propionate 88 microg twice daily in improving lung function and asthma symptoms, and in reducing rescue medication use in patients with asthma.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Comparison of the efficacy of ciclesonide 160 microg QD and budesonide 200 microg BID in adults with persistent asthma: a phase III, randomized, double-dummy, open-label study.

The efficacy of ciclesonide 160 mug QD (given either in the morning or evening) was compared with budesonide 200 mug BID in adults with stable asthma that was pretreated with inhaled corticosteroids. This was a randomized, 3-arm, parallel-group study comparing ciclesonide (given in a double-blind, double-dummy regimen) with open-label budesonide. After 2 to 2.5 weeks, during which patients were treated with budesonide 200 microg BID, patients (n = 405) were randomly assigned to receive ciclesonide 160 microg QD AM or 160 microg QD pm, or budesonide 200 microg BID (all administered by metered-dose inhaler) for 12 weeks. All patients received 2 puffs of medication (or placebo) in the morning and evening. The primary efficacy variable was the difference in spirometric forced expiratory volume in 1 second (FEV(1) in liters) from randomization to study end. Secondary efficacy end points were forced vital capacity, peak expiratory flow by spirometry, and diary assessments of peak expiratory flow, asthma symptoms, and rescue medication use. Adverse events were assessed by patient report, investigator observation, physical examination, and laboratory testing; events were classified as mild, moderate, or severe. Baseline demographic characteristics with regard to sex, age, weight, smoking status, baseline medication use, and FEV(1) were balanced among the treatment groups. Over the course of treatment, both ciclesonide and budesonide maintained FEV(1) compared with baseline. Both ciclesonide regimens were as effective as budesonide 200 microg BID in maintaining FEV(1) during the treatment period versus baseline (ciclesonide 160 microg QD am: 95% CI, -0.120 to 0.045 vs budesonide; P = NS; ciclesonide 160 microg QD pm: 95% CI, -0.061 to 0.105 vs budesonide; P = NS). Ciclesonide 160 microg QD (morning or evening) was comparable with budesonide 200 microg BID for maintaining pulmonary function, asthma symptom scores, and rescue medication use. The incidence of adverse events was not significantly different among the treatment groups, and most adverse events were not related to study medication. In this study, ciclesonide 160 microg QDwas as effective as budesonide 200 microg BID (400 microg total daily dose) in these adults with persistent asthma. Both treatments were well tolerated.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Comparison of the efficacy and safety of ciclesonide 160 microg once daily vs. budesonide 400 microg once daily in children with asthma.

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Randomized comparison of the efficacy and safety of ciclesonide and budesonide in adolescents with severe asthma.

The aim of the study was to investigate the efficacy and safety of ciclesonide compared with budesonide in adolescents with severe asthma. In this randomized, double-blind, double-dummy, parallel-group study, patients aged 12-17 years with severe asthma were treated with budesonide 400 microg once daily (QD) in a 2-week run-in period. At randomization, eligible patients were assigned 2:1 to ciclesonide 320 microg QD (ex-actuator) or budesonide 800 microg QD (metered dose), respectively, in the evening. Forced expiratory volume in 1s (FEV(1)) was the primary variable. Patients recorded asthma symptom score and rescue medication use in diaries. Safety assessments included adverse events (AEs) and 24-h urine cortisol. Four hundred and three patients were randomized. Ciclesonide 320 microg QD and budesonide 800 microg QD significantly increased FEV(1) (least-squares mean: 505 and 536 mL, respectively; both p<0.0001 versus baseline) in the intention-to-treat (ITT) population. Lower limits of the 95% confidence intervals (ITT: -138 mL; per-protocol: -122 mL) were above the non-inferiority limit (-150 mL). Median percentage of days without asthma symptoms and without rescue medication use was 84% with ciclesonide and 85% with budesonide. AEs were unremarkable, with no cases of confirmed candidiasis. Median creatinine-adjusted urine cortisol significantly decreased with budesonide treatment (15.9-13.7 nmol cortisol/mmol creatinine; p=0.0086 versus baseline), but not with ciclesonide (p=0.1125). Ciclesonide 320 microg QD showed similar efficacy to budesonide 800 microg QD in adolescents with severe asthma. Ciclesonide was well tolerated and, unlike budesonide, had no effect on urine cortisol levels. EudraCT No.: 2004-001233-41.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Airway and systemic effects of hydrofluoroalkane formulations of high-dose ciclesonide and fluticasone in moderate persistent asthma.

There are no data comparing the relative effects of high-dose ciclesonide (CIC) and fluticasone propionate (FP) on airway and systemic outcomes in patients with moderate persistent asthma. We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor (hCRF) and bronchial hyperresponsiveness to methacholine as the primary outcome variables, in addition to secondary outcomes of overnight 10-h urinary cortisol (OUC) levels, exhaled nitric oxide levels, lung function, symptoms, and quality of life. Fourteen patients with moderate persistent asthma (mean FEV(1), 67% predicted [prior to each randomized treatment]) completed the study, which had a randomized, double-blind, double-dummy, crossover design, per protocol. Patients stopped receiving their usual inhaled corticosteroids for the duration of the study and instead began receiving salmeterol, 50 mug twice daily, and montelukast, 10 mg once daily, for the 2-week washout periods prior to each randomized treatment, in order to prevent dropouts after withdrawal from inhaled corticosteroid therapy. Patients received 4 weeks of either CIC, 200 microg ex-valve (160 microg ex-actuator) four puffs twice daily, plus FP-placebo, four puffs twice daily, or FP, 250 microg ex-valve (220 microg ex-actuator) four puffs twice daily, plus CIC-placebo, four puffs twice daily. Salmeterol and montelukast were withheld for 72 h prior to each postwashout baseline visit, and CIC or FP was withheld for 12 h prior to each posttreatment visit. FP, but not CIC, when compared to respective baseline values, significantly suppressed (p < 0.05) plasma cortisol levels as follows: FP prior to receiving hCRF: geometric mean fold difference, 1.2; 95% confidence interval (CI), 1.1 to 1.3; CIC prior to receiving hCRF: geometric mean fold difference, 0.9; 95% CI, 0.8 to 1.0; FP 30 min after receiving hCRF: geometric mean fold difference, 1.2; 95% CI, 1.1 to 1.3; CIC 30 min after receiving hCRF: geometric mean fold difference, 1.0; 95% CI, 0.9 to 1.2; OUC after FP administration: geometric mean fold difference, 1.9; 95% CI, 1.4 to 2.6; OUC after CIC administration: geometric mean fold difference, 1.2; 95% CI, 0.9 to 1.5. There was also a significantly lower (p < 0.05) mean value for OUC levels after FP administration than after CIC administration (geometric mean fold difference, 1.5; 95% CI, 1.1 to 2.0). Therapy with CIC and FP, compared to respective baselines, significantly increased (p < 0.05) the provocative concentration of methacholine causing a 20% fall in FEV(1), as follows: CIC: doubling dilution difference, 0.8; 95% CI, 0.1 to 1.6; FP: doubling dilution difference, 1.0; 95% CI, 0.1 to 2.0. It also significantly reduced (p < 0.05) exhaled nitric oxide levels, as follows: CIC: geometric mean fold difference, 1.2; 95% CI, 1.1 to 1.3; FP: geometric mean fold difference, 1.9; 95% CI, 1.3 to 2.8. There was no effect on other secondary efficacy outcomes. FP, 2,000 microg daily, but not CIC, 1,600 microg daily, significantly suppressed hypothalamic-pituitary-adrenal axis outcomes, with OUC levels being lower after FP administration than after CIC administration. Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyperresponsiveness and exhaled nitric oxide levels. The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Effects of hydrofluoroalkane formulations of ciclesonide 400 microg once daily vs fluticasone 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma.

There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-moderate persistent asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life. Nineteen mild-to-moderate asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 microg one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 microg two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 microg two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits. There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline. There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma. Longer-term studies are indicated to evaluate their relative efficacy on asthma exacerbations.

CD007031

The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Ciclesonide is more effective than budesonide in the treatment of persistent asthma.

Ciclesonide is a lung-activated inhaled corticosteroid that provides effective control of persistent asthma. The objective of this study was to compare the efficacy and safety of once-daily ciclesonide versus once-daily budesonide in patients with asthma. A total of 399 patients with asthma were randomised to receive once-daily ciclesonide 320 microg ex-actuator (equivalent to 400 microg ex-valve) or once-daily budesonide 400 microg for 12 weeks. The primary endpoint was forced expiratory volume in 1s (FEV(1)). Additional efficacy variables included forced vital capacity (FVC), peak expiratory flow (PEF), asthma symptoms, use of rescue medication and time to onset of effect. Adverse events were monitored throughout the study. Both ciclesonide and budesonide significantly increased FEV(1) from baseline (416 and 321 ml, respectively; p<0.0001). The increase in FEV(1) was significantly greater in ciclesonide-treated patients (95% confidence interval: 0.016-0.174; p=0.019 versus budesonide). Similarly, ciclesonide and budesonide significantly improved FVC and PEF from baseline (p<0.0001), and significantly greater increases occurred with ciclesonide (p=0.034 and 0.019 versus budesonide, respectively). Analysis of morning PEF revealed an earlier onset of action for ciclesonide versus budesonide; a significant improvement was seen by day 2 (p=0.039 versus baseline) with ciclesonide compared with day 7 for budesonide (p=0.047 versus baseline). Adverse events occurred with a similar incidence in both treatment groups. Neither treatment caused significant changes in urinary cortisol levels. Once-daily ciclesonide was more effective than once-daily budesonide in improving FEV(1), FVC and PEF. Ciclesonide also had an earlier onset of action than budesonide in patients with persistent asthma. Both ciclesonide and budesonide had good safety and tolerability profiles.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

Randomised controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care.

To determine whether, in the treatment of major depression in primary care, a brief psychological treatment (problem solving) was (a) as effective as antidepressant drugs and more effective than placebo; (b) feasible in practice; and (c) acceptable to patients. Randomised controlled trial of problem solving treatment, amitriptyline plus standard clinical management, and drug placebo plus standard clinical management. Each treatment was delivered in six sessions over 12 weeks. Primary care in Oxfordshire. 91 patients in primary care who had major depression. Observer and self reported measures of severity of depression, self reported measure of social outcome, and observer measure of psychological symptoms at six and 12 weeks; self reported measure of patient satisfaction at 12 weeks. Numbers of patients recovered at six and 12 weeks. At six and 12 weeks the difference in score on the Hamilton rating scale for depression between problem solving and placebo treatments was significant (5.3 (95% confidence interval 1.6 to 9.0) and 4.7 (0.4 to 9.0) respectively), but the difference between problem solving and amitriptyline was not significant (1.8 (-1.8 to 5.5) and 0.9 (-3.3 to 5.2) respectively). At 12 weeks 60% (18/30) of patients given problem solving treatment had recovered on the Hamilton scale compared with 52% (16/31) given amitriptyline and 27% (8/30) given placebo. Patients were satisfied with problem solving treatment; all patients who completed treatment (28/30) rated the treatment as helpful or very helpful. The six sessions of problem solving treatment totalled a mean therapy time of 3 1/2 hours. As a treatment for major depression in primary care, problem solving treatment is effective, feasible, and acceptable to patients.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

Efficacy of venlafaxine in depressive illness in general practice.

A double-blind, placebo-controlled study of 229 patients with a Research Diagnostic Criteria diagnosis of major, minor or intermittent depression was used to compare the clinical profiles of venlafaxine and imipramine in general practice. Venlafaxine produced a significant improvement compared to placebo in symptoms of depression and anxiety as rated by the total MADRS and percentage of responders, the CGI improvement, the CGI severity of illness, the BSA psychic anxiety item and the HSCL. On a number of these measures, venlafaxine was also significantly more effective than imipramine. Venlafaxine was significantly superior to both imipramine and placebo for the SARS total score and the items 'social/leisure' and 'extended family.' A similar proportion of patients discontinued treatment in each group, but fewer patients on venlafaxine discontinued treatment because of an unsatisfactory response.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

Escitalopram (10-20 mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care.

Escitalopram was compared to placebo in moderately to severely depressed patients in primary care with citalopram as the active reference. Patients were randomized to receive flexible doses of 10-20 mg/day escitalopram (n=155), 20-40 mg/day citalopram (n=160), or placebo (n=154) over an 8-week double-blind period. The primary efficacy parameter was the change from baseline to last assessment in the Montgomery-Asberg Depression Rating Scale total score. Escitalopram produced a statistically significant therapeutic difference of 2.9 points (P=0.002) compared to placebo, and escitalopram was consistently and statistically significantly more efficacious than placebo from week 1 onwards. Analysis of Clinical Global Impression-Severity and Clinical Global Impression-Improvement confirmed the primary efficacy results. By week 8, significantly more patients had responded to treatment with escitalopram than with citalopram (P=0.021) or placebo (P=0.009). Escitalopram was as well tolerated as citalopram and had a similar adverse event profile. Both escitalopram- and citalopram-treated patients had placebo-level adverse event withdrawal rates (3% and 4%, respectively). This study demonstrates the consistent antidepressant efficacy and excellent tolerability of escitalopram 10-20 mg/day in primary care patients with major depressive disorder.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

Controlled trial of amitriptyline in general practice.

A controlled double-blind trial of amitriptyline at two dosage levels (75 and 150 mg/day), amylobarbitone (150 mg/day), and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness. Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups. Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety. Troublesome side effects were equally distributed among the four treatments.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

Effects of antidepressant treatment on the quality of daily life: an experience sampling study.

Although some depression trials have included quality of life (QoL) as an outcome measure, assessments were retrospective and relatively infrequent. Because QoL varies in relation to everyday experience, intensive time-sampling approaches may be useful. The experience sampling method (ESM) was used to assess effects of antidepressant treatment on the quality of life, as measured from moment to moment in daily life (mQoL), and related aspects of daily experience. Primary care patients with a DSM-III-R/DSM-IV diagnosis of major depressive disorder were randomly assigned to imipramine (N = 32) or placebo (N = 31) treatment for 6 weeks, with possible prolongation to 18 weeks. A healthy control group (N = 22) provided normative data. Treatment-related increases in frequency and severity of physical complaints, including those not reported to the general practitioner as side effects, were associated with lowered mQoL; this negative association was especially strong in treatment dropouts. Despite greater clinical improvement at week 6, imipramine patients did not report greater increases than placebo patients in mean mQoL ratings. However, imipramine treatment stabilized mQoL fluctuations and led to reductions in time spent "doing nothing." Patients' decisions to prolong treatment depended on clinical improvement, mQoL changes, and specific early side effects. At 18 weeks, remitted patients still showed deficits on ESM daily life measures relative to healthy controls, even though QoL had returned to normal on retrospective measures. ESM provides new insights in the effects of antidepressant treatment on daily life experiences and should therefore be considered as a supplement to conventional instruments in clinical trials.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

A double-blind, placebo-controlled comparison of sertraline and dothiepin in the treatment of major depression in general practice.

In a double-blind multi-centre study of general practice patients with DSM-III-R major depressive disorder, sertraline (50 or 100 mg/day) was compared with dothiepin (75 or 150 mg/day) and with placebo. There were 83, 96 and 90 patients evaluated in the respective treatment groups; treatment lasted 6 weeks. Patients were assessed on the MADRS, CGI, and Leeds Self-rating Scales. Statistically significant differences (p < 0.05) between sertraline and placebo were found on MADRS and CGI but not the Leeds Scales. In the mild subgroup analyses, there were no significant differences between sertraline and placebo. However, clear significant differences (p < 0.05) between sertraline and placebo were present in the severe subgroup. Dothiepin failed to achieve a statistically significant difference from placebo on any analyses. Seventy-six per cent of patients were treated with 50 mg sertraline and 81% of patients received 150 mg dothiepin. Both sertraline and dothiepin were generally well tolerated; the most frequent side effects with sertraline were nausea, dizziness and headache; with dothiepin the most frequent side effects were dry mouth, somnolence and headache.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

Double-blind placebo-controlled trial of amitriptyline among depressed patients in general practice.

Depressed patients in general practice were included in a double-blind placebo-controlled six-week trial of amitriptyline (median dose 125 mg). The patients were relatively mildly ill and satisfied diagnostic criteria for depression and treatment with antidepressants in routine practice. Amitriptyline was found to be considerably superior to placebo after six weeks and significantly so as early as two weeks after the start of treatment. The effects of the antidepressant were on the core symptoms of depression, and were apparent in all but the most mildly ill patients. The findings suggest that tricyclic antidepressants are of considerable therapeutic benefit to depressed patients in general practice.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks.

To assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression. Randomised, double blind, multicentre, parallel group trial for 8 weeks. Trained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony. 263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32. 1 and F33.1. 1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily. Change from baseline score on the 17 item version of the Hamilton depression scale, the Hamilton anxiety scale, the clinical global impressions scale, Zung's self rating depression scale, and SF-36, and adverse events profile. Hypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean -15.4 (SD 8.1), -12.1 (7.4), and -14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively). At an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

A placebo-controlled multicenter trial of Limbitrol versus its components (amitriptyline and chlordiazepoxide) in the symptomatic treatment of depressive illness.

In a multicenter, placebo-controlled, clinical trial, the efficacy of Limbitrol was compared with that of its components, amitriptyline and chlordiazepoxide. All patients had a diagnosis of primary depression. Data from 279 patients were evaluated using the Hamilton depression scale, the Beck depression inventory, and physician and patient global change measures. Statistically significant differences favoring Limbitrol occurred after 1 week of treatment, and a trend in favor of Limbitrol continued throughout the remaining 3 weeks. In most efficacy comparisons, the combination was as good as, or better than, amitriptyline alone. It was superior to chlordiazepoxide alone after 2 and 4 weeks of treatment. Each component produced an independent contribution to the total therapeutic effect: the chlordiazepoxide effect was more prominent in the first 2 weeks and the amitriptyline effect in the latter 2 weeks. A trend favoring amitriptyline over chlordiazepoxide was evident by week 4. The overall incidence of side effects was comparable in both Limbitrol- and amitriptyline-treated groups. Limbitrol-treated patients exhibited more sedation, but significantly fewer Limbitrol patients discontinued treatment prematurely because of side effects.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

The Norwegian naturalistic treatment study of depression in general practice (NORDEP)-I: randomised double blind study.

To evaluate the efficacy of emotional support and counselling combined with placebo or antidepressants with single or dual mechanism of action in the treatment of depression in primary care. Randomised double blind study. Several locations in Norway. 372 patients with depression. Improvement (clinical remission) reported both by the patient (Montgomery Asberg depression rating scale) and the physician (clinical global improvement and impression scales). Intention to treat analyses showed 47% remission in patients randomised to placebo compared with 61% remission in patients randomised to sertraline (odds ratio 0.56, 95% confidence interval 0.33 to 0.96) and 54% in patients randomised to mianserin (0.75, 0.44 to 1.27). Women responded better than men (1.86, 1.17 to 2.96). Subgroup analyses showed that subjects with recurrent depression (n=273) responded more frequently to sertraline than to placebo (0.43, 0.23 to 0.82) than those having their first episode of depression (1.18, 0.39 to 3.61). Statistically significant interactions between type of drug treatment and history of depression were not shown by logistic regression. The combination of active drug and simple psychological treatment (counselling, emotional support, and close follow up over a 24 week period) was more effective than simple psychological treatment alone, in particular for those with recurrent depression. Overall, women may benefit more than men. If confirmed in future studies, the findings should lead to more differentiated treatment guidelines for depression in primary care.

CD007954

Both TCAs and SSRIs are effective for depression treated in primary care.

Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care.

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), was compared to placebo in a study of patients with major depressive disorder (DSM-IV) who had baseline Montgomery-Asberg Depression Rating Scale (MADRS) total scores >or=22 and <or=40. After a 1-week, single-blind placebo period, patients were randomized to receive escitalopram 10 mg/day (n=191) or placebo (n=189) in an 8-week, double-blind period. The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 (last observation carried forward, LOCF) of 2.7 points (SE 0.85; P=0.002). In further by-week efficacy analyses, the effect of escitalopram was consistently larger than that of placebo (P<0.05) beginning at week 1 (Clinical Global Impression-Improvement score), week 2 (MADRS score) or week 3 (Clinical Global Impression-Severity score). Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo. Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients, although it was infrequent and transient. Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1, and was safe and very well tolerated.

CD005187

No effect was shown for specific outcomes: laboratory-proven influenza, pneumonia and death from pneumonia. An effect was shown for the non-specific outcomes of ILI, GP consultations for ILI and all-cause mortality in individuals ≥ 60. These non-specific outcomes are difficult to interpret because ILI includes many pathogens, and winter influenza contributes < 10% to all-cause mortality in individuals ≥ 60. The key interest is preventing laboratory-proven influenza in individuals ≥ 60, pneumonia and deaths from pneumonia, and we cannot draw such conclusions. The identified studies are at high risk of bias. Some HCWs remain unvaccinated because they do not perceive risk, doubt vaccine efficacy and are concerned about side effects. This review did not find information on co-interventions with HCW vaccination: hand washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, anti-virals, and asking HCWs with ILI not to work. We conclude there is no evidence that vaccinating HCWs prevents influenza in elderly residents in LTCFs. High quality RCTs are required to avoid risks of bias in methodology and conduct, and to test these interventions in combination.

Effectiveness of an influenza vaccine programme for care home staff to prevent death, morbidity, and health service use among residents: cluster randomised controlled trial.

To determine whether vaccination of care home staff against influenza indirectly protects residents. Pair matched cluster randomised controlled trial. Large private chain of UK care homes during the winters of 2003-4 and 2004-5. Nursing home staff (n=1703) and residents (n=2604) in 44 care homes (22 intervention homes and 22 matched control homes). Vaccination offered to staff in intervention homes but not in control homes. The primary outcome was all cause mortality of residents. Secondary outcomes were influenza-like illness and health service use in residents. In 2003-4 vaccine coverage in full time staff was 48.2% (407/884) in intervention homes and 5.9% (51/859) in control homes. In 2004-5 uptake rates were 43.2% (365/844) and 3.5% (28/800). National influenza rates were substantially below average in 2004-5. In the 2003-4 period of influenza activity significant decreases were found in mortality of residents in intervention homes compared with control homes (rate difference -5.0 per 100 residents, 95% confidence interval -7.0 to -2.0) and in influenza-like illness (P=0.004), consultations with general practitioners for influenza-like illness (P=0.008), and admissions to hospital with influenza-like illness (P=0.009). No significant differences were found in 2004-5 or during periods of no influenza activity in 2003-4. Vaccinating care home staff against influenza can prevent deaths, health service use, and influenza-like illness in residents during periods of moderate influenza activity. National Research Register N0530147256.

CD005187

No effect was shown for specific outcomes: laboratory-proven influenza, pneumonia and death from pneumonia. An effect was shown for the non-specific outcomes of ILI, GP consultations for ILI and all-cause mortality in individuals ≥ 60. These non-specific outcomes are difficult to interpret because ILI includes many pathogens, and winter influenza contributes < 10% to all-cause mortality in individuals ≥ 60. The key interest is preventing laboratory-proven influenza in individuals ≥ 60, pneumonia and deaths from pneumonia, and we cannot draw such conclusions. The identified studies are at high risk of bias. Some HCWs remain unvaccinated because they do not perceive risk, doubt vaccine efficacy and are concerned about side effects. This review did not find information on co-interventions with HCW vaccination: hand washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, anti-virals, and asking HCWs with ILI not to work. We conclude there is no evidence that vaccinating HCWs prevents influenza in elderly residents in LTCFs. High quality RCTs are required to avoid risks of bias in methodology and conduct, and to test these interventions in combination.

Effect of influenza vaccination of nursing home staff on mortality of residents: a cluster-randomized trial.

To evaluate the effect of staff influenza vaccination on all-cause mortality in nursing home residents. Pair-matched cluster-randomized trial. Forty nursing homes matched for size, staff vaccination coverage during the previous season, and resident disability index. All persons aged 60 and older residing in the nursing homes. Influenza vaccine was administered to volunteer staff after a face-to-face interview. No intervention took place in control nursing homes. The primary endpoint was total mortality rate in residents from 2 weeks before to 2 weeks after the influenza epidemic in the community. Secondary endpoints were rates of hospitalization and influenza-like illness (ILI) in residents and sick leave from work in staff. Staff influenza vaccination rates were 69.9% in the vaccination arm versus 31.8% in the control arm. Primary unadjusted analysis did not show significantly lower mortality in residents in the vaccination arm (odds ratio=0.86, P=.08), although multivariate-adjusted analysis showed 20% lower mortality (P=.02), and a strong correlation was observed between staff vaccination coverage and all-cause mortality in residents (correlation coefficient=-0.42, P=.007). In the vaccination arm, significantly lower resident hospitalization rates were not observed, but ILI in residents was 31% lower (P=.007), and sick leave from work in staff was 42% lower (P=.03). These results support influenza vaccination of staff caring for institutionalized elderly people.

CD005187

No effect was shown for specific outcomes: laboratory-proven influenza, pneumonia and death from pneumonia. An effect was shown for the non-specific outcomes of ILI, GP consultations for ILI and all-cause mortality in individuals ≥ 60. These non-specific outcomes are difficult to interpret because ILI includes many pathogens, and winter influenza contributes < 10% to all-cause mortality in individuals ≥ 60. The key interest is preventing laboratory-proven influenza in individuals ≥ 60, pneumonia and deaths from pneumonia, and we cannot draw such conclusions. The identified studies are at high risk of bias. Some HCWs remain unvaccinated because they do not perceive risk, doubt vaccine efficacy and are concerned about side effects. This review did not find information on co-interventions with HCW vaccination: hand washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, anti-virals, and asking HCWs with ILI not to work. We conclude there is no evidence that vaccinating HCWs prevents influenza in elderly residents in LTCFs. High quality RCTs are required to avoid risks of bias in methodology and conduct, and to test these interventions in combination.

Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients.

Vaccination of health care workers (HCWs) is recommended as a strategy for preventing influenza in elderly patients in long-term care. However, there have been no controlled studies to show whether this approach is effective. During the winter of 1994-1995, 1059 patients in 12 geriatric medical long-term-care sites, randomized for vaccination of HCWs, were studied. In hospitals where HCWs were offered vaccination, 653 (61%) of 1078 were vaccinated. Vaccination of HCWs was associated with reductions in total patient mortality from 17% to 10% (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40-0.80) and in influenza-like illness (OR, 0.57; 95% CI, 0.34-0.94). Vaccination of patients was not associated with significant effects on mortality (OR, 1.15; 95% CI, 0.81-1.64). Results of this study support recommendations for vaccination against influenza of HCWs in long-term geriatric care. Vaccination of frail elderly long-term-care patients may not give clinically worthwhile benefits.

CD005187

No effect was shown for specific outcomes: laboratory-proven influenza, pneumonia and death from pneumonia. An effect was shown for the non-specific outcomes of ILI, GP consultations for ILI and all-cause mortality in individuals ≥ 60. These non-specific outcomes are difficult to interpret because ILI includes many pathogens, and winter influenza contributes < 10% to all-cause mortality in individuals ≥ 60. The key interest is preventing laboratory-proven influenza in individuals ≥ 60, pneumonia and deaths from pneumonia, and we cannot draw such conclusions. The identified studies are at high risk of bias. Some HCWs remain unvaccinated because they do not perceive risk, doubt vaccine efficacy and are concerned about side effects. This review did not find information on co-interventions with HCW vaccination: hand washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, anti-virals, and asking HCWs with ILI not to work. We conclude there is no evidence that vaccinating HCWs prevents influenza in elderly residents in LTCFs. High quality RCTs are required to avoid risks of bias in methodology and conduct, and to test these interventions in combination.

Effects of influenza vaccination of health-care workers on mortality of elderly people in long-term care: a randomised controlled trial.

Vaccination of health-care workers has been claimed to prevent nosocomial influenza infection of elderly patients in long-term care. Data are, however, limited on this strategy. We aimed to find out whether vaccination of health-care workers lowers mortality and the frequency of virologically proven influenza in such patients. In a parallel-group study, health-care workers in 20 long-term elderly-care hospitals (range 44-105 patients) were randomly offered or not offered influenza vaccine (cluster randomisation, stratified for policy for vaccination of patients and hospital size). All deaths among patients were recorded over 6 months in the winter of 1996-97. We selected a random sample of 50% of patients for virological surveillance for influenza, with combined nasal and throat swabs taken every 2 weeks during the epidemic period. Swabs were tested by tissue culture and PCR for influenza viruses A and B. Influenza vaccine uptake in health-care workers was 50.9% in hospitals in which they were routinely offered vaccine, compared with 4.9% in those in which they were not. The uncorrected rate of mortality in patients was 102 (13.6%) of 749 in vaccine hospitals compared with 154 (22.4%) of 688 in no-vaccine hospitals (odds ratio 0.58 [95% CI 0.40-0.84], p=0.014). The two groups did not differ for proportions of patients positive for influenza infection (5.4% and 6.7%, respectively); at necropsy, PCR was positive in none of 17 patients from vaccine hospitals and six (20%) of 30 from no-vaccine hospitals (p=0.055). Vaccination of health-care workers was associated with a substantial decrease in mortality among patients. However, virological surveillance showed no associated decrease in non-fatal influenza infection in patients.

CD005187

No effect was shown for specific outcomes: laboratory-proven influenza, pneumonia and death from pneumonia. An effect was shown for the non-specific outcomes of ILI, GP consultations for ILI and all-cause mortality in individuals ≥ 60. These non-specific outcomes are difficult to interpret because ILI includes many pathogens, and winter influenza contributes < 10% to all-cause mortality in individuals ≥ 60. The key interest is preventing laboratory-proven influenza in individuals ≥ 60, pneumonia and deaths from pneumonia, and we cannot draw such conclusions. The identified studies are at high risk of bias. Some HCWs remain unvaccinated because they do not perceive risk, doubt vaccine efficacy and are concerned about side effects. This review did not find information on co-interventions with HCW vaccination: hand washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, anti-virals, and asking HCWs with ILI not to work. We conclude there is no evidence that vaccinating HCWs prevents influenza in elderly residents in LTCFs. High quality RCTs are required to avoid risks of bias in methodology and conduct, and to test these interventions in combination.

Influenza vaccination levels and influenza-like illness in long-term-care facilities for elderly people in Niigata, Japan, during an influenza A (H3N2) epidemic.

Surveys on influenza vaccination and illness in long-term-care facilities in Niigata Prefecture during an influenza A (H3N2) epidemic revealed that >20% of facilities had outbreaks and >10% of residents experienced influenza. Outbreaks and number of cases were significantly reduced by vaccination, which should be strongly recommended for institutionalized elderly people.

CD002119

There is no evidence to suggest that spinal manipulation is effective in the treatment of dysmenorrhoea. In the one trial reporting on adverse effects there was no greater risk of such events with spinal compared with sham manipulation.

The effect of spinal manipulation on pain and prostaglandin levels in women with primary dysmenorrhea.

The primary objectives of this study were to compare the effect of spinal manipulation vs. sham manipulation on a) circulating plasma levels of the prostaglandin F2a metabolite, 15-keto-13,14-dihydroprostaglandin (KDPGF2a), b) perceived abdominal and back pain and c) perceived menstrual distress in women with primary dysmenorrhea. This randomized clinical pilot study investigated the outcome measures before and after either a spinal manipulation treatment (SMT) or a sham manipulation. All subjects were treated at the National College Chiropractic clinic, a private chiropractic clinic in the suburban Chicago area. Forty-five women with a history of primary dysmenorrhea were recruited from the local community. The volunteers ranged in age from 20-49 (mean age = 30.3 yr), and were entered into the study between April 1990 and January 1991. Twenty-four were randomly assigned to the spinal manipulation group and 21 were assigned to the sham group. Subjects treated with spinal manipulation were placed in a side-lying position with the bottom leg straight and the top leg flexed at the knee and hip. They received a high-velocity, short lever, low-amplitude thrust to all clinically relevant vertebral levels within T10 and L5-S1 and the sacroiliac joints. In the sham manipulation, subjects were placed in a side-lying position with both hips and knees flexed. Their manipulation consisted of a similar thrust administered to the midline base of the sacrum. Perceived abdominal and back pain were measured with a visual analog scale, and menstrual distress was measured with the Menstrual Distress Questionnaire. Both were administered 15 min before and 60 min after treatment. Blood samples were collected by venipuncture for the determination of plasma levels of KDPGF2a at the same times. The plasma was then assayed for KDPGF2a by radioimmunoassay. Analysis of covariance and paired Student's t tests were used for the statistical evaluation. Immediately after treatment, the perception of pain and the level of menstrual distress were significantly reduced by SMT. This reduction was associated with a significant reduction in plasma levels of KDGPF2a in the SMT group. A significant and similar reduction in plasma KDPGF2a also occurred in the sham group, indicating that a placebo effect was associated with a single sham intervention. This randomized pilot study suggests that SMT may be an effective and safe nonpharmacological alternative for relieving the pain and distress of primary dysmenorrhea. However, the large change in KDPGF2a observed in both treatment groups clearly indicates that further studies with more subjects, studied over a longer time frame, are needed to resolve the question of a placebo effect.

CD002119

There is no evidence to suggest that spinal manipulation is effective in the treatment of dysmenorrhoea. In the one trial reporting on adverse effects there was no greater risk of such events with spinal compared with sham manipulation.

Spinal manipulative therapy versus a low force mimic maneuver for women with primary dysmenorrhea: a randomized, observer-blinded, clinical trial.

Non-drug therapies for women with primary dysmenorrhea are primarily based on anecdotal evidence and small-scale clinical studies. This randomized, observer-blinded, clinical trial evaluated the efficacy of spinal manipulative therapy (SMT) in the treatment of women with primary dysmenorrhea. Women were recruited from the Chicago metropolitan area and evaluated for inclusion through four screening levels. One hundred thirty eight women, ages 18-45, with primary dysmenorrhea diagnosed by participating gynecologists, were randomly assigned to either SMT or a low-force mimic (LFM) maneuver. No treatment occurred at menstrual cycle 1. Treatment for both groups took place on day 1 of cycles 2, 3 and 4, and prophylactic treatment of three visits took place during the 7 days before cycles 3 and 4. Main outcome measures were the Visual Analog Scale (VAS) and plasma concentration of the prostaglandin F2alpha metabolite, 15-keto-13,14-dihydro-prostaglandin F2alpha (KDPGF2alpha), measured 15 min before treatment and 60 min after treatment on day 1 of four consecutive menstrual cycles. The Moos' Menstrual Distress Questionnaire (MDQ) was also administered after treatment on day 1 of each cycle. At cycle 2, the post-treatment VAS scores decreased for both groups, with no statistically significant difference in pre- to post-treatment scores between the two groups (P = 0.44). The changes in pre- to post-treatment KDPGF2alpha levels were not statistically different between the SMT and LFM groups (P = 0.15). No treatment effects were detected over the three cycles for VAS, KDPGF2alpha or MDQ (P = 0.65, P = 0.61 and P = 0.78, respectively). However, there were statistically significant linear time effects for VAS (P = 0.008), MDQ (P < 0.001), and borderline significance for KDPGF2alpha (P = 0.054); these decreases were not considered clinically meaningful. The LFM maneuver used in this study was designed to act as a 'placebo-like' control treatment in comparison with SMT. Although it is possible that the trial did not continue long enough for any placebo effect of the LFM to wash out, it seems more likely that this maneuver was indistinguishable from SMT. Therefore, the postulated superior benefit of high-velocity, short-lever, low-amplitude, high-force spinal manipulation to a low-force maneuver is not supported by the results of this study. 1999 International Association for the Study of Pain.

CD007583

We found evidence, of moderate quality, that radiation decreases the risk of disease progression compared with no further treatment, but little evidence that it might improve overall survival, in stage IB cervical cancer. The evidence on serious adverse events was equivocal.

Radical pelvic surgery versus radical surgery plus radiotherapy for stage Ib carcinoma of the cervix uteri. Preliminary results of a prospective randomized clinical study.

In a preliminary report of a prospective controlled study treatment results and therapy morbidity of 60 patients with stage pT1bNoMo carcinoma of the uterine cervix treated by radical surgery only (Wertheim-Meigs) were compared with those of 60 patients treated by radical surgery followed by a postoperative external radiotherapy. The median duration of follow-up was 44 (24--72) months. Comparing the survival probability analyzed by life-table-method up to 18 months there was a significant better result for patients treated with surgery only. However, after that the study demonstrated comparable therapeutic results with the two therapeutic regimens. There was no difference of tumor size in patients who died after surgery alone and those who died after combined therapy. The therapy morbidity was slightly greater in patients treated by combined therapy. Especially lymphedemas of the leg developed more frequent in patients treated with combined surgery and radiotherapy. Preliminary analysis of the study does not demonstrate any beneficial effect of postoperative radiotherapy followed a radical hysterectomy with pelvic lymphonodectomy in cervical cancer stage pT1bNoMo, but optimal staging, radical surgery and carefully histological examination of the removed tissue are essential needs for this approach.

CD007583

We found evidence, of moderate quality, that radiation decreases the risk of disease progression compared with no further treatment, but little evidence that it might improve overall survival, in stage IB cervical cancer. The evidence on serious adverse events was equivocal.

A phase III randomized trial of postoperative pelvic irradiation in Stage IB cervical carcinoma with poor prognostic features: follow-up of a gynecologic oncology group study.

To investigate, in a phase III randomized trial, whether postoperative external-beam irradiation to the standard pelvic field improves the recurrence-free interval and overall survival (OS) in women with Stage IB cervical cancers with negative lymph nodes and certain poor prognostic features treated by radical hysterectomy and pelvic lymphadenectomy. Eligible patients had Stage IB cervical cancer with negative lymph nodes but with 2 or more of the following features: more than one third (deep) stromal invasion, capillary lymphatic space involvement, and tumor diameter of 4 cm or more. The study group included 277 patients: 137 randomized to pelvic irradiation (RT) and 140 randomized to observation (OBS). The planned pelvic dose was from 46 Gy in 23 fractions to 50.4 Gy in 28 fractions. Of the 67 recurrences, 24 were in the RT arm and 43 were in the OBS arm. The RT arm showed a statistically significant (46%) reduction in risk of recurrence (hazard ratio [HR] = 0.54, 90% confidence interval [CI] = 0.35 to 0.81, p = 0.007) and a statistically significant reduction in risk of progression or death (HR = 0.58, 90% CI = 0.40 to 0.85, p = 0.009). With RT, 8.8% of patients (3 of 34) with adenosquamous or adenocarcinoma tumors recurred vs. 44.0% (11 of 25) in OBS. Fewer recurrences were seen with RT in patients with adenocarcinoma or adenosquamous histologies relative to others (HR for RT by histology interaction = 0.23, 90% CI = 0.07 to 0.74, p = 0.019). After an extensive follow-up period, 67 deaths have occurred: 27 RT patients and 40 OBS patients. The improvement in overall survival (HR = 0.70, 90% CI = 0.45 to 1.05, p = 0.074) with RT did not reach statistical significance. Pelvic radiotherapy after radical surgery significantly reduces the risk of recurrence and prolongs progression-free survival in women with Stage IB cervical cancer. RT appears to be particularly beneficial for patients with adenocarcinoma or adenosquamous histologies. Circumstances that may have influenced the overall survival differences are considered.

CD004635

The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Data regarding adverse effects of this therapy on the mother or fetus are not available at present.

Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis.

To examine whether ultralong GnRH analog (GnRH-a) therapy after surgical treatment of endometriosis and before ART influences the pregnancy rate. Prospective, randomized, controlled study. University clinic for reproductive medicine and gynecologic endocrinology. One hundred ten patients with stage II to IV endometriosis according to ASRM criteria. Fifty-five patients received GnRH-a for 6 months after surgery and subsequently underwent up to 3 cycles of ART, and 55 patients received 3 cycles of ART alone immediately after surgery. Clinical pregnancy rates. The pregnancy rate per patient was higher among patients who received follow-up treatment with GnRH-a. The same results were found in patients with stage III or IV endometriosis who were undergoing IUI or IVF/ICSI. Ultralong GnRH-a therapy increases the pregnancy rate of ART in patients with severe endometriosis.

CD004635

The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Data regarding adverse effects of this therapy on the mother or fetus are not available at present.

Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis.

To evaluate the effect of a 3-month course of GnRH agonist administered immediately before IVF-ET in infertile patients with endometriosis. Prospective, randomized trial. Three tertiary care assisted reproductive technology programs. IVF-ET candidates with surgically confirmed endometriosis. Twenty-five patients received three courses of a long-acting GnRH agonist, 3.75 mg i.m. every 28 days, followed by standard controlled ovarian hyperstimulation. Twenty-six patients received standard controlled ovarian hyperstimulation with mid-luteal phase GnRH agonist down-regulation or microdose flare regimens. Response to controlled ovarian hyperstimulation, ongoing pregnancy rates per cycle, group implantation rates, and implantation rate per embryo transfer procedure. The extent of surgically confirmed endometriosis was greater in patients who received the long-acting GnRH regimen for 3 months before IVF-ET. The groups did not differ significantly in terms of dose or duration of gonadotropin stimulation, number of oocytes retrieved, fertilization rate, or number of embryos transferred. Patients who received the long-acting GnRH regimen had significantly higher ongoing pregnancy rates (80% vs. 53.85%) and a trend toward higher implantation rates (42.68% vs. 30.38%). Prolonged use of GnRH agonist before IVF-ET in patients with endometriosis resulted in significantly higher ongoing pregnancy rates than did standard controlled ovarian hyperstimulation regimens. No deleterious effect on ovarian response was observed.

CD004635

The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Data regarding adverse effects of this therapy on the mother or fetus are not available at present.

The impact of long-term gonadotropin-releasing hormone analogue treatment on preclinical abortions in patients with severe endometriosis undergoing in vitro fertilization-embryo transfer.

To examine the relationship between endometriosis and preclinical abortions and to evaluate the effect of gonadotropin-releasing hormone analogue (GnRH-a) therapy on these pregnancies. Of 67 women with severe endometriosis referred to us for in vitro fertilization-embryo transfer (IVF-ET), 32 underwent ovarian stimulation for oocyte retrieval with menotropins (protocol A), whereas the other 35 were admitted for the procedure after a 6-month period of hormonal suppression with a GnRH agonist (protocol B). The clinical impact of the preclinical and clinical pregnancies in both treatment protocols were evaluated on the basis of oocyte classification and embryo quality score. All patients were treated in our IVF Unit. Clinical pregnancy was used as our main outcome measure of success. A significantly higher number of preclinical pregnancies (P less than 0.0001) occurred in patients treated by protocol A. After GnRH-a treatment, the preclinical pregnancy rate declined significantly (P less than 0.0001), whereas the clinical pregnancy rate per cycle and per transfer rose significantly (P less than 0.0001 and P less than 0.0001, respectively). Furthermore, clinical pregnancies had a significantly better mean embryo quality score in comparison with preclinical pregnancies (P less than 0.0001). It is concluded that combining GnRH-a therapy before IVF-ET provides an improved treatment modality for preclinical abortions and infertility associated with severe endometriosis.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Contribution of early intensive prolonged pelvic floor exercises on urinary continence recovery after bladder neck-sparing radical prostatectomy: results of a prospective controlled randomized trial.

In this prospective controlled randomized trial we assessed the effects of early, intensive, prolonged pelvic floor exercises (PFE) on urinary incontinence following bladder neck (BN) sparing RRP. A sample of 152 patients with localized prostate cancer underwent RRP with BN preservation. Out of this group we randomized 107 incontinent patients into 2 groups. We considered incontinent patients with 24 hr Pad test >2 g. The T group received instructions regarding an intensive program of PFE, from 7 days after catheter removal for as long as any degree of incontinence persisted, within a period of 1 year. The control (C) group did not receive instructions. The outcome was assessed using the 24 hr Pad test, a visual analogue scale (VAS) and a single question of QoL. Results at baseline and at 1, 3, 6, and 12 months were available for 54 and 40 patients, respectively. The overall spontaneous continence rate after catheter removal was 23.6%. The proportion of men still incontinent was significantly higher in the C group than treatment (T) group at 1 (97.5% vs. 83.3%; P = 0.04), 3 (77.5% vs. 53.7%; P = 0.03), 6 (60% vs. 33.3%; P = 0.01), and 12 months (52.5% vs. 16.6%; P < 0.01). Similarly, the VAS and the response to the QoL question at 12 months significantly differed between the two groups (P = 0.01 and 0.03, respectively). Our study suggests that early intensive prolonged PFE can further increase the number of continent patients and this improvement persists in the first 12 months. The second 6 months following surgery are still useful to recovery. (c) 2007 Wiley-Liss, Inc.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Comparative study of effects of extracorporeal magnetic innervation versus electrical stimulation for urinary incontinence after radical prostatectomy.

To perform a randomized comparative study to investigate the clinical effects of extracorporeal magnetic innervation (ExMI) and functional electrical stimulation (FES) on urinary incontinence after retropubic radical prostatectomy. Thirty-six patients with urinary incontinence after radical prostatectomy were randomly assigned to three groups (12 patients each in the FES, ExMI, and control groups). For FES, an anal electrode was used. Pulses of 20-Hz square waves at a 300-micros pulse duration were used for 15 minutes twice daily for 1 month. For ExMI, the Neocontrol system was used. The treatment sessions were for 20 minutes, twice a week for 2 months. The frequency of the pulse field was 10 Hz for 10 minutes, followed by a second treatment at 50 Hz for 10 minutes. For the control group, only pelvic floor muscle exercises were performed. Objective measures included bladder diaries, 24-hour pad weight testing, and a quality-of-life survey, at 1, 2, and 4 weeks and 2, 3, 4, 5, and 6 months after removing the catheter. The leakage weight during the 24 hours after removing the catheter was 684, 698, and 664 g for the FES, ExMI, and control groups, respectively. At 1 month, it was 72, 83, and 175 g (FES versus control, P <0.05) and at 2 months was 54, 18, and 92 g (ExMI versus control, P <0.05) in the FES, ExMI, and control groups, respectively. Finally, 6 months later, the average 24-hour leakage weight was less than 10 g in all groups. Quality-of-life measures decreased after surgery, but gradually improved over time in all groups. No complications were noted in any of the groups. ExMI and FES therapies offered earlier continence compared with the control group after radical prostatectomy. We consider ExMI and FES to be recommendable options for patients who want quick improvement of postoperative urinary incontinence.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

[Randomized study on urinary continence after radical prostatectomy with previous kinesic perineal physiotherapy].

Urinary incontinence is one of the main complications after radical prostatectomy (RP). Preoperative kinetic physiotherapy could be useful as a preventive treatment of these complication. The objective of this work is to demonstrate the usefulness of preoperative perineal kinetic physiotherapy for early recovery of urinary continence after radical prostatectomy. Randomized controlled clinical trial. 38 patients were divided into groups of 19 before radical prostatectomy. The first group (K) received preoperative kinesic treatment whereas the second group (NK) did not (control group). Urinary continence was evaluated at 14, 30 and 60 days after catheter retrieval. There were not epidemiological or tumor biology differences between groups. The percentages of continent patients in group K at 14, 30 and 60 days were 47.36%, 47.36% and 78.9% respectively, whereas in the NK group where 47.36%, 47.36%, and 89.4% respectively (p > 0.05). Kinesic perineal exercises before radical prostatectomy did not diminish the times of urinary continence recovery or its appearance.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

The recovery of urinary continence after radical retropubic prostatectomy: a randomized trial comparing the effect of physiotherapist-guided pelvic floor muscle exercises with guidance by an instruction folder only.

To compare the effect on the recovery of incontinence after retropubic radical prostatectomy (RRP) of intensive physiotherapist-guided pelvic floor muscle exercises (PG-PFME) in addition to an information folder, with PFME explained to patients by an information folder only (F-PFME), and to determine independent predictors of failure to regain continence after RRP. We postulated that a 10% increase in the proportion of men who regained continence at 6 months with PG-PFME compared with men treated with F-PFME only would constitute a clinically relevant effect. To show statistical significance of this difference with a power of 80%, 96 men should be randomized to each of the two arms. One day before operation, all patients received verbal instruction and an information folder on PFME. Patients randomized to the F-PFME arm received no further physiotherapist guidance, whereas those in the PG-PFME arm received a maximum of nine sessions with the physiotherapist. The men underwent a 1-h pad-test at 1, 12 and 26 weeks, and a 24-h pad-test at 1, 4, 8, 12 and 26 weeks after catheter removal. We defined 'continence' as urine loss of <1 g at the 1-h and <4 g at the 24-h pad-test. During the 2-year recruitment period, the number of patients randomized fell short of the target determined by the sample size calculation, because of limitations of resources and unexpected changes in treatment preferences. Despite this, we analysed the data. Of the 82 randomized patients, 70 completed the study. Of these, 34 and 36 men had been assigned to the PG-PFME and the F-PFME group, respectively. At 6 months after RRP, 10 (30%) and nine (27%) men were completely dry on both the 1-h and 24-h pad-test in the PG-PFME and the F-PFME group, respectively (difference not significant). In a multivariate analysis the amount of urine loss at 1 week after catheter removal seemed to be an independent prognostic factor for failure to regain continence. PG-PFME seems to have no beneficial effect on the recovery of continence within the first 6 months after RRP, over an instruction folder-guided approach. However, due to under-powering there is a high risk of type II error. Nevertheless, these findings add to the knowledge base for availability in meta-analyses and can serve as a starting point for the design of new randomized studies.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Early recovery of urinary continence after radical prostatectomy using early pelvic floor electrical stimulation and biofeedback associated treatment.

We analyzed the benefit of the early combined use of functional pelvic floor electrical stimulation and biofeedback in terms of time to recovery and rate of continence after radical prostatectomy. A total of 60 consecutive patients who underwent radical prostatectomy were included in the study. Patients were prospectively randomized to a treatment group (group 1) vs a control group (group 2). In group 1 a program of pelvic floor electrical stimulation plus biofeedback began 7 days after catheter removal, twice a week for 6 weeks. Each of the 12 treatment sessions was composed of biofeedback (15 minutes) followed by pelvic floor electrical stimulation (20 minutes). The evaluation of continence was performed at time 0, at 2 and 4 weeks, and at 2, 3, 4, 5 and 6 months during followup. Evaluations were performed using the 24-hour pad test and the incontinence section of the International Continence Society questionnaire. The mean leakage weight became significantly lower (p <0.05) in group 1 than in group 2 starting at 4 weeks until 6 months of followup. A significant difference (p <0.05) between groups 1 and 2 in terms of percentage of continent patients was achieved from 4 weeks (63.3% group 1 and 30.0% group 2) to 6 months (96.7% group 1 and 66.7% group 2). Early, noninvasive physical treatment with biofeedback and pelvic floor electrical stimulation has a significant positive impact on the early recovery of urinary continence after radical prostatectomy.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Editorial comment on: does physiotherapist-guided pelvic floor muscle training reduce urinary incontinence after radical prostatectomy? A randomised controlled trial.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Effect of preoperative biofeedback/pelvic floor training on continence in men undergoing radical prostatectomy.

To determine whether preoperative biofeedback training improves urinary continence overall or the rate of return of continence in men undergoing radical prostatectomy. One hundred men scheduled to undergo radical prostatectomy were randomized to receive graded pelvic muscle exercise training with biofeedback 2 to 4 weeks before surgery or to a control group performing pelvic muscle exercises without biofeedback. The biofeedback group was instructed to continue exercises four times per day until surgery and to resume exercises when the urethral catheter was removed following surgery. The control group received written and brief verbal instructions in pelvic muscle exercises before surgery and again after catheter removal. Urinary continence was assessed by personal or phone interviews. Six months following surgery, the continence rates, as defined by the use of one pad or less per day, were 94% (44 of 47) and 96% (48 of 50) in the biofeedback and control groups, respectively (P = 0.596). Also, the rate of return as determined at time points 1, 2, 3, and 4 months after surgery was not significantly different between the two groups. Preoperative biofeedback training did not improve the outcome of pelvic muscle exercises on overall continence or the rate of return of urinary control in men undergoing radical prostatectomy.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

What it would take for men to attend and benefit from support groups after prostatectomy for prostate cancer: a problem-solving approach.

Twenty-nine incontinent prostate cancer patients learned Pelvic Floor Muscle Exercises through biofeedback and were randomly assigned to a control group or a support group entailing six meetings over 3 months. The obtained consent rate (50%) is much higher than the previously reported rate for men (13%). The reasons for refusal were mainly due to actual barriers (48%) and less frequently due to psychological concerns (10.3%). Most support group participants (71.5%) attended five to six group meetings. The findings suggest that men are willing to attend support groups that focus on solving problems and that social supports help men improve continence and quality of life.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Return to continence after radical retropubic prostatectomy: a randomized trial of verbal and written instructions versus therapist-directed pelvic floor muscle therapy.

To test the effectiveness of weekly postoperative pelvic floor muscle training (PFMT) versus supportive telephone contact by a urology nurse for men at 4 weeks after radical prostatectomy. This was a randomized controlled trial in three Canadian centers. At 4 weeks after surgery, standardized verbal and written instruction about PFMT was provided to all subjects. Randomization occurred after initial instruction. Continence was defined as 8 g or less of urine loss on a 24-hour pad test. Primary outcome was grams of urine loss on pad test; secondary outcomes were International Prostate Symptom Score (IPSS), Incontinence Impact Questionnaire (IIQ-7) score, cost, and perception of urine loss as a problem. Data were obtained at baseline (preoperatively) and at weeks 4, 8, 12, 16, and 28 and 1 year after surgery. A total of 216 men were enrolled; 11 were dry or withdrew at 4 weeks. Ninety-nine were randomized to the control group and 106 to the treatment group. There were no group differences at baseline for prostate-specific antigen level (mean [standard deviation] 8.4 [10.4] ng/mL; 7.6 [4.6] ng/mL), Gleason score (6.3 [0.86]), IPSS, IIQ-7 score, pad test, or voiding diary. At 8 weeks 23% of the control group and 20% of the treatment group were continent; at 12 weeks, 28% and 32%; 16 weeks, 40% and 44%; 28 weeks, 50% and 47%; and at 52 weeks, 64% and 60%, respectively. There were no significant differences between groups at any time point for the outcome variables. Verbal instruction and written information with telephone support seemed to be as effective as intensive PFMT. Less-intense therapy may be more cost-effective.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Urinary incontinence in men after formal one-to-one pelvic-floor muscle training following radical prostatectomy or transurethral resection of the prostate (MAPS): two parallel randomised controlled trials.

Urinary incontinence is common immediately after prostate surgery. Men are often advised to do pelvic-floor exercises, but evidence to support this is inconclusive. Our aim was to establish if formal one-to-one pelvic floor muscle training reduces incontinence. We undertook two randomised trials in men in the UK who were incontinent 6 weeks after radical prostatectomy (trial 1) or transurethral resection of the prostate (TURP; trial 2) to compare four sessions with a therapist over 3 months with standard care and lifestyle advice only. Randomisation was by remote computer allocation. Our primary endpoints, collected via postal questionnaires, were participants' reports of urinary incontinence and incremental cost per quality-adjusted life year (QALY) after 12 months. Group assignment was masked from outcome assessors, but this masking was not possible for participants or caregivers. We used intention-to-treat analyses to compare the primary outcome at 12 months. This study is registered, number ISRCTN87696430. In the intervention group in trial 1, the rate of urinary incontinence at 12 months (148 [76%] of 196) was not significantly different from the control group (151 [77%] of 195; absolute risk difference [RD] -1·9%, 95% CI -10 to 6). In trial 2, the difference in the rate of urinary incontinence at 12 months (126 [65%] of 194) from the control group was not significant (125 [62%] of 203; RD 3·4%, 95% CI -6 to 13). Adjusting for minimisation factors or doing treatment-received analyses did not change these results in either trial. No adverse effects were reported. In both trials, the intervention resulted in higher mean costs per patient (£180 and £209 respectively) but we did not identify evidence of an economically important difference in QALYs (0·002 [95% CI -0·027 to 0·023] and -0·00003 [-0·026 to 0·026]). In settings where information about pelvic-floor exercise is widely available, one-to-one conservative physical therapy for men who are incontinent after prostate surgery is unlikely to be effective or cost effective. The high rates of persisting incontinence after 12 months suggest a substantial unrecognised and unmet need for management in these men. National Institute of Health Research, Health Technology Assessment (NIHR HTA) Programme. Copyright © 2011 Elsevier Ltd. All rights reserved.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Effect of pelvic-floor re-education on duration and degree of incontinence after radical prostatectomy: a randomised controlled trial.

Urinary incontinence is a common long-term complication after radical prostatectomy. Spontaneous recovery of normal urinary control after surgery can take 1-2 years. We aimed to investigate whether there was any beneficial effect of pelvic-floor re-education for patients with urinary incontinence as a result of radical prostatectomy. 102 consecutive incontinent patients who had had radical retropubic prostatectomy for clinically localised prostate cancer and who could comply with the ambulatory treatment schedule in our hospital were randomised, after catheter removal, into a treatment group (n=50) and a control group (n=52). Patients in the treatment group took part in a pelvic-floor re-education programme for as long as they were incontinent, and for a maximum of 1 year. The control group received placebo therapy. The primary endpoint was continence rate at 3 months. Incontinence was assessed objectively with the 1 h and 24 h pad tests and subjectively by the visual analogue scale. The groups were analysed on an intention-to-treat basis by ANOVA and chi2-test. In the treatment group continence was achieved after 3 months in 43 (88%) of 48 patients. In the control group, continence returned after 3 months in 29 (56%) of 52 patients. At 1 year, the difference in proportion between treatment and control group was 14% (95% CI 2-27). In the treatment group improvement in both duration (log-rank test, p=0.0001) and degree of incontinence (Wald test, p=0.0010) was significantly better than in the control group. Pelvic-floor re-education should be considered as a first-line option in curing incontinence after radical prostatectomy.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Comparison of behavior therapy methods for urinary incontinence following prostate surgery: a pilot study.

Americans are living longer. As a result, an increased number of pathologic prostates are being detected and treated. As a consequence of complications from surgical treatment, such as prostatectomy, urinary incontinence may occur. However, it is important to understand urinary continence in the male and the anatomic changes that result with prostatectomy. Having objective measures that are cost-effective and accessible can assist with equaling subjective and objective assessments of continence, as well as determining successful outcomes and the need for more complex behavioral treatments.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Preoperative biofeedback assisted behavioral training to decrease post-prostatectomy incontinence: a randomized, controlled trial.

We tested the effectiveness of preoperative biofeedback assisted behavioral training for decreasing the duration and severity of incontinence, and improving quality of life in the 6 months following radical prostatectomy. We performed a prospective, randomized, controlled trial comparing preoperative behavioral training to usual care. The volunteer sample included 125 men 53 to 68 years old who elected radical prostatectomy for prostate cancer. Patients were stratified according to age and tumor differentiation, and randomized to 1 preoperative session of biofeedback assisted behavioral training plus daily home exercise or a usual care control condition, consisting of simple postoperative instructions to interrupt the urinary stream. The main outcome measurements were duration of incontinence (time to continence), as derived from bladder diaries, incontinence severity (the proportion with severe/continual leakage), pad use, Incontinence Impact Questionnaire, psychological distress (Hopkins Symptom Checklist) and health related quality of life (Medical Outcomes Study Short Form Health Survey). Preoperative behavioral training significantly decreased time to continence (p = 0.03) and the proportion of patients with severe/continual leakage at the 6-month end point (5.9% vs 19.6%, p = 0.04). There were also significant differences between the groups for self-reported urine loss with coughing (22.0% vs 51.1%, p = 0.003), sneezing (26.0% vs 48.9%, p = 0.02) and getting up from lying down (14.0% vs 31.9%, p = 0.04). No differences were found on return to work and usual activities or quality of life measures. Preoperative behavioral training can hasten the recovery of urine control and decrease the severity of incontinence following radical prostatectomy.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Pelvic floor muscle training before transurethral resection of the prostate: a randomized, controlled, blinded study.

OBJECTIVE To evaluate the effect of preoperative pelvic floor muscle training (PFMT) in men scheduled for transurethral resection of the prostate (TURP) in a randomized, single-blind study. Fifty-eight men with benign prostatic obstruction were included, and 49 completed the study (training group, n=26; control group, n=23). The preoperative training included a 1-h individual lesson, three 1-h group lessons and a home training programme. Postoperatively and before discharge from hospital both groups received verbal instructions regarding PFMT. Pelvic floor muscle function was assessed by anal examination before and 4 weeks after surgery by one physiotherapist who was blinded to the randomization. The primary outcome parameter was the total score on the Danish Prostatic Symptom Score questionnaire. Secondary outcome measures were other subjective and objective voiding and incontinence parameters and four tests of the pelvic floor muscle: function; strength; static endurance; and dynamic endurance. Baseline characteristics were similar in the two groups. Improved static endurance occurred in the training group but not in the control group (p=0.004). Regarding dynamic endurance, a difference in favour of training developed between the groups (p=0.049). Many men produced results that were outside the test scales. At follow-up at 2 and 4 weeks and 3 months there were no differences between the groups in any of the lower urinary tract parameters. Preoperative PFMT produced a significant improvement in pelvic floor muscle endurance after TURP, but clinically relevant storage or voiding improvements did not occur. Pelvic floor muscle assessment tests need to be sex-specific.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

The role of pelvic floor exercises on post-prostatectomy incontinence.

Post-radical prostatectomy incontinence occurs in 0.5% to 87% of patients. This condition may be attributable to intrinsic sphincteric deficiency, and/or detrusor abnormalities. Previous studies of pelvic floor exercise (PFE) for improving post-prostatectomy incontinence have shown mixed results. We determined whether preoperative and early postoperative biofeedback enhanced PFE with a dedicated physical therapist would improve the early return of urinary incontinence. A total of 38 consecutive patients undergoing radical prostatectomy from November 1998 to June 1999 were randomly assigned to a control or a treatment group. The treatment group of 19 patients was referred to physical therapy and underwent PFE sessions before and after surgery. Patients were also given instructions to continue PFE at home twice daily after surgery. The control group of 19 men underwent surgery without formal PFE instructions. All patients completed postoperative urinary incontinence questionnaires at 6, 12, 16, 20, 28 and 52 weeks. Incontinence was measured by the number of pads used with 0 or 1 daily defined as continence. Overall 66% of the patients were continent at 16 weeks. A greater fraction of the treatment group regained urinary continence earlier compared with the control group at 12 weeks (p <0.05). Three control and 2 treatment group patients had severe incontinence (greater than 3 pads daily) at 16 and 52 weeks. Of all patients 82% regained continence by 52 weeks. PFE therapy instituted prior to radical prostatectomy aids in the earlier achievement of urinary incontinence. However, PFE has limited benefit in patients with severe urinary incontinence 16 weeks after surgery. There is a minimal long-term benefit of PFE training since continence rates at 1 year were similar in the 2 groups.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Pelvic muscle exercise/biofeedback for urinary incontinence after prostatectomy: an education program.

This study tested the effectiveness of pelvic muscle exercise (PME) with biofeedback in reducing the length of time urinary incontinence (UI) was experienced following a radical prostatectomy for localized prostate cancer. Fifty-three men were randomly assigned to an education intervention group or a control group. The education group received instruction in PME/biofeedback and were given a PME protocol to perform three times per week for 12 weeks. The control group did not receive instruction in PME technique. Both groups recorded urine losses in three-day bladder diaries, and 24-hour pad tests were done in weeks 2, 5, 9, and 12 after surgery. Study variables included: 1) length of time urine loss was experienced; 2) episodes and frequency of urine loss; and 3) ounces of urine lost and number of pads used. The PME/biofeedback group regained continence at a mean of 51 days; the non-PME group at 56 days. Although the PME group demonstrated reductions in episodes, frequency, ounces of urine lost by UI, and pad usage, they were not statistically significant. After prostatectomy, men experience UI for periods of one to 80+ days. The use of biofeedback enhances learning PME and skill performance. Bladder diaries and behavioral management techniques (PME) need to be further studied as appropriate treatment methods to assist men in managing UI after cancer surgery.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Pelvic floor exercises, electrical stimulation and biofeedback after radical prostatectomy: results of a prospective randomized trial.

We assessed the effect of pelvic muscle exercises (PMEs), electrical stimulation (ES) and biofeedback (BFB) on urinary incontinence after radical retropubic prostatectomy. We randomized 139 patients who underwent radical retropubic prostatectomy into 3 groups. Group 1 received instructions about postoperative PMEs. Group 2 received the same instructions and ES for 15 minutes twice daily. Patients in group 3 were also treated with BFB for 15 minutes twice daily. Treatment was started immediately after catheter removal and performed for 3 months. The outcome was assessed using the 20-minute pad test and a urine symptom inventory. Results at baseline, and 3 and 12 months postoperatively were available for 139, 120 and 128 (questionnaire), and 116, 79 and 124 (pad test) patients, respectively. An overall subjective spontaneous continence rate (questionnaire) 1 day after catheter removal of 21.4% increased within the first 3 months up to 59.2%. There was no significant difference among the 3 groups. The continence rate increased from 3 to 12 months postoperatively from 59.2% to 85.9%. An overall objective spontaneous continence rate (pad test) 1 day after catheter removal of 32.9% increased within the first 3 months up to 65% and up to 83% after 12 months without any significant difference in all 3 groups. A treatment program of ES and BFB enhanced PMEs did not affect continence after radical prostatectomy after 3 or 12 months. Up to 711 euro can be saved per patient.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Early post-prostatectomy pelvic floor biofeedback.

We determined whether biofeedback enhanced pelvic floor exercises begun 6 weeks after radical prostatectomy improve the early recovery of continence. We randomized 30 patients who underwent radical retropubic prostatectomy into a group that received 5 biofeedback sessions and a control group. Overall 87% of patients were pad-free at 6 months with similar results in the treatment and control groups (86% versus 88%). There was no statistically significant difference in pad test results or voiding diary records in the 2 groups. A treatment program of biofeedback enhanced pelvic floor exercises begun 6 weeks after radical retropubic prostatectomy did not significantly affect continence in this study.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Effectiveness of early pelvic floor rehabilitation treatment for post-prostatectomy incontinence.

Urinary incontinence after radical prostatectomy is a significant clinical problem. In this prospective study we investigate the effectiveness of early pelvic floor muscle training (PFMT) on a large population, that had undergone radical retropubic prostatectomy (RRP) at our department. 300 consecutive patients who had undergone RRP for clinically confined prostate cancer were randomized in two groups after catheter removal. One group of 150 patients took part in a structured PFMT program. This began before discharge and consisted of Kegel exercises. The remaining 150 patients constituted the control group, they were not formally instructed in PFMT. Incontinence was assessed objectively using the 1 hour and 24 hour pad test, as well as with the ICS-Male questionnaire. All patients who were incontinent after 6 months underwent urodynamic evaluation. In the treated group, 19% (29 patients) achieved continence after 1 month, and 94.6% (146 patients) after 6 months. In the control group 8% (12 patients) achieved continence after 1 month, and 65% (97 patients) after 6 months (p<0.001). Patient age did not correlate with continence in the control group (p>0.05), although a significant correlation was revealed within the treated group (p<0.01). Overall, 93.3% of the total population achieved continence after one year. After RRP an early supportive rehabilitation program like PFMT significantly reduces continence recovery time.

CD001843

The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. It seems unlikely that men benefit from one-to-one pelvic floor muscle training therapy after transurethral resection of the prostate (TURP).  Long-term incontinence may be managed by external penile clamp, but there are safety problems.

Impact of early pelvic floor rehabilitation after transurethral resection of the prostate.

We examined the results of teaching pelvic floor muscle exercises (PME) on micturition parameters, urinary incontinence, post-micturition dribbling, and quality of life in patients after transurethral prostatectomy (TURP). Fifty-eight consecutive patients who were selected to undergo TURP for benign prostatic hyperplasia (BPH) were admitted into the study: 28 were randomly assigned to a control group (A), 30 formed the investigational group (B) during an initial visit conducted before surgery. In group B patients, perineal exercises were demonstrated in detail, and tested for their correct use via simultaneous rectal and abdominal examination. After the removal of the urethral catheter, these patients were instructed to perform pelvic floor muscle exercises at home and were evaluated before the exercises and at weekly intervals postoperatively. The American Urological Association Symptom Score improved significantly after TURP in both groups. The average quality of life score improved more significantly in group B after TURP, from 5.5 to 1.5 (P < 0.001). The grade of muscle contraction strength after 4 weeks of PME increased from 2.8 to 3.8 in group B (P < 0.01); it was unchanged in the group A. The number of patients with incontinence episodes and post-micturition dribbling was significantly lower in the group B at weeks 1, 2, and 3 (P < 0.01). Our results show that pelvic floor muscle re-education produces a quicker improvement of urinary symptoms and of quality of life in patients after TURP. Its early practice reduces urinary incontinence and post-micturition dribbling in the first postoperative weeks. The exercises are simple and easy to perform in the clinical setting and at home, and therefore should be recommended to all cooperative patients after TURP.

CD007877

There is no reliable evidence from randomised controlled trials to support the effectiveness of haemostatic drugs in reducing mortality or disability in patients with TBI. New randomised controlled trials assessing the effects of haemostatic drugs in TBI patients should be conducted. These trials should be large enough to detect clinically plausible treatment effects.

Safety of rFVIIa in hemodynamically unstable polytrauma patients with traumatic brain injury: post hoc analysis of 30 patients from a prospective, randomized, placebo-controlled, double-blind clinical trial.

Trauma is a leading cause of mortality and morbidity, with traumatic brain injury (TBI) and uncontrolled hemorrhage responsible for the majority of these deaths. Recombinant activated factor VIIa (rFVIIa) is being investigated as an adjunctive hemostatic treatment for bleeding refractory to conventional replacement therapy in trauma patients. TBI is a common component of polytrauma injuries. However, the combination of TBI with polytrauma injuries is associated with specific risk factors and treatment modalities somewhat different from those of polytrauma without TBI. Although rFVIIa treatment may offer added potential benefit for patients with combined TBI and polytrauma, its safety in this population has not yet been assessed. We conducted a post hoc sub analysis of patients with TBI and severe blunt polytrauma enrolled into a prospective, international, double-blind, randomized, placebo-controlled study. A post hoc analysis of study data was performed for 143 patients with severe blunt trauma enrolled in a prospective, randomized, placebo-controlled study, evaluating the safety and efficacy of intravenous rFVIIa (200 + 100 + 100 microg/kg) or placebo, to identify patients with a computed tomography (CT) diagnosis of TBI. The incidences of ventilator-free days, intensive care unit-free days, and thromboembolic, serious, and adverse events within the 30-day study period were assessed in this cohort. Thirty polytrauma patients (placebo, n = 13; rFVIIa, n = 17) were identified as having TBI on CT. No significant differences in rates of mortality (placebo, n = 6, 46%, 90% confidence interval (CI): 22% to 71%; rFVIIa, n = 5, 29%, 90% CI: 12% to 56%; P = 0.19), in median numbers of intensive care unit-free days (placebo = 0, rFVIIa = 3; P = 0.26) or ventilator-free days (placebo = 0, rFVIIa = 10; P = 0.19), or in rates of thromboembolic adverse events (placebo, 15%, 90% CI: 3% to 51%; rFVIIa, 0%, 90% CI: 0% to 53%; P = 0.18) or serious adverse events (placebo, 92%, 90% CI: 68% to 98%; rFVIIa, 82%, 90% CI: 60% to 92%; P = 0.61) were observed between treatment groups. The use of a total dose of 400 (200 + 100 + 100) microg/kg rFVIIa in this group of hemodynamically unstable polytrauma patients with TBI was not associated with an increased risk of mortality or with thromboembolic or adverse events.

CD007877

There is no reliable evidence from randomised controlled trials to support the effectiveness of haemostatic drugs in reducing mortality or disability in patients with TBI. New randomised controlled trials assessing the effects of haemostatic drugs in TBI patients should be conducted. These trials should be large enough to detect clinically plausible treatment effects.

Progression of traumatic intracerebral hemorrhage: a prospective observational study.

ABSTRACT Preliminary evidence has shown that intracerebral hemorrhages, either spontaneous (sICH) or traumatic (tICH) often expand over time. An association between hemorrhage expansion and clinical outcomes has been described for sICH. The intent of this prospective, observational study was to characterize the temporal profile of hemorrhage progression, as measured by serial computed tomography (CT) scanning, with the aim of better understanding the natural course of hemorrhage progression in tICH. There was also a desire to document the baseline adverse event (AE) profile in this patient group. An important motive for performing this study was to set the stage for subsequent studies that will examine the role of a new systemic hemostatic agent in tICH. Subjects were enrolled if they had tICH lesions of at least 2 mL on a baseline CT scan obtained within 6 h of a head injury. CT scans were repeated at 24 and 72 h. Clinical outcomes and pre-defined AEs were documented. The data showed that 51% of the subjects demonstrated an increase in tICH volume, and that most of the increase occurred early. In addition, larger hematomas exhibited the greatest expansion. Thromboembolic complications were identified in 13% of subjects. This study demonstrates that tICH expansion between the baseline and 24-h CT scans occurred in approximately half of the subjects. The earlier after injury that the initial CT scan is obtained, the greater is the likelihood that the hematoma will expand on subsequent scans. The time frame during which hemorrhagic expansion occurs provides an opportunity for early intervention to limit a process with adverse prognostic implications.

CD004597

There were insufficient data to establish whether oral EPA was better than placebo. Comparisons of EPA combined with a protein energy supplementation versus a protein energy supplementation (without EPA) in the presence of an appetite stimulant (Megestrol Acetate) provided no evidence that EPA improves symptoms associated with the cachexia syndrome often seen in patients with advanced cancer.

Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study.

To determine whether high doses of fish oil, administered over 2 weeks, improve symptoms in patients with advanced cancer and decreased weight and appetite. Sixty patients were randomly assigned to fish oil capsules or placebo. Appetite, tiredness, nausea, well-being, caloric intake, nutritional status, and function were prospectively assessed at days 1 and 14. The baseline weight loss was 16 +/- 11 and 16 +/- 8 kg in the fish oil (n = 30) and placebo (n = 30) group respectively, whereas the baseline appetite (0 mm = best and 10 mm = worst) was 58 +/- 24 mm and 67 +/- 19 mm, respectively (P = not significant). The mean daily dose was 10 +/- 4 (fish oil group) and 9 +/- 3 (placebo group) capsules, which provided 1.8 g of eicosapentaenoic acid and 1.2 g of docosahexaenoic acid in the fish oil group. No significant differences in symptomatic or nutritional parameters were found (P <.05), and there was no correlation between changes in different variables between days 1 and 14 and the fish oil doses. Finally, the majority of the patients were not able to swallow more than 10 fish oil capsules per day, mainly because of burping and aftertaste. Fish oil did not significantly influence appetite, tiredness, nausea, well-being, caloric intake, nutritional status, or function after 2 weeks compared with placebo in patients with advanced cancer and loss of both weight and appetite.

CD004597

There were insufficient data to establish whether oral EPA was better than placebo. Comparisons of EPA combined with a protein energy supplementation versus a protein energy supplementation (without EPA) in the presence of an appetite stimulant (Megestrol Acetate) provided no evidence that EPA improves symptoms associated with the cachexia syndrome often seen in patients with advanced cancer.

Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial.

N-3 fatty acids, especially eicosapentaenoic acid (EPA), may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer. A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein +/- 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial. At enrolment, patients' mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight (delta weight E: -0.25 kg/month versus C: -0.37 kg/month; p = 0.74) and LBM (Delta LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group. Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss. Post hoc dose-response analysis suggests that if taken in sufficient quantity, only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight, lean tissue, and improved quality of life. Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia.

CD004597

There were insufficient data to establish whether oral EPA was better than placebo. Comparisons of EPA combined with a protein energy supplementation versus a protein energy supplementation (without EPA) in the presence of an appetite stimulant (Megestrol Acetate) provided no evidence that EPA improves symptoms associated with the cachexia syndrome often seen in patients with advanced cancer.

An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort.

Studies suggest eicosapentaenoic acid (EPA), an omega-3 fatty acid, augments weight, appetite, and survival in cancer-associated wasting. This study determined whether an EPA supplement-administered alone or with megestrol acetate (MA)-was more effective than MA. Four hundred twenty-one assessable patients with cancer-associated wasting were randomly assigned to an EPA supplement 1.09 g administered bid plus placebo; MA liquid suspension 600 mg/d plus an isocaloric, isonitrogenous supplement administered twice a day; or both. Eligible patients reported a 5-lb, 2-month weight loss and/or intake of less than 20 calories/kg/d. A smaller percentage taking the EPA supplement gained >or= 10% of baseline weight compared with those taking MA: 6% v 18%, respectively (P =.004). Combination therapy resulted in weight gain of >or= 10% in 11% of patients (P =.17 across all arms). The percentage of patients with appetite improvement (North Central Cancer Treatment Group Questionnaire) was not statistically different: 63%, 69%, and 66%, in EPA-, MA-, and combination-treated arms, respectively (P =.69). In contrast, 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm, with scores of 40, 55, and 55 in EPA-, MA-, and combination-treated arms, respectively (P =.004). Survival was not significantly different among arms. Global quality of life was not significantly different among groups. With the exception of increased impotence in MA-treated patients, toxicity was comparable. This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone.

CD004597

There were insufficient data to establish whether oral EPA was better than placebo. Comparisons of EPA combined with a protein energy supplementation versus a protein energy supplementation (without EPA) in the presence of an appetite stimulant (Megestrol Acetate) provided no evidence that EPA improves symptoms associated with the cachexia syndrome often seen in patients with advanced cancer.

Eicosapentaenoic acid ethyl ester supplementation in cachectic cancer patients and healthy subjects: effects on lipolysis and lipid oxidation.

Recent reports suggest that weight loss in cachectic cancer patients may be inhibited by supplementation of the n-3 fatty acid eicosapentaenoic acid (20:5n-3; EPA), presumably due to inhibition of lipolysis. The aim of the present double-blind, randomized trial was to assess whether short-term oral EPA ethyl ester (EE) supplementation inhibits lipolysis and lipid oxidation in weight-losing cancer patients and in healthy subjects. Seventeen weight-losing, cancer patients of different tumor types, and 16 healthy subjects were randomized to receive EPA-EE (6 g/d) or placebo (oleic acid (OA)-EE; 6 g/d) for seven days. At baseline (day 0) and during supplementation (days 2 and 7) whole-body lipolysis and palmitic acid release were measured in the overnight fasting state using [1, 1, 2, 3, 3-(2)H(5)]glycerol and [1-(13)C]palmitic acid. Palmitate oxidation was determined by measuring(13)CO(2)enrichment in expired breath. No significant effects of EPA-EE on whole-body lipolysis, palmitic acid release, or palmitate oxidation were detected in cancer patients nor in healthy subjects in comparison with OA-EE. EPA-EE supplementation reduced plasma-free fatty acid and triacylglycerol concentrations significantly in healthy subjects but not in cancer patients. We conclude that supplementation of EPA-EE does not significantly inhibit lipolysis or lipid oxidation in weight-losing cancer patients or in healthy subjects during short-term supplementation when using OA-EE as a placebo supplement. Copyright 2000 Harcourt Publishers Ltd.

CD004597

There were insufficient data to establish whether oral EPA was better than placebo. Comparisons of EPA combined with a protein energy supplementation versus a protein energy supplementation (without EPA) in the presence of an appetite stimulant (Megestrol Acetate) provided no evidence that EPA improves symptoms associated with the cachexia syndrome often seen in patients with advanced cancer.

Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial.

The aim of the current prospective, randomized control study was to investigate the effect of dietary omega-3 polyunsaturated fatty acids plus vitamin E on the immune status and survival of well-nourished and malnourished patients with generalized malignancy. Sixty patients with generalized solid tumors were randomized to receive dietary supplementation with either fish oil (18 g of omega-3 polyunsaturated fatty acids, PUFA) or placebo daily until death. Each group included 15 well-nourished and 15 malnourished patients. The authors measured total T cells, T-helper cells, T-suppressor cells, natural killer cells, and the synthesis of interleukin-1, interleukin-6, and tumor necrosis factor by peripheral blood mononuclear cells before and on Day 40 of fish oil supplementation. Karnofsky performance status, nutritional state, and survival were also estimated. The ratio of T-helper cells to T-suppressor cells was significantly lower in malnourished patients. Omega-3 PUFA had a considerable immunomodulating effect by increasing this ratio in the subgroup of malnourished patients. There were no significant differences in cytokine production among the various groups, except for a decrease in tumor necrosis factor production in malnourished cancer patients, which was restored by omega-3 fatty acids. The mean survival was significantly higher for the subgroup of well-nourished patients in both groups, whereas omega-3 fatty acids prolonged the survival of all the patients. Malnutrition appears to be an important predictor of survival for patients with end stage malignant disease. Omega-3 polyunsaturated fatty acids had a significant immunomodulating effect and seemed to prolong the survival of malnourished patients with generalized malignancy.