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CD004833

One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

Comparison of topical phenytoin with normal saline in the treatment of chronic trophic ulcers in leprosy.

Trophic ulceration, one of the most common complications of leprosy, is disabling, distressing, and demoralizing for the patient. The wound healing effects of topical phenytoin powder were compared with those of normal saline in a controlled in-patient study of 100 patients with 110 trophic leprosy ulcers of varying chronicity, over a 4-week study period. Fifty patients were assigned to the topical phenytoin group and 50 to saline therapy group. Ten patients had two ulcers each, and, in these cases, one ulcer was treated with phenytoin and the other with saline. Over the 4-week treatment period healthy granulation tissue appeared earlier, and mean percentage of ulcer volume reduction was greater, in the phenytoin group (72.1 +/- 19.9% versus 55.5 +/- 21.6%) compared with the control group. This difference was statistically significant at the level of P < 0.001. Phenytoin appears to be a useful agent for the promotion of healing of trophic leprosy ulcers.

CD004833

One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

Treatment of leprosy wounds with adhesive zinc tape.

CD004833

One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

Topical phenytoin suspension and normal saline in the treatment of leprosy trophic ulcers: a randomized, double-blind, comparative study.

To evaluate and compare two strengths of topical phenytoin sodium suspension (2% and 4%) with normal saline in the healing of acute trophic ulcers in leprosy patients. A prospective, parallel, double-blind, randomized study was conducted in 45 leprosy inpatients with acute trophic ulcers. Patients were randomized to receive 2%, 4% or normal saline dressing on their ulcers once daily for 4 weeks. Efficacy parameters such as a reduction in the surface area of the ulcer, bacterial culture of the ulcer swab, appearance of healthy granulation tissue, cessation of ulcer discharge and overall gradation of clinical healing and safety were assessed at weekly intervals. The ulcer area reduction was greater in the 2% and 4% phenytoin groups compared with the normal saline group (p<0.001). Appearance of healthy granulation tissue and cessation of ulcer discharge was also observed earlier in the two phenytoin groups. At the end of 4 weeks, 11 ulcers each had healed completely in both the 2% and 4% phenytoin groups compared with none in the control group. There were no statistical differences between the 2% and 4% phenytoin groups. No side effects were reported by any patient. Topical phenytoin appears to be an effective, safe and cheap therapeutic option for the healing of trophic ulcers in leprosy patients.

CD004833

One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

Treatment of plantar ulcers in leprosy patients in the community with adhesive zinc tape.

CD004833

One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

Use of topical ketanserin for the treatment of ulcers in leprosy patients.

A comparative study was carried out in which 66 leprosy patients with ulcers were randomly divided in two groups of 33 patients each: Group A (experimental group) was treated with ketanserin gel (2%) and group B with clioquinol cream and/or Lassar paste during a three month period. At the end of the study, when ulcer sizes in the two groups were compared, the group treated with topical ketanserin showed superior results (p < 0.001 using Kolmogorov-Smirnov's test). We conclude that the drug is useful as coadjuavant treatment for healing ulcers in these patients.

CD004833

One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

[Effect of zinc oxide tape on plantar ulcers in leprosy patients in Indonesia].

In this investigation the effectiveness was studied of adhesive zinc oxide tape, as additional therapy to the usual application of povidone iodine (10%), for leprosy patients with plantar ulcers in Sulawesi Tengah, Indonesia. The effectiveness (degree of wound healing measured as surface reduction) of this experimental therapy was compared with that of the usual therapy alone. At the same time the influence of the physical activity level on the effectiveness of both therapies was studied. During six weeks 38 leprosy patients with simple ulcers were treated with either one of the therapies. The average wound healing of the experimental group and the control group was 388 mm2 (SD 498) and 260 mm2 (SD 260) respectively. Using the t-test, there was no statistically significant difference in wound healing between the two therapies (p = 1.7). The average wound healing of the experimental group with a high and a low activity level was 342 mm2 (SD 226) and 405 mm2 (SD 571) respectively. The average wound healing of the control group with a high and low activity level was 246 mm2 (SD 289) and 275 mm2 (SD 232) respectively. Using analyses of variance, there was no statistically significant influence on the effectiveness of the therapies (p greater than 0.1). Methodological problems possibly influenced on the results. Different problems which may be encountered during research in third world countries are mentioned.

CD004833

One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

Footwear for farmers affected by leprosy.

CD004833

One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.

Simple plantar ulcers treated by below-knee plaster and moulded double-rocker plaster shoe--a comparative study.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

A randomized trial of Citanest with Octapressin for relief of pain associated with laser vaporization of the cervix.

Fifty women undergoing laser vaporization of the cervix for cervical intraepithelial neoplasia were randomly allocated to one of two groups. In one group the patients received no anaesthesia, in the other the ectocervix was infiltrated with 2 ml of Citanest with Octapressin (prilocaine 3% with 0.03 i.u./ml. of felypressin) immediately before the procedure. The pain experienced by each group was assessed immediately after treatment by visual analogue and verbal rating scales. The pain experienced by those women receiving local anaesthesia was significantly reduced as assessed by the visual analogue scale (P = 0.011) and this reduction was not quite significant by the verbal rating scale (P = 0.06). The Citanest group had less troublesome bleeding but the difference in bleeding between the two groups was not significant.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

The effect of local anaesthetic spray on the pain associated with local anaesthetic injection, prior to biopsy or loop diathermy to the cervix in the outpatient colposcopy clinic.

We evaluated the effectiveness of local anaesthetic spray prior to injection of local anaesthetic before biopsy or large loop excision of the transformation zone of the cervix at colposcopy. This was a prospective, randomised, double-blind placebo-controlled study involving 51 women. Pain or discomfort was measured using a four-point categorical scale and a visual analogue score. Our results show that the use of local anaesthetic spray has no effect on the pain or discomfort experienced by patients having local anaesthetic injections to the cervix, and cannot be recommended.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

Local anesthesia for cryosurgery on the cervix.

Forty-five patients were evaluated in a prospective, randomized study to determine the effectiveness of a local injection of lidocaine in reducing pain during cervical cryosurgery. Study patients received a submucosal cervical injection of 1% lidocaine with a 1:100,000 dilution of epinephrine. Control patients did not receive an injection. Both groups received a single dose of naproxen sodium or ketoprofen prior to the procedure. The patient and the observing nurse recorded the pain experienced with a visual analog scale (VAS). Nurse and patient response for the control and study groups showed a high correlation (r = .573 and P < .01, r = .673 and P < .001, respectively). The mean VAS score recorded for the 26 control patients was 4.27, significantly greater than the mean score for the 19 study patients, 1.16 (P < .001). These findings indicate that a submucosal local injection of lidocaine with epinephrine is effective in reducing pain during cervical cryosurgery.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

Is transcutaneous electrical nerve stimulation of any value during cervical laser treatment?

To assess the value of transcutaneous electrical nerve stimulation (TENS) during cervical laser therapy. Randomized three arm controlled clinical trial comparing (i) TENS, (ii) local anaesthetic and (iii) TENS plus local anaesthetic (direct infiltration of 2% lignocaine and 0.03 iu/ml octopressin). Colposcopy Unit adapted to run randomized trials. 100 women with CIN and no previous experience of cervical surgery. Visual linear analogue pain scores. The median pain score associated with TENS was greater than the score associated with local anaesthesia (23% compared with 17%; P = 0.1). Combining TENS with local anaesthesia did not further reduce pain scores. Although there was considerable consumer satisfaction with TENS it provided no additional pain relieving effect in addition to direct infiltration of lignocaine and it is inferior to lignocaine alone. We are unable to advocate the use of TENS for laser treatment of the cervix.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

A randomised controlled trial comparing two different local anaesthetic injection techniques prior to LLETZ.

The aim of this study was to compare two different anaesthetic injection techniques and assess whether one was less painful than the other when used prior to LLETZ. A total of 60 women undergoing LLETZ were randomised into two groups. The control group received local anaesthesia by deep injection into the substance of the cervix. The study group received an equivalent amount of local anaesthetic but this was injected superficially prior to deep injection into the cervix. Pain was assessed using a visual analogue scale. Women in the study arm experienced less pain than controls during injection of local anaesthetic.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

Efficacy of lignocaine analgesia during treatment to the cervix.

There is no consensus amongst physicians about the need for analgesia when a woman undergoes ablative therapy of the cervix. Many doctors believe that the discomfort felt during such procedures is insubstantial. By means of a randomised double-blind placebo-controlled trial, we have shown that patients experience considerable pain during cold-coagulation treatment of the cervix. We found that intracervical lignocaine leads to a significant (p < 0.01) reduction in this pain.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

The effect of topical 20% benzocaine on pain during loop electrosurgical excision of the cervix.

Our purpose was to evaluate the effect of cervical application of 20% benzocaine on the pain associated with subsequent cervical injection of local anesthetic and tissue excision during the loop electrosurgical excision procedure of the cervix. Fifty consecutive women scheduled for loop electrosurgical excision were randomized by use of computer-generated numbers to receive cervical application of either 20% benzocaine or placebo gel in a double-blinded fashion. A visual analog scale was used to measure the pain associated with both cervical injection of local anesthetic and tissue excision. Lower mean pain scores were associated with the use of benzocaine gel for both anesthetic injection and tissue excision, but these scores did not reach statistical significance in either group. Preoperative cervical application of 20% benzocaine does not appear to reduce the pain associated with either subsequent local anesthetic injection or tissue excision during the loop electrosurgical excision procedure of the cervix.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

A randomised controlled trial to evaluate the effect of self-administered analgesia on women's experience of outpatient treatment at colposcopy.

To evaluate the effect of self-administered isoflurane and desflurane on women's experience of outpatient treatment at colposcopy. A prospective double-blinded randomised controlled trial. A colposcopy clinic serving a regional population. Three hundred and ninety-six women scheduled for treatment of cervical intraepithelial neoplasia (CIN) by large loop excision of the transformation zone (LLETZ). Self-administration of trial gas during a LLETZ procedure. One hundred and ninety-eight women were randomised to use isoflurane and desflurane and 198 to use placebo. Patient satisfaction, pain and anxiety. The mean pain score for cervical surgery was significantly lower for women using isoflurane and desflurane (22.4) than the placebo arm (29.6) (P= 0.003). There was no significant difference between arms in anxiety levels before or after treatment. More women using isoflurane and desflurane (78%) reported 'total helpfulness' of the trial gas than those using placebo (67%) (P= 0.012). A subgroup analysis of trial participants classified as anxious by Hospital Anxiety and Depression Scale (HADS) score at recruitment showed that using isoflurane and desflurane significantly increased total treatment acceptability, helpfulness of the gas and willingness to undergo a similar procedure at six-month follow up. Satisfaction with outpatient treatment at colposcopy is generally high. The main effect of isoflurane and desflurane evaluated in this trial was to reduce pain. It appeared to be effective for women with clinically significant anxiety and could be offered as an alternative to general anaesthesia.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

A double-blind, randomized, placebo-controlled trial of prilocaine and felypressin (Citanest and Octapressin) for the relief of pain associated with cervical biopsy and treatment with the Semm coagulator.

To quantify the anticipated and actual pain experienced in association with preliminary cervical punch biopsies and subsequent ablative treatment with the Semm coagulator, and to test the hypothesis that the intracervical injection of prilocaine with felypressin reduces the intensity of the pain experienced. One hundred consecutive women referred with abnormal cervical smears for colposcopic assessment and considered suitable for treatment with the Semm coagulator were recruited to a double-blind, randomized, prospective, placebo-controlled trial conducted in a colposcopy clinic in a university teaching hospital. Personal particulars were taken and anticipated pain scored. The patients were injected with randomized externally identical vials of prilocaine and felypressin (Citanest and Octapressin) or placebo. After biopsy and treatment, patients scored their actual pain experienced. Pain scores were compared as the main outcome measure. Relative risks with 95% CIs were calculated and compared using the CI Analysis computer programme (Professor Martin J Gardner and the British Medical Journal Version 1.1, copyright 1991). Anticipated pain was greater than the actual pain experienced in both groups. Women receiving the local anesthesia experienced a significantly greater reduction in pain (p < .05) with only 4.3% and 6.7% experiencing moderate pain during biopsy and treatment, respectively. The active drug abolished severe pain. In the placebo group, 44.7% felt mild pain at the most. Intracervical injection of prilocaine and felypressin reduces the intensity of pain experienced in women undergoing cervical biopsy and treatment with the Semm coagulator. Its use is commendable but is not absolutely necessary in all cases.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

A comparison of the side effects of prilocaine with felypressin and lignocaine with adrenaline in large loop excision of the transformation zone of the cervix: results of a randomised trial.

To test the hypothesis that prilocaine with felypressin causes fewer side effects than lignocaine with adrenaline when performing large loop excision of the transformation zone of the cervix. Randomised trial. Colposcopy clinic in a large district general hospital. Two hundred consecutive women undergoing large loop excision of the transformation zone of the cervix. Two different local anaesthetic combinations (prilocaine with felypressin and lignocaine with adrenaline) were compared in women undergoing large loop excision of the transformation zone. Prospective collection of clinical and treatment data was undertaken with scoring using an ordinal scale of pain experienced by the women during the procedure. Peri-operative blood loss and any side effects were also recorded. Side effects associated with the local anaesthetic agents. Lignocaine with adrenaline resulted in less blood loss (P = 0.006) but was more likely to cause side effects, such as feeling faint (P = 0.017) and shaking (P < 0.001). Prilocaine with felypressin causes fewer side effects than lignocaine with adrenaline and is therefore the preferred local anaesthetic combination for large loop excision of the transformation zone.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

A randomized trial of the use of cocaine spray to provide pain relief during laser vaporization of the cervix.

In a double-blind trial, 50 patients undergoing laser vaporization of the cervix for cervical intraepithelial neoplasia were randomly allocated to one of two groups. One group had the cervix sprayed with 3-4 ml of a solution containing 10% cocaine, the other a placebo solution during the laser treatment. Women in the cocaine group had significantly less pain as assessed by a visual analogue scale (P less than 0.001) and by a verbal rating scale (P = 0.002). The cocaine group also had less blood loss (P = 0.001) as assessed subjectively by the operator.

CD006120

Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

Pain evaluation during carbon dioxide laser vaporization for cervical intraepithelial neoplasia: a randomized trial.

63 pts affected by CIN of various degrees were randomly divided into 3 groups in order to evaluate the pain experienced during laser vaporization of the lesion. All pts were premenopausal and ages ranged between 19 and 39 years. 21 pts received Naproxene Sodium (550 mg) 30 minutes before surgery; 21 pts received placebo and 21 pts received no drug. Laser vaporization was performed with a Coherent System 451 CO2 laser with a power setting of 28 W/cm2 and a spot size of 1.8 mm. The severity of pain was assessed by means of a Visual Analogue Scale. The mean VAS value was 19 for the group treated with Naproxene Sodium; the mean VAS value was 20 for the placebo group and 23 for the group which received no pre-operative drug. Analysis of data from the 3 groups showed no statistically significant difference. Analgesia or anaesthesia before laser surgery for CIN is not a necessity.

CD005511

The finding that healing rates can be higher for cases treated surgically as compared to those treated non-surgically, at least in the short term, is based on two RCTs only. A single RCT reported that in the medium to long term healing rates for the two procedures are very similar. There is currently scarce evidence for a sound decision making process among alternative treatments for the re-treatment of a periradicular pathosis. More well-designed RCTs should be performed with follow up of at least 4 years, and with a consistent sample size, to detect a true difference in the long term between the outcomes of the two alternative treatments, if any exist.

Results of endodontic retreatment: a randomized clinical study comparing surgical and nonsurgical procedures.

Information of "success" rates after surgical or nonsurgical endodontic retreatment is abundant but inconclusive. Reported healing frequencies vary between 45% and 90%. The present study was designed to find any systematic difference between the methods. Nonsurgical and surgical retreatment was randomly assigned to 95 endodontically "failed" cases. The outcome of the procedures was clinically and radiographically recorded, and followed for 4 years. At the 12-month recall, a statistically significant (p < 0.05) higher healing rate was observed for cases surgically retreated. At the final 48-month examination, no such difference was found. These findings may be explained by (a) slower healing dynamics in the nonsurgical group and (b) the event of late "failures" in the surgical group. Within the latter category, four cases classified as healed after 1 yr failed at the final follow-up. Conclusively, this study failed to show any systematic difference in the outcome of surgical and nonsurgical endodontic retreatment. Surgical retreatment seems to result in more rapid periapical bone fill, but also may imply a higher risk of "late failures." From a scientific point of view, the length of the follow-up period is very important and may strongly influence the conclusions made.

CD005511

The finding that healing rates can be higher for cases treated surgically as compared to those treated non-surgically, at least in the short term, is based on two RCTs only. A single RCT reported that in the medium to long term healing rates for the two procedures are very similar. There is currently scarce evidence for a sound decision making process among alternative treatments for the re-treatment of a periradicular pathosis. More well-designed RCTs should be performed with follow up of at least 4 years, and with a consistent sample size, to detect a true difference in the long term between the outcomes of the two alternative treatments, if any exist.

Postoperative discomfort associated with surgical and nonsurgical endodontic retreatment.

Endodontic retreatment decision-making must include an appraisal of the costs of the different strategies proposed. In addition to direct costs, postoperative discomfort may have other consequences in terms of time off work, unscheduled visits and suffering. To establish a foundation for the appraisal of such indirect and intangible costs the present study was set up in which patients' assessments of pain and swelling after surgical and nonsurgical retreatment procedures were recorded. Ninety-two patients with 95 root-filled incisors and canine teeth exhibiting apical periodontitis were included in the study. The mode of retreatment was randomly assigned. Each day during the first post-treatment week patients assessed their degree of swelling and pain on horizontal 100-mm visual analog scales (VAS). The scales ranged from "no swelling" to "very severe swelling" and "no pain" to "intolerable pain", respectively. Consumption of self-prescribed analgesics and time off work were also recorded. Significantly more patients reported discomfort after surgical retreatment than after nonsurgical procedures. High pain scores were most frequent on the operative day while swelling reached its maximum on the first postoperative day followed by progressive decrease both in frequency and magnitude. Postoperative symptoms associated with nonsurgical retreatment were less frequent but reached high VAS values in single cases. Analgesics were significantly more often consumed after periapical surgery. Patients reported absence from work mainly due to swelling and discoloration of the skin. This was found to occur only after surgical retreatment. Conclusively, surgical retreatment resulted in more discomfort and tended to bring about greater indirect costs than nonsurgical retreatment.

CD005511

The finding that healing rates can be higher for cases treated surgically as compared to those treated non-surgically, at least in the short term, is based on two RCTs only. A single RCT reported that in the medium to long term healing rates for the two procedures are very similar. There is currently scarce evidence for a sound decision making process among alternative treatments for the re-treatment of a periradicular pathosis. More well-designed RCTs should be performed with follow up of at least 4 years, and with a consistent sample size, to detect a true difference in the long term between the outcomes of the two alternative treatments, if any exist.

Clinical management of nonhealing periradicular pathosis. Surgery versus endodontic retreatment.

This prospective randomized study compared the outcome of retreatment and surgical intervention in root canal treated teeth with nonhealing periradicular pathosis. One such tooth from each of 38 patients was randomly allotted to retreatment or root-end resection and root-end filling. Treatment outcome after 1 year was evaluated and compared clinically and radiographically. The success rate for surgery was higher than for conventional retreatment, but the difference was not statistically significant. For management of nonhealing periradicular pathosis associated with root canal treated teeth, surgical intervention should be considered as an alternative to retreatment. In cases with a similar prognosis for both modes of treatment, the choice should be governed by consideration of intrinsic and extrinsic factors.

CD006854

The included trial was a small-scaled study and there were serious limitations in the design and methodology (e.g. allocation concealment was unclear, blinding of outcome assessor(s) was not ensured, few quantitative outcome measures were used, and the results were not reported as planned). Therefore, the current evidence supporting the efficacy of EPG is not strong and there remains a need for high-quality randomised controlled trials to be undertaken in this area.

Role of visual feedback treatment for defective /s/ sounds in patients with cleft palate.

The role of visual feedback in the treatment of defective /s/ sounds in patients with cleft palate is described. Six patients with cleft palate who were similar in age, velopharyngeal function, and type of misarticulation were selected for this study. Treatment was provided using either visual feedback or no visual feedback. Visual feedback for tongue placement was provided by the Rion Electropalatograph (EPG). Visual feedback for frication was provided by a multi-function speech training aid (MFSTA). Improvement in /s/ sound production was assessed objectively using a method described previously (Michi et al., 1986). The results indicated that visual feedback for tongue placement and frication was especially useful in the treatment of defective /s/ sounds in patients with cleft palate who exhibited abnormal posterior tongue posturing during the production of dental or alveolar sounds.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Evaluation of a child abuse prevention curriculum for third-grade students: assessment of knowledge and efficacy expectations.

Researchers investigated the effects of a child abuse prevention program on third-grade students' knowledge of child abuse and efficacy expectations regarding abusive situations. Three hundred forty-one students completed the 26-item pretest and posttest questionnaires (n = 166 for the intervention group, n = 175 for the control group). Results indicated a statistically significant increase in child abuse knowledge from pretest to posttest with the intervention group, with no change in knowledge for the control group. However, no significant increases occurred in efficacy expectations regarding abusive situations from pretest to posttest for either the intervention or control groups. Results from this study can be used to improve child abuse prevention programs through addressing program components that may affect factors other than student knowledge of abuse.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Child sexual abuse prevention programs: evaluating Who Do You Tell.

The research evaluated a sexual abuse prevention program for elementary school-aged children. Although other evaluations of similar programs have demonstrated significant improvements in knowledge and skills, a number of key questions with respect to their efficacy remain. 231 children were randomly assigned (matched by age) to participate in the program (N = 117) or in a wait-list control condition (N = 114). Knowledge of abuse prevention concepts were tested using the 33-item Children's Knowledge of Abuse Questionnaire-Revised (CKAQ-R), a standardized measure with strong psychometric properties (Tutty, 1995), with a new subscale on Appropriate Touch. An analysis of covariance showed that children who received the program increased their knowledge levels of both Inappropriate Touch (p = .000) and Appropriate Touch (p = .012) to a significantly greater degree than children in the control group. Age also significantly differentiated the knowledge levels regarding Inappropriate Touch, with younger children knowing fewer concepts both at pretest and posttest (p = .000). Parallel results apply to the Appropriate Touch subscale (p = .04). The results are consistent with other evaluations of child sexual abuse prevention programs, however the statistically significant though small gains suggest that the programs need to be presented in a more powerful manner.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Teaching personal safety skills for potential prevention of sexual abuse: a comparison of treatments.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Proximate effects of a child sexual abuse prevention program in elementary school children.

The effects of the sexual child abuse prevention program ESPACE were evaluated by means of a Solomon-type design with first and third grade children. ESPACE is an adaptation of the American Child Assault Prevention Program (CAP). Possible side effects of the program were also examined. A total of 133 children (64 first-graders and 69 third-graders) participated in the study. Children completed a knowledge questionnaire and a video vignette measure designed to evaluate preventive skills towards abusive and potentially abusive situations. A follow-up measure (2 months) was administered to verify whether knowledge and skills were maintained. Results indicated that children participating in the prevention program showed greater preventive knowledge and skills relative to children not participating. Follow-up data showed that knowledge gains were maintained while the preventive skill gains may attenuate. However, while global skill scores decreased between post-test and follow-up, children still showed greater preventive skills at follow-up than before the program. In terms of unanticipated side effects, results revealed that almost half of the parents noted positive reactions following children's participation in the ESPACE program. Furthermore, the majority of parents did not identify negative reactions in their children following their participation in the workshop. The findings suggest that the Quebec adaptation of the CAP program was effective in training children in abuse prevention concepts and skills.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Evaluating a prevention program for teenagers on sexual coercion: a differential effectiveness approach.

The authors evaluated a coeducational program for teenagers on preventing sexual coercion in dating situations. Students examined individual and social attitudes underlying coercive sexual behavior and learned communication skills aimed at preventing or dealing with unwanted sexual advances. Instruction was enhanced by video and an interactive video "virtual date." Outcomes were assessed using sexual attitude scales with a sample of 458 high school students. Student health education classes were randomly assigned to either a treatment or a control condition. Findings, based on a latent variable model of differential effectiveness, showed that students in the treatment group with initial coercive attitude scores at or above the mean benefited significantly more than students with the same range of scores in the control group.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Evaluation of a brief intervention for educating school children in awareness of physical and sexual abuse.

The development and evaluation of procedures for imparting information to children regarding inappropriate treatment by adults is a challenging task that warrants increased methodological sophistication. The present study was conducted to evaluate proximal changes in fourth and fifth graders' knowledge and attitudes of physical and sexual abuse following brief skits and focal discussion in the classroom. The study used a control group of children that did not receive the intervention, which permitted a more accurate understanding of the program's effectiveness. Relative to controls, children who received the program showed an overall increase in knowledge of correct actions to take in the event of potential or actual abuse. Limitations of the study, as well as suggestions for broadening the scope and impact of child abuse prevention programs for children are discussed in relation to these findings.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Teaching self-protection to children using television techniques.

This study compared the effectiveness of a videotape training program with other methods of teaching children self-protection to prevent child abduction. Subjects were kindergarten and first-grade students. Four experimental conditions were presented: videotape with behavior rehearsal, videotape only, a standard safety program, and no training. Acquisition of self-protective behaviors was measured at posttraining and follow-up by having confederate adults entice the children near their schools and homes. Results revealed that the videotape program with behavior rehearsal was highly effective in teaching children safe responses to potential abductors. The standard safety program was effective with fewer than half of the children. Three fourths of the children who received no training immediately agreed to go with the confederate suspects. The videotape program can be easily used with groups of young children in a classroom setting.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Evaluation of a sexual abuse prevention program for female Chinese adolescents with mild mental retardation.

The effectiveness of the Behavioral Skills Training program in the primary prevention of sexual abuse for 72 female Chinese adolescents with mild mental retardation was evaluated. Subjects were assigned to either the Behavior Skills Training program or an attention control program. The Behavioral Skills Training group demonstrated greater knowledge regarding sexual abuse and self-protection skills at posttest, which was maintained at 2-month follow-up, though the scores on the recognition of appropriate-touch requests showed a decreasing trend. They also exhibited less fear of objects, people, and situations after the prevention program. Booster sessions and a longer program duration should result in better retention. Results suggest that a modified Behavior Skill Training program can be effective with Chinese adolescents with mental retardation.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Evaluation of the effectiveness of Project Trust: an elementary school-based victimization prevention strategy.

This study employed a Posttest-Only Control Group Design to assess the effects of a victimization prevention program, Project TRUST, on elementary school students' knowledge of general prevention concepts, knowledge of difficult-to-acquire prevention concepts, anxiety, and reporting of abuse. A selected subgroup of experimental subjects was also assessed for retention of acquired concepts over time. Students exposed to Project TRUST demonstrated significantly greater knowledge of maltreatment prevention information, as well as difficult-to-acquire concepts, than control group students. A 3-month delayed reassessment of the experimental subgroup showed no loss in acquired prevention information. No differences in anxiety scores existed between experimental and control groups. First-time student abuse disclosures were greater in the experimental than in the control group. These findings support the effectiveness of Project TRUST as a strategy to increase prevention knowledge and generate abuse disclosures without creating student anxiety.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Child sexual abuse prevention: evaluation and one-year follow-up.

Because of the high incidence and negative psychological consequences of child sexual abuse, prevention programs have been developed and implemented nationwide. Few programs, however, have been comprehensively evaluated. In this multimodal study, a 3-session adaptation of the Feeling Yes, Feeling No curriculum was provided to 286 third and fourth graders from four schools whose responses were compared to 113 delayed-treatment control children from two schools. Program impact was assessed using a knowledge scale, the State-Trait Anxiety Inventory for Children, a videotape vignettes measure, a parent questionnaire, and disclosure data. Treatment children exhibited significantly greater knowledge and better ability to discriminate safe from unsafe situations on the video measure than control children at posttesting. These gains were maintained at 6-week follow-up testing. There were no differences in treatment and control children's self-reported anxiety or parents' reports of negative emotional/behavioral consequences, which were minimal. Over 5% of participating children reported ongoing or past sexual abuse. In the One-Year Follow-Up Study, children's knowledge gains and prevention skills scores on the video measure were maintained at one-year follow-up. A 1-session "booster shot" program further enhanced children's safety discrimination skills on the video measure.

CD004380

Studies evaluated in this review report significant improvements in knowledge measures and protective behaviours. Results might have differed had the true ICCs from studies been available or cluster-adjusted results been available. Several studies reported harms, suggesting a need to monitor the impact of similar interventions. Retention of knowledge should be measured beyond 3-12 months. Further investigation of the best forms of presentation and optimal age of programme delivery is required.

Educating children about sexual abuse: implications for pediatric intervention and possible prevention.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial.

Artemisinin-combination therapy (ACT) is recommended as first-line treatment of falciparum malaria throughout the world, and fixed-dose combinations are preferred by WHO; whether a single gametocytocidal dose of primaquine should be added is unknown. We aimed to compare effectiveness of four fixed-dose ACTs and a loose tablet combination of artesunate and mefloquine, and assess the addition of a single gametocytocidal dose of primaquine. In an open-label randomised trial in clinics in Rakhine state, Kachin state, and Shan state in Myanmar (Burma) between Dec 30, 2008, and March 20, 2009, we compared the effectiveness of all four WHO-recommended fixed-dose ACTs (artesunate-mefloquine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, artemether-lumefantrine) and loose artesunate-mefloquine in Burmese adults and children. Eligible patients were those who presented to the clinics with acute uncomplicated Plasmodium falciparum malaria or mixed infection, who were older than 6 months, and who weighed more than 5 kg. Treatments were randomised in equal numbers within blocks of 50 and allocation was in sealed envelopes. All patients were also randomly assigned to receive either a single dose of primaquine 0·75 mg base/kg or not. Patients were followed up for 63 days. Treatment groups were compared by analysis of variance and multiple logistic regression. The primary outcome was the 63 day recrudescence rate. This study is registered with clinicaltrials.gov, number NCT00902811. 155 patients received artesunate-amodiaquine, 162 artemether-lumefantrine, 169 artesunate-mefloquine, 161 loose artesunate-mefloquine, and 161 dihydroartemisinin-piperaquine. By day 63 of follow-up, 14 patients (9·4%; 95% CI 5·7-15·3%) on artesunate-amodiaquine had recrudescent P falciparum infections, a rate significantly higher than for artemether-lumefantrine (two patients; 1·4%; 0·3-5·3; p=0·0013), fixed-dose artesunate-mefloquine (0 patients; 0-2·3; p<0·0001), loose artesunate-mefloquine (two patients; 1·3%; 0·3-5·3; p=0·0018), and dihydroartemisinin-piperaquine (two patients 1·3%; 0·3-5·2%; p=0·0012). Hazard ratios for re-infection (95% CI) after artesunate-amodiaquine were 3·2 (1·3-8·0) compared with the two artesunate-mefloquine groups (p=0·01), 2·6 (1·0-6-0) compared with artemether-lumefantrine (p=0·04), and 2·3 (0·9-6·0) compared with dihydroartemisinin-piperaquine (p=0·08). Mixed falciparum and vivax infections were common: 129 (16%) had a mixed infection at presentation and 330 (41%) patients had one or more episodes of Plasmodium vivax infection during follow-up. The addition of a single dose of primaquine (0·75 mg/kg) reduced P falciparum gametocyte carriage substantially: rate ratio 11·9 (95% CI 7·4-20·5). All regimens were well tolerated. Adverse events were reported by 599 patients, most commonly vomiting and dizziness. Other side-effects were less common and were not related to a specific treatment. Artesunate-amodiaquine should not be used in Myanmar, because the other ACTs are substantially more effective. Artesunate-mefloquine provided the greatest post-treatment suppression of malaria. Adding a single dose of primaquine would substantially reduce transmission potential. Vivax malaria, not recurrent falciparum malaria, is the main complication after treatment of P falciparum infections in this region. Médecins sans Frontières (Holland) and the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme. Copyright © 2010 Elsevier Ltd. All rights reserved.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

A prospective study evaluating the efficacy of a single, 45-mg dose of primaquine, as a gametocytocidal agent, in patients with Plasmodium falciparum malaria in Mumbai, India.

The efficacy of a single dose of 45 mg primaquine, as a gametocytocidal agent, was assessed in Mumbai, India, among adults with uncomplicated or severe Plasmodium falciparum malaria. All the patients investigated had been found gametocytaemic, with at least 56 gametocytes/microl blood, within the first 72 h of their illness. Those with uncomplicated malaria, like those with severe malaria, were randomized to receive or not receive primaquine. All the patients were followed up for 29 days post-admission, for gametocytaemia and gametocyte viability (as determined by exflagellation). Among those with uncomplicated malaria, six (27.3%) of the 22 who did not receive primaquine but only one (4.2%) of the 24 who did receive the drug, on day 4, remained gametocytaemic on day 29 (P < 0.05). Similarly, seven (31.8%) of the 22 severe cases who did not receive primaquine but only two (9.5%) of the 21 severe cases who received the drug, on day 8, were found gametocytaemic on day 15 (P < 0.05). While the single, 45-mg dose of primaquine recommended by the World Health Organization was effective in clearing gametocytes from the blood of > 90% of the present cases of malaria, > 4% of the patients with uncomplicated malaria and > 9% of those with the severe disease continued to harbour gametocytes in their peripheral blood 29 and 15 days after taking the primaquine, respectively. Copyright 2004 The Liverpool School of Tropical Medicine

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

Defining Plasmodium falciparum treatment in South West Asia: a randomized trial comparing artesunate or primaquine combined with chloroquine or SP.

Antimalarial resistance has led to a global policy of artemisinin-based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia. The relative effect of artesunate (AS) or primaquine, as partner drugs, on clinical outcomes and gametocyte carriage in this setting were unknown. A single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+(single-dose)PQ; CQ+(3 d)AS; SP; SP+(single-dose)PQ, and SP+(3 d)AS. The objectives were to compare treatment failure rates and effect on gametocyte carriage, of CQ or SP monotherapy against the respective combinations (PQ or AS). Outcomes included trophozoite and gametocyte clearance (read by light microscopy), and clinical and parasitological failure. A total of 308 (87%) patients completed the trial. Failure rates by day 28 were: CQ 55/68 (81%); CQ+AS 19/67 (28%), SP 4/41 (9.8%), SP+AS 1/41 (2.4%). The addition of PQ to CQ or SP did not affect failure rates (CQ+PQ 49/67 (73%) failed; SP+PQ 5/33 (16%) failed). AS was superior to PQ at clearing gametocytes; gametocytes were seen on d7 in 85% of CQ, 40% of CQ+PQ, 21% of CQ+AS, 91% of SP, 76% of SP+PQ and 23% of SP+AS treated patients. PQ was more effective at clearing older gametocyte infections whereas AS was more effective at preventing emergence of mature gametocytes, except in cases that recrudesced. CQ is no longer appropriate by itself or in combination. These findings influenced the replacement of CQ with SP+AS for first-line treatment of uncomplicated falciparum malaria in the WHO Eastern Mediterranean Region. The threat of SP resistance remains as SP monotherapy is still common. Three day AS was superior to single-dose PQ for reducing gametocyte carriage. ClinicalTrials.gov NCT00959517.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

[Therapeutic efficacy of a regimen of artesunate-mefloquine-primaquine treatment for Plasmodium falciparum malaria and treatment effects on gametocytic development].

The treatment of Plasmodium falciparum malaria requires a safe and effective therapeutic treatment regimen, which in turn has high impact on the transmission. In 2006, an artesunate (AS)-mefloquine (MQ) treatment program was implemented in Antioquia. In addition, primaquine (PQ) was added to eliminate malaria gametocytes in the bloodstream. The efficacy and gametocytocidal activity was evaluated for two treatment regimens, AS-MQ-PQ and AS-MQ, in patients with uncomplicated P. falciparum malaria. Between April 2007 and February 2008, 50 patients were recruited for the trial in Turbo, Antioquia. A randomized clinical trial was conducted. Treatment compliance was supervised, with a clinical and parasitological assessment on days 1, 2, 3, 7, 14, 21, 28, 35, and 42 to evaluate response rate according to the WHO 2003 protocol. Clinical response and parasite elimination efficacy of AS-MQ (with or without PQ) was 100% (95% CI 86.3%-100%), and parasitemia and fever were absent on day 3 of treatment in all patients. Gametocyte elimination was superior when PQ was used--92% (95% CI: 74%-99%) of patients who received PQ had no gametocytes on day 3, compared to 78.3% (95% CI: 59%-93%) of patients who only received AS-MQ. Furthermore, circulating gametocytes were eliminated on average one week faster when the AS-MQ-PQ treatment scheme was used compared to the scheme without PQ. These studies recommend the use of AS-MQ to treat P. falciparum malaria given its good therapeutic efficacy. However, further assessment is suggested concerning the benefit of adding PQ to this treatment scheme.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

The treatment of malaria in glucose-6-phosphate dehydrogenase deficient patients in Sabah.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

The infectivity of gametocytes of Plasmodium falciparum from patients treated with artemisinin.

Twenty-seven patients with gametocytes of Plasmodium falciparum (PF) were divided into groups A, B, and C. A daily dose of 1200 mg artemisinin was given for 5 days to group A, a state dose of 750 mg of mefloquine to group B and a single dose of 750 mg mefloquine combined with 45 mg primaquine to group C. After treatment, the gametocyte count was taken daily, and infectivity of the gametocytes to Anopheles dirus via membrane feeding was also studied. Results showed that in group A, the density of gametocyte and infectivity were significantly reduced on days 4, 7, 14 and 21 after treatment; In group B, the gametocytes were significantly reduced on days 7, 14 and 21 and infectivity was significantly cut down on days 14 and 21 after medication. In group C, gametocytes disappeared in 5 out of 9 patients with failure of infecting mosquitoes in all 9 patients on day 4 after treatment. These indicate that artemisinin can effectively influence the infectivity of gametocytes of PF. Artemisinin is much better in blocking the transmission of PF malaria than mefloquine.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

A randomized open-label trial of artesunate- sulfadoxine-pyrimethamine with or without primaquine for elimination of sub-microscopic P. falciparum parasitaemia and gametocyte carriage in eastern Sudan.

In areas of seasonal malaria transmission, treatment of asymptomatic carriers of malaria parasites, whose parasitaemia persists at low densities throughout the dry season, could be a useful strategy for malaria control. We carried out a randomized trial to compare two drug regimens for clearance of parasitaemia in order to identify the optimum regimen for use in mass drug administration in the dry season. A two-arm open-label randomized controlled trial was conducted during the dry season in an area of distinct seasonal malaria in two villages in Gedarif State in eastern Sudan. Participants were asymptomatic adults and children aged over 6 months, with low-density P. falciparum infection detected by PCR. Participants were randomized to receive artesunate/sulfadoxine-pyrimethamine (AS+SP) combination for three days with or without a dose of primaquine (PQ) on the fourth day. Parasitaemia detected by PCR on days 3, 7 and 14 after the start of treatment and gametocytes detected by RT-PCR on days 7 and 14 were then recorded. 104 individuals who had low density parasitaemia at screening were randomized and treated during the dry season. On day 7, 8.3% were positive by PCR in the AS+SP+PQ group and 6.5% in the AS+SP group (risk difference 1.8%, 95%CI -10.3% to +13.8%). At enrolment, 12% (12/100) were carrying gametocytes. This was reduced to 6.4% and 4.4% by day 14 (Risk difference 1.9% (95%CI -9.3% to +13.2%) in AS+SP+PQ and AS+SP groups, respectively. Addition of primaquine to artemisinin combination treatment did not improve elimination of parasitaemia and prevention of gametocyte carriage in carriers with low-density parasitaemia in the dry season. ClinicalTrials.gov NCT00330902.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

Pharmacokinetic study of mefloquine in Thai children aged 5-12 years suffering from uncomplicated falciparum malaria treated with MSP or MSP plus primaquine.

A triple combination of mefloquine, sulfadoxine and pyrimethamine (MSP) was used with primaquine for the radical treatment of falciparum malaria in Thailand. Primaquine was reported to inhibit hepatic microsomal enzymes and drug metabolism in animal and man. 23 children hospitalized in the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Bangkok, Thailand, were randomly allocated into two groups, group I received MSP equivalent to 20 mg base of mefloquine/kg body weight and group II received MSP plus primaquine (0.75 mg/kg). No statistical difference was noted for clinical response except the gametocyte clearance time was shorter in children given MSP plus primaquine (7 +/- 2.7 days) than the children given MSP alone (21.9 +/- 4.4 days) (P < 0.01). No serious side effects were recorded in this study. The plasma samples were obtained for kinetic calculations by HPLC in 18 children (11 in group I, 7 in group II). Mean Cmax was 7.4 +/- 5.2 h in group I and 6.6 +/- 7.0 h in group II. Mean t1/2, Cl/f and Vd/f were 9.8 +/- 1.6 days, 0.43 +/- 0.16 ml/min/kg and 8.84 +/- 4.21 l/kg in group I, 9.3 +/- 1.4 days, 0.41 +/- 0.12 ml/min/kg and 8.91 +/- 3.00 l/kg group II, respectively. The comparison of kinetic parameters in groups I and II revealed no significant difference (P > 0.05) suggesting no drug interaction. These kinetic values in children given MSP suspension were considerably different to those in adult patients with shorter tmax, t1/2 and MRT. The coadministration of MSP and primaquine in children would benefit by reducing the transmission of malaria in endemic areas.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

Combined chloroquine, sulfadoxine/pyrimethamine and primaquine against Plasmodium falciparum in Central Java, Indonesia.

Chloroquine (CQ) or sulfadoxine-pyrimethamine (SP) monotherapy for Plasmodium falciparum often leads to therapeutic failure in Indonesia. Combining CQ with other drugs, like SP, may provide an affordable, available and effective option where artemisinin-combined therapies (ACT) are not licensed or are unavailable. This study compared CQ (n = 29 subjects) versus CQ + SP (with or without primaquine; n = 88) for clinical and parasitological cure of uncomplicated falciparum malaria in the Menoreh Hills region of southern Central Java, Indonesia. Gametocyte clearance rates were measured with (n = 56 subjects) and without (n = 61) a single 45 mg dose of primaquine (PQ). After 28 days, 58% of subjects receiving CQ had cleared parasitaemia and remained aparasitaemic, compared to 94% receiving CQ combined with SP (p < 0.001). Msp-2 genotyping permitted reinfection-adjusted cure rates for CQ and CQ combined with SP, 70% and 99%, respectively (p = 0.0006). Primaquine exerted no apparent affect on cure of asexual stage parasitaemia, but clearly accelerated clearance of gametocytes. CQ combined with SP was safe and well-tolerated with superior efficacy over CQ for P. falciparum parasitaemia in this study.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

Activities of artesunate and primaquine against asexual- and sexual-stage parasites in falciparum malaria.

The activities of primaquine in combination with quinine or artesunate against asexual- and sexual-stage parasites were assessed in 176 adult Thai patients with uncomplicated Plasmodium falciparum malaria. Patients were randomized to one of the six following 7-day oral treatment regimens: (i) quinine alone, (ii) quinine with tetracycline, (iii) quinine with primaquine at 15 mg/day, (iv) quinine with primaquine at 30 mg/day, (v) artesunate alone, or (vi) artesunate with primaquine. Clinical recovery occurred in all patients. There were no significant differences in fever clearance times, rates of P. falciparum reappearance, or recurrent vivax malaria between the six treatment groups. Patients treated with artesunate alone or in combination with primaquine had significantly shorter parasite clearance times (mean +/- standard deviation = 65 +/- 18 versus 79 +/- 21 h) and lower gametocyte carriage rates (40 versus 62.7%) than those treated with quinine (P < or = 0.007). Primaquine did not affect the therapeutic response (P > 0.2). Gametocytemia was detected in 98 patients (56% [22% before treatment and 34% after treatment]). Artesunate reduced the appearance of gametocytemia (relative risk [95% confidence interval] = 0.34 [0.17 to 0.70]), whereas combinations containing primaquine resulted in shorter gametocyte clearance times (medians of 66 versus 271 h for quinine groups and 73 versus 137 h for artesunate groups; P < or = 0.038). These results suggest that artesunate predominantly inhibits gametocyte development whereas primaquine accelerates gametocyte clearance in P. falciparum malaria.

CD008152

We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate.

P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) and contribute considerably to malaria transmission. We determined the efficacy of SP+AS plus a single dose of primaquine (PQ, 0.75 mg/kg) on clearing gametocytaemia measured by molecular methods. The study was conducted in Mnyuzi, an area of hyperendemic malaria in north-eastern Tanzania. Children aged 3-15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500-100,000 parasites/microL were randomized to receive treatment with either SP+AS or SP+AS+PQ. P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification (QT-NASBA). Haemoglobin levels (Hb) were determined to address concerns about haemolysis in G6PD-deficient individuals. 108 individuals were randomized. Pfs25 QT-NASBA gametocyte prevalence was 88-91% at enrolment and decreased afterwards for both treatment arms. Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ. On day 14 after treatment 3.9% (2/51) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7% (32/51) of those treated with SP+AS (p<0.001). Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency. The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment. PQ clears submicroscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission. For individuals without severe anaemia, addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment. Controlled-Trials.com ISRCTN61534963.

CD004455

The data were too few and of insufficient quality to make any recommendations for practice. Future research on antibiotic prophylaxis for operative vaginal delivery is needed to conclude whether it is useful for reducing postpartum morbidity.

Efficacy of prophylactic antibiotics for the prevention of endomyometritis after forceps delivery.

The purpose of this prospective randomized controlled clinical trial was to determine whether prophylactic antibiotics reduce the incidence of endomyometritis after forceps delivery. Of the 393 patients studied, 192 received 2 gm of intravenous cefotetan after forceps delivery, and 201 patients received no antibiotics. There were seven cases of endomyometritis in the group given no antibiotic and none in the cefotetan group, a statistically significant difference (P less than .01). We conclude that prophylactic antibiotics are effective in reducing the incidence of endomyometritis after forceps delivery. We believe this is the first published study demonstrating this benefit.

CD004012

The data from five trials comparing differing washout policies were sparse and trials were generally of poor quality or poorly reported. The evidence was too scanty to conclude whether or not washouts were beneficial. In the first instance we require further rigorous, high quality trials with adequate power to detect any benefit from washout being performed as opposed to none. Then trials comparing different washout solutions, washout volumes, frequencies/timings and routes of administration are needed.

Evaluation of 3 methods of bladder irrigation to treat bacteriuria in persons with neurogenic bladder.

We conducted a randomized, double-blind comparison of twice daily bladder irrigation using 1 of 3 different solutions in community-residing persons with neurogenic bladder who used indwelling catheters to evaluate efficacy in treatment of bacteriuria. Eighty-nine persons with bacteriuria were randomized to irrigate their bladders twice daily for 8 weeks with 30 mL of (a) sterile saline, (b) acetic acid, or (c) neomycin-polymyxin solution. Urinalysis, cultures, and antimicrobial susceptibility tests were performed at baseline and weeks 2, 4, and 8 to determine the extent to which each of the solutions affected numbers and types of bacteria, urinary pH, urinary leukocytes, and generation of antimicrobial-resistant organisms. Bladder irrigation was well tolerated with the exception of 3 participants who had bladder spasms. None of the 3 irrigants had a detectable effect on the degree of bacteriuria or pyuria in 52 persons who completed the study protocol. A significant increase in urinary pH occurred in all 3 groups. No significant development of resistance to oral antimicrobials beyond what was observed at baseline was detected. Bladder irrigation was generally well tolerated for 8 weeks. No advantages were detected for neomycin-polymyxin or acetic acid over saline in terms of reducing the urinary bacterial load and inflammation. We cannot recommend bladder irrigation as a means of treatment for bacteriuria in persons with neurogenic bladder.

CD004012

The data from five trials comparing differing washout policies were sparse and trials were generally of poor quality or poorly reported. The evidence was too scanty to conclude whether or not washouts were beneficial. In the first instance we require further rigorous, high quality trials with adequate power to detect any benefit from washout being performed as opposed to none. Then trials comparing different washout solutions, washout volumes, frequencies/timings and routes of administration are needed.

Do catheter washouts extend patency time in long-term indwelling urethral catheters? A randomized controlled trial of acidic washout solution, normal saline washout, or standard care.

Blockage of long-term indwelling catheters with mineral deposit is an ongoing management issue, but evidence on optimal management is lacking. Our purpose was to examine whether catheter washouts prevent or reduce catheter blockage. A multisite randomized controlled trial. Adults with long-term indwelling catheters that required changing every 3 weeks or less, living in the community, and requiring supportive or continuing care were recruited. Participants were randomly assigned to 1 of 3 groups: control (usual care, no washout), saline washout, or commercially available acidic washout solution (Contisol Maelor Pharmaceuticals Ltd, Wrexham, UK). At baseline visit, the catheter was changed and participants were followed weekly for 8 weeks, with checks for catheter patency and urine pH. Participants randomized to saline or commercial solution had a weekly washout with the appropriate solution. Endpoints were 8 weeks (completion data), 3 or more catheter changes in the 8-week period, or symptomatic urinary tract infection (UTI) requiring antibiotics. The study hypothesis was that catheter life would be extended by 25% in the commercial solution group. It was not possible to blind participants or research nurses to washout versus no intervention, but participants in the saline and washout solution groups were blinded to solution type. One hundred twelve potential participants were screened; 73 were enrolled, randomized, and included in the final analysis. Of these, 53 completed the full 8 weeks of data collection; 16 terminated early because of 3 catheter changes or self-reported 'UTI'. Other reasons for termination were hematuria, latex sensitivity, deceased/severe illness, or personal choice. Analysis of variance was used to analyze mean differences on demographic variables and mean number of weeks in study. Kaplan-Meier survival curve analysis showed no statistical difference between the groups in time to first catheter change. At this time, the evidence is insufficient to state whether catheter washout with saline or Contisol is more effective than usual care with no washout in preventing blocking. No increased risk of UTI was associated with washout regimes.

CD004012

The data from five trials comparing differing washout policies were sparse and trials were generally of poor quality or poorly reported. The evidence was too scanty to conclude whether or not washouts were beneficial. In the first instance we require further rigorous, high quality trials with adequate power to detect any benefit from washout being performed as opposed to none. Then trials comparing different washout solutions, washout volumes, frequencies/timings and routes of administration are needed.

Once-daily irrigation of long-term urethral catheters with normal saline. Lack of benefit.

Urinary incontinence is often managed with a long-term urethral catheter after other methods have failed. Such urethral catheterization is associated with polymicrobial bacteriuria, catheter obstruction, fever, bacteremia, urinary tract stones, and death. Periodic catheter irrigation is a common but untested management procedure intended to prevent catheter obstruction, fevers, and/or bacteremia. To evaluate this technique, we performed a randomized crossover trial comparing ten weeks of once-daily normal saline irrigation with ten weeks of no irrigation in 32 long-term catheterized women. The incidence of catheter obstructions and febrile episodes and the prevalence and species of bacteriuria were similar whether examined as completed crossover patients (N = 23) or as partially completed trials (N = 9). Once-daily irrigation with normal saline of long-term urethral catheters is a time-consuming and costly procedure that is unlikely to have an impact on the morbidity associated with such catheters.

CD004012

The data from five trials comparing differing washout policies were sparse and trials were generally of poor quality or poorly reported. The evidence was too scanty to conclude whether or not washouts were beneficial. In the first instance we require further rigorous, high quality trials with adequate power to detect any benefit from washout being performed as opposed to none. Then trials comparing different washout solutions, washout volumes, frequencies/timings and routes of administration are needed.

Assessment of the use of bladder washouts/instillations in patients with long-term indwelling catheters.

A randomised cross-over study of 3 bladder washout treatments--saline, Suby G and Solution R--was conducted on 25 elderly females with long-term catheters in order to examine crystal formation and catheter encrustation. With 2 exceptions, all patients produced crystals; only 14 completed the study. While a significant reduction in struvite crystals was found in the returned acidic washout fluid, there was no significant reduction of crystals in the neutral (saline) washout following any of the 3-week periods of treatment. Uric acid crystals appeared with Suby G and Solution R and these solutions were associated with higher red cell deposits in the urine. There was no significant difference in catheter encrustation between the various washouts.

CD009058

On the basis of one randomised clinical trial with high risk of bias, there is insufficient evidence to conclude if in patients with liver metastases from various primary sites cryotherapy brings any significant benefit in terms of survival or recurrence compared with conventional surgery. In addition, there is no evidence for the effectiveness of cryotherapy when compared with no intervention. At present, cryotherapy cannot be recommended outside randomised clinical trials.

Hepatic cryosurgery for liver metastases. Long-term follow-up.

The aim of this prospective study was to evaluate the applicability of cryogenic and conventional surgery in treating liver metastases (LM) with respect to intraoperative tumor reduction and survival rate. As have been shown in animal experiments as well as in clinical investigations, cryosurgery has been used for the treatment of many benign and malignant conditions. For the first time, this report summarizes a 10-year follow-up clinical experience with cryosurgery for treatment of LM from 1983 to 1992. One hundred twenty-three patients with LM (87 males and 36 females, a ratio 2.4:1.0; age, 41.3 +/- 12.1 years) were stratified and entered into a long-term prospective, randomized clinical trial for cryogenic surgery in group 1 (n = 63) and conventional surgical techniques in group 2 (control subjects, n = 60). Principally, a self-constructed cryogenic clamp was used for hepatic cryoresection with preliminary freezing of the margin resection by a cryosurgical system "Cryoelectronic-2" or "Cryoelectronic-4". Hepatic cryoextirpation (cryoablation) and hepatic cryodestruction were performed by means of probes of different roughly disk design from phi 5 mm to 55 mm by volume of frozen zone of 40 cm3 to 180 cm3 for approximately 7 to 32 minutes. In most cases in group 1 and group 2, LM were based on colorectal cancers (65% vs. 68%). The hepatic cryosurgical procedures in group 1 included cryoextirpation (29 patients, 46%), cryoresection (20 patients, 32%), and cryodestruction (14 patients, 22%) solely. Clinical and laboratory parameters showed that the curative effects were significantly higher in group 1 than in group 2. The 3-year survival rate was in group 1 and group 2 (60% vs. 51%, respectively). The 5-year survival rate was 44% in group 1 and 36% in group 2. Twelve patients (19%) versus 5 patients (8%) in group 1 and group 2, respectively, survived 10 years. The disease-free survival was in group 1 and group 2 (30% vs. 18%, respectively). During a follow-up period, recurrence in the liver was observed in 54 patients (85%) in group 1 and in 57 patients (95%) in control subjects. After a 10-year follow-up period in group 1 and group 2, 9 patients (14%) versus 3 patients (5%) remained disease free, 3 patients (4%) versus 2 patients (3%) were surviving with disease, and 51 patients (81%) versus 55 patients (92%) died. The data of this 10-year prospective, randomized clinical trial suggest that hepatic cryosurgery is effective in the treatment of resectable and nonresectable LM. The results show intraoperative tumor reduction (> or = 90% < or = 97%) and extended higher survival in these patients. The study indicated a 5-year and 10-year survival rate of 44% and 19% after cryosurgery, respectively.

CD009217

Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved.

Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group.

To provide a firmer basis for preventing high blood pressure (BP), we tested interventions to promote weight loss, dietary sodium reduction, and their combination for lowering diastolic BP, systolic BP, and the incidence of hypertension during a 3- to 4-year period. We conducted a randomized, 2 x 2 factorial, clinical trial, with BP levels measured by blinded observers. Nine academic medical centers recruited 2382 men and women (age range, 30-54 years) not taking antihypertensive drugs, with a diastolic BP of 83 to 89 mm Hg, a systolic BP lower than 140 mm Hg, and a body mass index (the weight in kilograms divided by the square of the height in meters) representing 110% to 165% of desirable body weight. Counseling aimed at helping participants achieve their desirable weight or a 4.5-kg or more weight reduction (in the weight loss and combined groups) and/or sodium intake of 80 mmol/d (in the sodium reduction and combined groups) was provided. From baseline, participants' weight decreased by 4.3 to 4.5 kg at 6 months and by approximately 2 kg at 36 months in the weight loss and combined groups compared with weight changes in the usual care group (all groups, P < .001). Sodium excretion decreased 50 and 40 mmol/d at 6 and 36 months, respectively, in the sodium reduction group and about 15 mmol/d less at each time point in the combined group compared with the usual care group (all groups, P < .01). Compared with the usual care group, BP decreased 3.7/2.7 mm Hg in the weight loss group, 2.9/1.6 mm Hg in the sodium reduction group, and 4.0/2.8 mm Hg in the combined group at 6 months (all groups, P < .001). At 36 months, BP decreases remained greater in the active intervention groups than in the usual care group (weight loss group, 1.3/0.9 mm Hg; sodium reduction group, 1.2/0.7 mm Hg; combined group, 1.1/0.6 mm Hg). Differences were statistically significant for systolic and diastolic BP in the weight loss group and for systolic BP in the sodium reduction group. Through 48 months, the incidence of hypertension (BP > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic or the use of antihypertensive drugs) was significantly less in each active intervention group than the usual care group (average relative risks, 0.78-0.82). In overweight adults with high-normal BP, weight loss and reduction in sodium intake, individually and in combination, were effective in lowering systolic and diastolic BP, especially in the short-term (6 months). Although the effects on average BP declined over time, reductions in hypertension incidence were achieved.

CD009217

Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved.

Effect of potassium-enriched salt on cardiovascular mortality and medical expenses of elderly men.

The beneficial effects of potassium-enriched salt on blood pressure have been reported in a few short-term trials. The long-term effects of potassium-enriched salt on cardiovascular mortality have not been carefully studied. The objective was to examine the effects of potassium-enriched salt on cardiovascular disease (CVD) mortality and medical expenditures in elderly veterans. Five kitchens of a veteran retirement home were randomized into 2 groups (experimental or control) and veterans assigned to those kitchens were given either potassium-enriched salt (experimental group) or regular salt (control group) for approximately 31 mo. Information on death, health insurance claims, and dates that veterans moved in or out of the home was gathered. Altogether, 1981 veterans, 768 in the experimental [x (+/-SD) age: 74.8 +/- 7.1 y] and 1213 in the control (age: 74.9 +/- 6.7 y) groups, were included in the analysis. The experimental group had better CVD survivorship than did the control group. The incidence of CVD-related deaths was 13.1 per 1000 persons (27 deaths in 2057 person-years) and 20.5 per 1000 (66 deaths in 3218 person-years) for the experimental and control groups, respectively. A significant reduction in CVD mortality (age-adjusted hazard ratio: 0.59; 95% CI: 0.37, 0.95) was observed in the experimental group. Persons in the experimental group lived 0.3-0.90 y longer and spent significantly less (approximately US Dollars 426/y) in inpatient care for CVD than did the control group, after control for age and previous hospitalization expenditures. This study showed a long-term beneficial effect on CVD mortality and medical expenditure associated with a switch from regular salt to potassium-enriched salt in a group of elderly veterans. The effect was likely due to a major increase in potassium and a moderate reduction in sodium intakes.

CD009217

Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved.

Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group.

Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly, but there is a paucity of evidence from randomized controlled trials in support of this recommendation. To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension. Randomized controlled trial. A total of 975 [corrected] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication. Four academic health centers. The 585 obese participants were randomized to reduced sodium intake, weight loss, both, or usual care, and the 390 nonobese participants were randomized to reduced sodium intake or usual care. Withdrawal of antihypertensive medication was attempted after 3 months of intervention. Diagnosis of high blood pressure at 1 or more follow-up visits, or treatment with antihypertensive medication, or a cardiovascular event during follow-up (range, 15-36 months; median, 29 months). The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake (relative hazard ratio, 0.69; 95% confidence interval [CI], 0.59-0.81; P<.001) and, in obese participants, among those assigned vs not assigned to weight loss (relative hazard ratio, 0.70; 95% CI, 0.57-0.87; P<.001). Relative to usual care, hazard ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P<.001) for reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss alone, and 0.47 (95% CI, 0.35-0.64; P<.001) for reduced sodium intake and weight loss combined. The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups. Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons.

CD009217

Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved.

The Hypertension Prevention Trial: three-year effects of dietary changes on blood pressure. Hypertension Prevention Trial Research Group.

A total of 841 healthy men and women aged 25 to 49 years, with diastolic blood pressures of 78 to 89 mm Hg, were randomly assigned to a control treatment group (no dietary counseling) or to one of four dietary counseling treatment groups (reduced calories, reduced sodium, reduced sodium and calories, or reduced sodium and increased potassium). Participants were followed for a 3-year period to assess the effect of dietary changes on blood pressure. After 6 months, counseling had resulted in a net (of control) mean overnight urinary sodium reduction of 13%, a potassium increase of 8%, and a decrease in mean body weight of 7%. At 3 years, the sodium and weight reductions were 10% and 4%, respectively; the potassium change was nil. All four dietary counseling treatment groups had lower mean blood pressures than the control group. The largest net reduction in blood pressure occurred in the calorie group: diastolic pressure was 2.8 mm Hg and 1.8 mm Hg and systolic pressure, 5.1 mm Hg and 2.4 mm Hg at 6 months and 3 years, respectively. All four dietary counseling treatment groups experienced fewer hypertensive events; significantly fewer occurred in the sodium groups. The beneficial effects on blood pressure achieved in this trial have implications for the prevention of cardiovascular disease through dietary reduction of calories and sodium.

CD009217

Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved.

The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I.

To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure. Randomized control multicenter trials. Volunteers recruited from the community, treated and followed up at special clinics. Of 16,821 screenees, 2182 men and women, aged 30 through 54 years, with diastolic blood pressure from 80 through 89 mm Hg were selected. Of these, 50 did not return for follow-up blood pressure measurements. Three life-style change groups (weight reduction, sodium reduction, and stress management) were each compared with unmasked nonintervention controls over 18 months. Four nutritional supplement groups (calcium, magnesium, potassium, and fish oil) were each compared singly, in double-blind fashion, with placebo controls over 6 months. Primary: change in diastolic blood pressure from baseline to final follow-up, measured by blinded observers. Secondary: changes in systolic blood pressure and intervention compliance measures. Weight reduction intervention produced weight loss of 3.9 kg (P less than .01), diastolic blood pressure change of -2.3 mm Hg (P less than .01), and systolic blood pressure change of -2.9 mm Hg (P less than .01). Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h (P less than .01), diastolic blood pressure by 0.9 mm Hg (P less than .05), and systolic blood pressure by 1.7 mm Hg (P less than .01). Despite good compliance, neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly (P greater than .05). Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons. Sodium reduction is also effective. The long-term effects of weight reduction and sodium reduction, alone and in combination, require further evaluation.

CD002929

From the limited results it is unclear whether the wearing of surgical face masks by members of the surgical team has any impact on surgical wound infection rates for patients undergoing clean surgery.

Trial of the use of masks in the gynaecological operating theatre.

A randomly controlled trial was performed on 41 women having gynaecological surgery in which the team of surgeons and nurses wore or did not wear masks. After major abdominal surgery, 3 of 5 patients in the unmasked group developed wound infections whereas no infection was observed in the 4 patients of the masked group. A greater number of Streptococci were also found by settle-plates on the operating table in the unmasked group. No infection was recorded after minor or vaginal surgery.

CD002929

From the limited results it is unclear whether the wearing of surgical face masks by members of the surgical team has any impact on surgical wound infection rates for patients undergoing clean surgery.

Use of face masks by non-scrubbed operating room staff: a randomized controlled trial.

Ambiguity remains about the effectiveness of wearing surgical face masks. The purpose of this study was to assess the impact on surgical site infections (SSIs) when non-scrubbed operating room staff did not wear surgical face masks. Eight hundred twenty-seven participants undergoing elective or emergency obstetric, gynecological, general, orthopaedic, breast or urological surgery in an Australian tertiary hospital were enrolled. Complete follow-up data were available for 811 patients (98.1%). Operating room lists were randomly allocated to a 'Mask group' (all non-scrubbed staff wore a mask) or 'No Mask group' (none of the non-scrubbed staff wore masks). The primary end point, SSI was identified using in-patient surveillance; post discharge follow-up and chart reviews. The patient was followed for up to six weeks. Overall, 83 (10.2%) surgical site infections were recorded; 46/401 (11.5%) in the Masked group and 37/410 (9.0%) in the No Mask group; odds ratio (OR) 0.77 (95% confidence interval (CI) 0.49 to 1.21), p = 0.151. Independent risk factors for surgical site infection included: any pre-operative stay (adjusted odds ratio [aOR], 0.43 (95% CI, 0.20; 0.95), high BMI aOR, 0.38 (95% CI, 0.17; 0.87), and any previous surgical site infection aOR, 0.40 (95% CI, 0.17; 0.89). Surgical site infection rates did not increase when non-scrubbed operating room personnel did not wear a face mask.

CD002929

From the limited results it is unclear whether the wearing of surgical face masks by members of the surgical team has any impact on surgical wound infection rates for patients undergoing clean surgery.

Postoperative wound infections and surgical face masks: a controlled study.

It has never been shown that wearing surgical face masks decreases postoperative wound infections. On the contrary, a 50% decrease has been reported after omitting face masks. The present study was designed to reveal any 30% or greater difference in general surgery wound infection rates by using face masks or not. During 115 weeks, a total of 3,088 patients were included in the study. Weeks were denoted as "masked" or "unmasked" according to a random list. After 1,537 operations performed with face masks, 73 (4.7%) wound infections were recorded and, after 1,551 operations performed without face masks, 55 (3.5%) infections occurred. This difference was not statistically significant (p greater than 0.05) and the bacterial species cultured from the wound infections did not differ in any way, which would have supported the fact tha the numerical difference was a statistically "missed" difference. These results indicated that the use of face masks might be reconsidered. Masks may be used to protect the operating team from drops of infected blood and from airborne infections, but have not been proven to protect the patient operated by a healthy operating team.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.

Varenicline, a partial agonist at the alpha4beta2 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine. To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR). A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study. Varenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling. Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52). During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%). Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR. clinicaltrials.gov Identifier: NCT00143364.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Behavioral counseling and varenicline treatment for smoking cessation.

Smoking remains the primary preventable cause of death and illness in the U.S. Effective, convenient treatment programs are needed to reduce smoking prevalence. This study compared the effectiveness of three modalities of a behavioral smoking-cessation program in smokers using varenicline. Current treatment-seeking smokers (n=1202) were recruited from a large healthcare organization between October 2006 and October 2007. Eligible participants were randomized to one of three smoking-cessation interventions: web-based counseling (n=401); proactive telephone-based counseling (PTC; n=402); or combined PTC and web counseling (n=399). All participants received a standard 12-week FDA-approved course of varenicline. Self-report determined the primary outcomes (7-day point prevalent abstinence at 3- and 6-month follow-ups); the number of days varenicline was taken; and treatment-related symptoms. Behavioral measures determined utilization of both the web- and Phone-based counseling. Intent-to-treat analyses revealed relatively high percentages of abstinence at 3 months (38.9%, 48.5%, 43.4%) and at 6 months (30.7%, 34.3%, 33.8%) for the web, PTC, and PTC-web groups, respectively. The PTC group had a significantly higher percentage of abstinence than the web group at 3 months (OR=1.48, 95% CI=1.12, 1.96), but no between-group differences in abstinence outcomes were seen at 6 months. Phone counseling had greater treatment advantage for early cessation and appeared to increase medication adherence, but the absence of differences at 6 months suggests that any of the interventions hold promise when used in conjunction with varenicline. 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation.

The selective nicotinic acetylcholine receptor partial agonist, varenicline tartrate, represents a novel type of therapy for smoking cessation. This study evaluated the efficacy, safety, and tolerability of 4 varenicline dose regimens, 2 with progressive dosing over the first week (eg, titrated) and 2 with a fixed dosing schedule (eg, non-titrated), for promoting smoking cessation. This multicenter, double-blind, placebo-controlled study randomized healthy smokers (aged 18-65 years) to varenicline tartrate, 0.5 mg twice daily nontitrated (n = 129), 0.5 mg twice daily titrated (n = 130), 1.0 mg twice daily nontitrated (n = 129), 1.0 mg twice daily titrated (n = 130), or placebo (n = 129) for 12 weeks to aid in smoking cessation. A 40-week follow-up period assessed long-term efficacy. The primary efficacy measures were the carbon monoxide-confirmed 4-week continuous quit rates by pooled dosage group for weeks 4 through 7 and 9 through 12 and the continuous abstinence rates for weeks 9 through 52. Weeks 9 through 12 continuous quit rates were greater in the 1.0-mg group (49.4%) and the 0.5-mg group (44.0%) vs placebo (11.6%; P<.001 vs both doses). Weeks 9 through 52 abstinence rates were greater in the 1.0-mg group (22.4%; P<.001) and the 0.5-mg group (18.5%; P<.001) vs placebo (3.9%). Varenicline was generally well tolerated, with nausea occurring in 16% to 42% of varenicline-treated subjects. Reports of nausea were lower for the titrated vs nontitrated dosing and infrequently led to medication discontinuation. Varenicline tartrate, 0.5 mg and 1.0 mg twice daily, is efficacious for smoking cessation.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Dianicline, a novel α4β2 nicotinic acetylcholine receptor partial agonist, for smoking cessation: a randomized placebo-controlled clinical trial.

Dianicline is a α4β2 nicotinic acetylcholine receptor partial agonist, a class of drugs that includes varenicline and cytisine. Varenicline is efficacious for smoking cessation, while cytisine has not been studied systematically. The efficacy of dianicline has not been previously tested in an adequately powered study. In a randomized, double-blind, parallel group placebo-controlled trial, 602 generally healthy cigarette smokers were assigned to dianicline (n = 300) or placebo (n = 302) for 7 weeks followed by a 19-week off drug follow-up period. Exhaled carbon monoxide and cotinine-confirmed continuous abstinence rates for Weeks 4-7 were 24.0% for dianicline versus 20.5% for placebo (odds ratio 1.22; 95% CI, 0.83-1.80; p = .307). For Weeks 4-26, the abstinence rates were 16.7% for dianicline versus 13.9% for placebo (odds ratio 1.24; 95% CI, 0.79-1.93; p = .366). Craving for a cigarettes was reduced by dianicline compared with placebo after 7 weeks (p = .0175). Nicotine withdrawal symptoms measured by the Hughes and Hatsukami Minnesota Withdrawal Scale were lower for dianicline compared with placebo in the first 3 weeks of treatment during which time quit rates were also higher in the dianicline-treated group. Dianicline did not increase cigarette smoking abstinence rates beyond the initial phase of treatment. However, self-reported craving and nicotine withdrawal symptoms were reduced.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Placebo-controlled trial of cytisine for smoking cessation.

Cytisine, a partial agonist that binds with high affinity to the α(4)β(2) nicotinic acetylcholine receptor, is a low-cost treatment that may be effective in aiding smoking cessation. This study assessed the efficacy and safety of cytisine as compared with placebo. We conducted a single-center, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive cytisine or matching placebo for 25 days; participants in both groups received a minimal amount of counseling during the study. The primary outcome measure was sustained, biochemically verified smoking abstinence for 12 months after the end of treatment. Of 1542 adult smokers screened, 740 were enrolled and 370 were randomly assigned to each study group. The rate of sustained 12-month abstinence was 8.4% (31 participants) in the cytisine group as compared with 2.4% (9 participants) in the placebo group (difference, 6.0 percentage points; 95% confidence interval [CI], 2.7 to 9.2; P=0.001). The 7-day point prevalence for abstinence at the 12-month follow-up was 13.2% in the cytisine group versus 7.3% in the placebo group (P=0.01). Gastrointestinal adverse events were reported more frequently in the cytisine group (difference, 5.7 percentage points; 95% CI, 1.2 to 10.2). In this single-center study, cytisine was more effective than placebo for smoking cessation. The lower price of cytisine as compared with that of other pharmacotherapies for smoking cessation may make it an affordable treatment to advance smoking cessation globally.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Effects of varenicline in adult smokers: a multinational, 24-week, randomized, double-blind, placebo-controlled study.

Prevalence rates of smoking are rising in developing countries. Previous trials evaluating the efficacy and tolerability of the smoking-cessation medication varenicline have used largely participants of Caucasian origin. This study was conducted to evaluate the efficacy and tolerability of varenicline in populations of participants from Latin America, Africa, and the Middle East to investigate potential differences in the therapeutic response to varenicline. This multinational, randomized, double-blind, placebo-controlled trial was conducted at 42 centers in 11 countries (Latin America: Brazil, Colombia, Costa Rica, Mexico, and Venezuela; Africa: Egypt and South Africa; Middle East: Jordan, Lebanon, Saudi Arabia, and the United Arab Emirates). Participants were male and female smokers aged 18 to 75 years who were motivated to stop smoking; smoked ≥10 cigarettes/d, with no cumulative period of abstinence >3 months in the previous year; and who had no serious or unstable disease within the previous 6 months. Subjects were randomized in a 2:1 ratio to receive varenicline 1 mg or placebo, BID for 12 weeks, with a 12-week nontreatment follow-up. Brief smoking-cessation counseling was provided. The main outcome measures were carbon monoxide-confirmed continuous abstinence rate (CAR) at weeks 9 to 12 and weeks 9 to 24. Adverse events (AEs) were recorded for tolerability assessment. Overall, 588 subjects (varenicline, 390; placebo, 198) were randomized and treated. The mean (SD) ages of subjects in the varenicline and placebo groups were 43.1 (10.8) and 43.9 (10.8) years, respectively; 57.7% and 65.7% were male; and the mean (SD) weights were 75.0 (16.0) and 76.7 (16.3) kg (range, 40.0-130.0 and 45.6-126.0 kg). CAR at weeks 9 to 12 was significantly higher with varenicline than with placebo (53.59% vs 18.69%; odds ratio [OR] = 5.76; 95% CI, 3.74-8.88; P < 0.0001), and this rate was maintained during weeks 9 to 24 (39.74% vs 13.13%; OR = 4.78; 95% CI, 2.97-7.68; P < 0.0001). Nausea, headache, and insomnia were the most commonly reported AEs with varenicline and were reported numerically more frequently in the varenicline group compared with the placebo group. Serious AEs (SAEs) were reported in 2.8% of varenicline recipients compared with 1.0% in the placebo group, with 6 subjects reporting psychiatric SAEs compared with none in the placebo group. Based on these data, varenicline was apparently efficacious and generally well tolerated as a smoking-cessation aid in smokers from selected sites in Latin America, Africa, and the Middle East. ClinicalTrials.gov identifier: NCT00594204. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up.

Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control. A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks. During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline. Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers.

Varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, has been developed specifically for smoking cessation. In Japan, 39.3% of men smoke and this is a major public health concern. The primary objective of this study was to evaluate the efficacy and dose-response relationship of varenicline in Japanese smokers. In this double-blind, placebo-controlled, randomized, parallel-group study, subjects were randomized to receive varenicline at 0.25 mg BID, 0.5 mg BID, 1 mg BID, or placebo for 12 weeks followed by a 40-week, nontreatment follow-up phase. The primary efficacy variable was the continuous abstinence rate (CAR), defined as no reported smoking (not even a puff) or other nicotine use and confirmed by end-expiratory carbon monoxide level <or=10 ppm, during the last 4 weeks of treatment (weeks 9-12). Secondary end points included CARs for weeks 9-24 and 9-52. Craving, withdrawal, and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal Scale, the Brief Questionnaire on Smoking Urges, and the modified Cigarette Evaluation Questionnaire. The tolerability of varenicline was also evaluated. Of 618 subjects who received treatment, 515 (83.3%) were classified as nicotine dependent (scoring >or=5 on the Tobacco Dependence Screener), and constituted the primary analysis group. Of these, 385 (74.8%) subjects were male, and the mean age was within the range of 39.0 to 40.2 years. Across treatment groups, subjects claimed to have smoked a mean of 23.1 to 24.9 cigarettes per day in the preceding 30 days, and the mean score on the Fagerström Test for Nicotine Dependence was within the range from 5.4 to 5.7. The CAR for weeks 9-12 was significantly higher for all doses of varenicline compared with placebo (39.5% [51/129]). The highest CAR of 65.4% (85/130) was achieved with varenicline 1 mg BID (odds ratio [OR] [95% CI] = 2.98 [1.78-4.99]; P < 0.001). The CAR for weeks 9-52 was significantly greater for varenicline 1 mg BID than placebo (34.6% [45/130] vs 23.3% [30/129]; OR [95% CI] = 1.81 [1.04-3.17]; P = 0.036). The CARs for weeks 9-24 at 0.25, 0.5, and 1 mg BID were 33.6% (43/128), 35.2% (45/128), 37.7% (49/130), and for weeks 9-52 at 0.25 and 0.5 mg BID were 27.3% (35/128) and 28.9% (37/128) but failed to reach significance versus the placebo (29.5% [38/129] for weeks 9-24 and 23.3% [30/129] for weeks 9-52). Treatment-emergent adverse events (AEs) were more prevalent among varenicline-treated subjects (79.1% [121/153] at 0.25 mg BID, 80.6% [125/155] at 0.5 mg BID, and 80.1% [125/156] at 1 mg BID) than placebo subjects (71.4% [110/154]). The 3 most prevalent AEs at varenicline 1 mg BID were nasopharyngitis (35.9% [56/156]), nausea (24.4% [38/156]), and headache (10.3% [16/156]), all of which were of mild or moderate intensity. Nausea was the only AE that appeared dose related (7.2% [11/153] at 0.25 mg BID, 9.7% [15/155] at 0.5 mg BID, and 24.4% [38/156] at 1 mg BID) versus placebo (7.8% [12/154]). Varenicline was associated with dose-dependent improvement in smoking abstinence rates during the last 4 weeks of treatment and in the longer term over 40 weeks of nontreatment follow-up. The dose associated with the highest efficacy was varenicline 1 mg BID.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

A randomized controlled open comparative trial of varenicline vs nicotine patch in adult smokers: efficacy, safety and withdrawal symptoms (the VN-SEESAW study).

It has been suggested that anti-smoking therapy gives encouraging results, but this has not been verified by well-randomized study protocols. The present study was a randomized controlled trial of varenicline vs nicotine patch in adult smokers for comparison of efficacy, safety and withdrawal symptoms. The 32 adult smokers were randomly divided into a varenicline group (VG, n=16) and a nicotine patch group (NG, n=16). The primary endpoints were the 12- and 24-week smoking-abstinence rates, safety and withdrawal symptoms including stress. No significant difference in abstinence rates was observed between the 2 groups over weeks 9-12 (71.4% vs 78.6% in the VG and NG, respectively), and weeks 9-24 (64.3% vs 71.4%, respectively). The frequencies of inability to concentrate at 2, 4, and 8 weeks, and wakeful nights at 2 weeks were higher in the VG than in the NG. Adverse side-effects associated with a gastrointestinal disorder occurred in 14 cases and 1 case in the VG and NG, respectively, and skin allergy was seen in 0 and 9 cases, respectively. The selection of treatment depends on the balance of desired acuteness of cessation of smoking and side-effects, such as psychiatric and gastrointestinal problems or skin allergy.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial.

Smoking cessation is a key component of secondary cardiovascular disease prevention. Varenicline, a partial alpha4beta2 nicotinic acetylcholine receptor agonist, is effective for smoking cessation in healthy smokers, but its efficacy and safety in smokers with cardiovascular disease are unknown. A multicenter, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease. Participants received varenicline (1 mg twice daily) or placebo, along with smoking-cessation counseling, for 12 weeks. Follow-up lasted 52 weeks. The primary end point was carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 (last 4 weeks of treatment). The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 (47.0% versus 13.9%; odds ratio, 6.11; 95% confidence interval [CI], 4.18 to 8.93) and weeks 9 through 52 (19.2% versus 7.2%; odds ratio, 3.14; 95% CI, 1.93 to 5.11). The varenicline and placebo groups did not differ significantly in cardiovascular mortality (0.3% versus 0.6%; difference, -0.3%; 95% CI, -1.3 to 0.7), all-cause mortality (0.6% versus 1.4%; difference, -0.8%; 95% CI, -2.3 to 0.6), cardiovascular events (7.1% versus 5.7%; difference, 1.4%; 95% CI, -2.3 to 5.0), or serious adverse events (6.5% and 6.0%; difference, 0.5%; 95% CI, -3.1 to 4.1). As a result of adverse events, 9.6% of varenicline and 4.3% of placebo participants discontinued study drug. Varenicline is effective for smoking cessation in smokers with cardiovascular disease. It was well tolerated and did not increase cardiovascular events or mortality; however, trial size and duration limit definitive conclusions about safety. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov/ct2/show/NCT00282984. Unique identifier: NCT00282984.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial.

To determine whether self-regulated flexible dosing with varenicline tartrate is safe and effective for smoking cessation. 320 healthy, motivated-to-quit smokers (> or =10 cigarettes/day) aged 18-65 years, entered a multicenter, randomized, double-blind, placebo-controlled study - conducted between December 26, 2001 and June 24, 2003 - with a 12-week treatment phase and 40-week, double-blind, non-treatment follow-up. Treatment consisted of varenicline or placebo in fixed doses (Week 1: titrated from 0.5 to 1.0 mg/day) followed by a self-regulated flexible schedule (Weeks 2-12: 0.5-2.0 mg/day). Primary outcomes included carbon monoxide-confirmed continuous abstinence rate (CAR) from smoking for Weeks 4 through 7, 9 through 12, and 9 through 52. Secondary outcomes included CAR from Weeks 9 through 24, 7-day point prevalence of abstinence, safety assessments, and measures of craving, withdrawal, and smoking reward. Superior CARs were observed in varenicline-treated (n = 157) versus placebo participants (n=155) for Weeks 4 through 7 (38.2 vs. 11.6%), 9 through 12 (40.1 vs. 11.6%), 9 through 24 (28.0 vs. 9.0%), and 9 through 52 (22.3 vs. 7.7%) (all p<0.001). Seven-day point prevalence was higher in varenicline-treated than placebo participants at Weeks 12 (46.5 vs. 14.2%; p<0.001), 24 (32.5 vs. 13.5%; p<0.001), and 52 (28.0 vs. 13.5%; p=0.001). Overall, medication compliance was high, although varenicline-treated, but not placebo, participants tended to taper down their dosage over time. Total treatment-emergent AEs were 77.1% (varenicline: 121/157) and 65.8% (placebo: 102/155). Few AEs led to treatment discontinuation (varenicline: 11/157, 7.0% and placebo: 7/155, 4.5%). Participants were primarily healthy Caucasians, so more research is necessary to determine how applicable these findings are to other populations. A self-regulated, flexible dosing regimen of varenicline is well tolerated, with superior effectiveness versus placebo for smoking cessation.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

[Cytisine (Tabex) as a pharmaceutical aid in stopping smoking].

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial.

The majority of cigarette smokers who achieve abstinence relapse within the first year and require many attempts before achieving permanent abstinence. Evidence to support pharmacological treatment for relapse prevention is insufficient. To determine whether smokers who quit after 12 weeks of treatment with varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, maintain greater continuous abstinence rates (defined as not a single "puff" of a cigarette) than placebo controls during an additional 12 weeks of treatment and until 52 weeks after treatment initiation. Randomized controlled trial conducted at multiple medical clinics in 7 countries with follow-up to 52 weeks after study baseline. Of 1927 cigarette smokers recruited between April 2003 and February 2004 and treated for 12 weeks with open-label varenicline titrated to 1 mg twice per day, 1236 (64.1%) did not smoke, use tobacco, or use nicotine replacement therapy during the last week of treatment and 62.8% (n = 1210) were randomized to additional treatment or placebo. Participants were randomly assigned to receive either double-blind varenicline, 1 mg twice per day (n = 603), or placebo (n = 607) for an additional 12 weeks. Carbon monoxide-confirmed continued abstinence during weeks 13 to 24 and weeks 13 to 52 of the study. The carbon monoxide-confirmed continuous abstinence rate was significantly higher for the varenicline group than for the placebo group for weeks 13 to 24 (70.5% vs 49.6%; odds ratio [OR], 2.48; 95% confidence interval [CI], 1.95-3.16; P<.001) as well as for weeks 13 to 52 (43.6% vs 36.9%; OR, 1.34; 95% CI, 1.06-1.69; P = .02). Adverse events reported in the open-label period were mostly mild; no difference in adverse events between varenicline and placebo was observed during the double-blind period. Smokers who achieved abstinence for at least 7 days at the end of 12 weeks of open-label varenicline treatment and were randomized to receive an additional 12 weeks of varenicline treatment showed significantly greater continuous abstinence in weeks 13 to 24 compared with placebo. This advantage was maintained through the nontreatment follow-up to week 52. Varenicline may be an efficacious, safe, and well-tolerated agent for maintaining abstinence from smoking. clinicaltrials.gov Identifier: NCT00143286.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial.

Smoking is the most important risk factor for COPD and accelerates its progression. Despite the health implications, a large proportion of patients with COPD continue to smoke, so finding effective smoking cessation interventions for this population is paramount. To our knowledge, this is the first randomized clinical trial to compare the efficacy and safety of varenicline tartrate vs placebo in smokers with mild to moderate COPD. In a 27-center, double-blind, multinational study, 504 patients with mild to moderate COPD (postbronchodilator FEV1/FVC, <70%; FEV1 percent predicted normal value, ≥50%) and without known psychiatric disturbances were randomized to receive varenicline (n=250) or placebo (n=254) for 12 weeks, with a 40-week nontreatment follow-up. The primary end point was carbon monoxide-confirmed continuous abstinence rate (CAR) for weeks 9 to 12. A secondary end point was CAR for weeks 9 to 52. CAR for weeks 9 to 12 was significantly higher for patients in the varenicline group (42.3%) than for those in the placebo group (8.8%) (OR, 8.40; 95% CI, 4.99-14.14; P<.0001). CAR in the patients treated with varenicline remained significantly higher than in those treated with placebo through weeks 9 to 52 (18.6% vs 5.6%) (OR, 4.04; 95% CI, 2.13-7.67; P<.0001). Nausea, abnormal dreams, upper-respiratory tract infection, and insomnia were the most commonly reported adverse events (AEs) for patients in the varenicline group. Serious AEs were infrequent in both treatment groups. Two patients in the varenicline group and one patient in the placebo group died during the study. Reports of psychiatric AEs were similar for both treatment groups. Varenicline was more efficacious than placebo for smoking cessation in patients with mild to moderate COPD and demonstrated a safety profile consistent with that observed in previous trials. Trial registry: ClinicalTrials.gov; No.: NCT00285012; URL: www.clinicaltrials.gov.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

A double-blind study evaluating the long-term safety of varenicline for smoking cessation.

We assessed the safety of long-term varenicline administration for smoking cessation. In this randomized, double-blind, multicenter trial, eligible adult smokers (18-75 years) who smoked an average of > or =10 cigarettes/day were randomized to either varenicline 1 mg twice daily (BID) or placebo for 52 weeks. Subjects made weekly clinic visits until week 8, and then every 4 weeks until week 52, with a follow-up visit at week 53. The target quit date was the morning of the week 1 clinic visit. Brief counseling was provided at each visit, and vital signs, adverse events (AEs), and smoking status were documented. Other laboratory measures were collected at specified visits. A total of 251 subjects were randomized to varenicline and 126 to placebo. Approximately half of the subjects in each arm completed the study (53.8% varenicline; 46.8% placebo). Treatment-emergent AEs were observed in 96.4% of varenicline- and 82.5% of placebo-treated subjects during the study. Common varenicline-associated AEs were nausea (40.2%), abnormal dreams (22.7%), and insomnia (19.1%). Most AEs were considered mild or moderate in intensity. AEs leading to discontinuation of varenicline treatment included nausea (7.6%), insomnia (3.2%), and abnormal dreams (2.4%). A single varenicline-related serious AE, bilateral subcapsular cataracts, was observed. At week 52, 7-day point prevalence abstinence rates were 36.7% (varenicline) and 7.9% (placebo). Varenicline 1 mg BID can be safely administered for up to 1 year. Varenicline was also a more effective smoking cessation aid than placebo throughout the study, supporting both its short- (12-week) and long-term (52-week) efficacy.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.

The alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel alpha4beta2 nAChR partial agonist, may be beneficial for smoking cessation. To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo. Randomized, double-blind, parallel-group, placebo- and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (> or =10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising. Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n = 352), bupropion SR titrated to 150 mg twice per day (n = 329), or placebo (n = 344) orally for 12 weeks, with 40 weeks of nondrug follow-up. Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52. For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P = .057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]). Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks. clinicaltrials.gov Identifier: NCT00141206.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates.

Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication. In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24. Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively). Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

Tobacco dependence treatment for hospitalized smokers: a randomized, controlled, pilot trial using varenicline.

The hospital can be an important opportunity for smoking cessation interventions. This is the first randomized, double-blinded, placebo-controlled pilot trial utilizing varenicline and post-discharge, in-person behavioral treatment for hospitalized smokers. Seventy-nine smokers admitted to a university-based hospital with various diagnoses were enrolled from 2007 to 2009. The primary outcome was biochemically confirmed abstinence at 24 weeks following discharge. Secondary outcomes included withdrawal symptoms, motivation, utilization of treatment, and medical events. Overall abstinence at 24 weeks was 27% with no difference between varenicline and placebo treatment groups (23% vs. 31%). There were no significant differences in motivation to stop smoking or withdrawal symptoms. Over 40% of all subjects utilized post-discharge behavioral treatment with significantly higher abstinence rates compared with those who did not (53.1% vs. 8.5%, p<0.01). Overall adverse events were similar in both treatment groups with the only significant difference being more nausea in the varenicline group (25% vs. 5%; p<0.01). Twenty-three subjects were re-hospitalized with no significant differences between treatment groups (13 varenicline vs. 10 placebo). This pilot trial of varenicline in hospitalized smokers demonstrated feasibility of implementation, produced some hypothesis-generating findings, and suggested the potential benefit of face-to-face treatment following discharge. Copyright © 2011 Elsevier Ltd. All rights reserved.

CD006103

Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out. Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.

A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers.

Rates of smoking in East Asian men range from >35% to >60%, and are increasing in women and the young. This study evaluated the efficacy and tolerability of 1 mg BID varenicline, a novel alpha4beta2 nicotinic acetylcholine receptor partial agonist, for smoking cessation in smokers in Taiwan and Korea. A randomized, double-blind, placebo-controlled, 12-week treatment, 12-week follow-up trial was conducted at 5 sites each in Korea and Taiwan. Eligible subjects, smoking >or=10 cigarettes/d, received brief smoking-cessation counseling and were randomly assigned in a 1:1 ratio to varenicline 1 mg BID (titrated during the first week) or placebo. Smoking status was established by self-report and confirmed at clinic visits by end-expiratory carbon monoxide <or=10 ppm. The primary end point was continuous abstinence rate (CAR) during the last 4 weeks of treatment. Secondary end points included CAR from weeks 9 to 24 and 7-day point prevalence (PP) of abstinence at weeks 12 and 24. Craving, withdrawal, and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal Scale, the Brief Questionnaire of Smoking Urges, and the modified Cigarette Evaluation Questionnaire. Observed or volunteered adverse-event data were recorded at clinic visits. Overall, 126 subjects (84.9% male) received varenicline, and 124 (92.7% male) received placebo, Subjects were aged 21 to 73 years (mean age, 39.7 and 40.9 years for varenicline and placebo groups, respectively), and the mean (range) body weights were 69.0 (44.8-110.0) kg and 71.4 (45.5-102.0) kg, respectively. Subjects had smoked for 3 to 52 years (mean, 20.2 and 22.1 years in the varenicline and placebo groups, respectively). Subjects had smoked a mean of 23 cigarettes/d over the past month, with 51.6% (varenicline) and 46.0% (placebo) having made 1 or more prior serious quit attempts. Smoking-cessation rates at the end of treatment were 59.5% with varenicline versus 32.3% with placebo (P < 0.001). CARs through 12 weeks post-treatment (weeks 9-24) were 46.8% with varenicline and 21.8% with placebo (P < 0.001). The 7-day PP was 67.5% with varenicline versus 36.3% with placebo at week 12, and 57.1% versus 29.0% with placebo at week 24 (both, P < 0.001). Treatment-emergent, all-causality adverse events with an incidence >or= 5% for varenicline were nausea (43.7% for varenicline vs 11.3% placebo), insomnia (15.1% vs 13.7%), increased appetite (7.9% vs 6.5%), constipation (7.1% vs 2.4%), anxiety (5.6% vs 2.4%), and abnormal dreams (5.6% vs 0.8%). Adverse events resulted in <10% treatment discontinuations overall. Varenicline was an efficacious and well-tolerated pharmacotherapy for smoking cessation in this group of Asian smokers over a 12-week treatment period, and its effects persisted for a further 12-week follow-up period.

CD004079

There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.

Low-dose aspirin and incidence of colorectal tumors in a randomized trial.

Laboratory, clinical, and epidemiologic studies have recently suggested that regular use of aspirin can reduce colorectal cancer incidence or mortality. However, observational epidemiologic analyses have had limited opportunity to control for confounding bias or to specify aspirin doses used. Our purpose was to examine the relationship between regular use of low-dose aspirin and incidence of invasive and noninvasive colorectal tumors by utilizing data from the Physicians' Health Study, a randomized, double-blinded, placebo-controlled trial of aspirin and beta carotene. We also attempted to determine whether invasive cancers among aspirin users were associated with rectal bleeding and early stage at diagnosis. The Physicians' Health Study includes 22071 U.S. male physicians. The aspirin arm was terminated in 1988 after a mean follow-up of 5 years. Stage at diagnosis and signs and/or symptoms during presentation were abstracted from medical records. Cox proportional hazards models were used to estimate relative risk (RR), 95% confidence intervals (CIs), and the association between aspirin and bleeding. Differences between aspirin and placebo groups in tumor risk over time were visualized with Kaplan-Meier curves. We assessed the association between aspirin and stage at diagnosis with a Mann-Whitney rank sum statistic for non-parametric comparison of two ordinal distributions. The RR of developing colorectal cancer for aspirin compared with placebo was 1.15 (95% CI = 0.80-1.65). For in situ cancers and polyps, the RR was 0.86 (95% CI = 0.68-1.10). There was no significant trend for decreasing RR by year of follow-up for invasive cancers (P = .09) or noninvasive tumors (P = .96). Aspirin and placebo groups did not differ in stage or prevalence of rectal bleeding at diagnosis. Regular aspirin use, at a dose adequate for preventing myocardial infarction, was not associated with a substantial reduction in the incidence of colorectal cancer during 5 years of randomized treatment and follow-up. A small decrease in polyps in the aspirin group could not be reliably distinguished from a chance association. Our results suggest that among low-dose aspirin users, (a) colorectal cancer mortality is not likely to be reduced by earlier detection and (b) incidence is not likely to be increased due to aspirin-induced gastrointestinal bleeding. The potential for a benefit from higher doses of aspirin or longer duration of use should be addressed by more detailed observational epidemiologic studies and prevention trials with longer follow-up of randomized participants.

CD004079

There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.

The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.

Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.

CD004079

There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.

A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer.

Experimental studies in animals and observational studies in humans suggest that regular aspirin use may decrease the risk of colorectal adenomas, the precursors to most colorectal cancers. We conducted a randomized, double-blind trial to determine the effect of aspirin on the incidence of colorectal adenomas. We randomly assigned 635 patients with previous colorectal cancer to receive either 325 mg of aspirin per day or placebo. We determined the proportion of patients with adenomas, the number of recurrent adenomas, and the time to the development of adenoma between randomization and subsequent colonoscopic examinations. Relative risks were adjusted for age, sex, cancer stage, the number of colonoscopic examinations, and the time to a first colonoscopy. The study was terminated early by an independent data and safety monitoring board when statistically significant results were reported during a planned interim analysis. A total of 517 randomized patients had at least one colonoscopic examination a median of 12.8 months after randomization. One or more adenomas were found in 17 percent of patients in the aspirin group and 27 percent of patients in the placebo group (P=0.004). The mean (+/-SD) number of adenomas was lower in the aspirin group than the placebo group (0.30+/-0.87 vs. 0.49+/-0.99, P=0.003 by the Wilcoxon test). The adjusted relative risk of any recurrent adenoma in the aspirin group, as compared with the placebo group, was 0.65 (95 percent confidence interval, 0.46 to 0.91). The time to the detection of a first adenoma was longer in the aspirin group than in the placebo group (hazard ratio for the detection of a new polyp, 0.64; 95 percent confidence interval, 0.43 to 0.94; P=0.022). Daily use of aspirin is associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer. Copyright 2003 Massachusetts Medical Society

CD004079

There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.

A randomized trial of aspirin to prevent colorectal adenomas.

Laboratory and epidemiologic data suggest that aspirin has an antineoplastic effect in the large bowel. We performed a randomized, double-blind trial of aspirin as a chemopreventive agent against colorectal adenomas. We randomly assigned 1121 patients with a recent history of histologically documented adenomas to receive placebo (372 patients), 81 mg of aspirin (377 patients), or 325 mg of aspirin (372 patients) daily. According to the protocol, follow-up colonoscopy was to be performed approximately three years after the qualifying endoscopy. We compared the groups with respect to the risk of one or more neoplasms (adenomas or colorectal cancer) at least one year after randomization using generalized linear models to compute risk ratios and 95 percent confidence intervals. Reported adherence to study medications and avoidance of nonsteroidal antiinflammatory drugs were excellent. Follow-up colonoscopy was performed at least one year after randomization in 1084 patients (97 percent). The incidence of one or more adenomas was 47 percent in the placebo group, 38 percent in the group given 81 mg of aspirin per day, and 45 percent in the group given 325 mg of aspirin per day (global P=0.04). Unadjusted relative risks of any adenoma (as compared with the placebo group) were 0.81 in the 81-mg group (95 percent confidence interval, 0.69 to 0.96) and 0.96 in the 325-mg group (95 percent confidence interval, 0.81 to 1.13). For advanced neoplasms (adenomas measuring at least 1 cm in diameter or with tubulovillous or villous features, severe dysplasia, or invasive cancer), the respective relative risks were 0.59 (95 percent confidence interval, 0.38 to 0.92) and 0.83 (95 percent confidence interval, 0.55 to 1.23). Low-dose aspirin has a moderate chemopreventive effect on adenomas in the large bowel. Copyright 2003 Massachusetts Medical Society

CD004079

There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.

Effect of sulindac on sporadic colonic polyps.

We sought to determine in a double-blinded, placebo-controlled study if the nonsteroidal anti-inflammatory drug sulindac causes regression of sporadic colonic polyps. The impetus for this study is the profound regressive effect of sulindac on polyps in familial adenomatous polyposis. Asymptomatic patients undergoing routine screening flexible sigmoidoscopy were enrolled if they had polyps of < or = 1 cm in size. Of 162 patients screened, 22 patients were randomly enrolled to take 150 mg of sulindac twice daily, and 22 patients took a placebo. Treatment duration was 4 months and was followed by colonoscopy with removal of all polyps. Four patients were dropped from the study (sulindac group) due to urosepsis (1 patient), heartburn (2 patients), and anemia (1 patient). Compliance (determined by monthly pill counting), mean age, and the effect of sulindac vs. placebo on polyp regression or size were not statistically different in the two treatment groups. Analysis of our data indicated that there is only a 0.8% chance that the probability of polyp regression with sulindac is as large as 50%. Four months of treatment with sulindac does not result in a clinically significant regression of sporadic colonic polyps, although a small effect may not have been detected by the size of our study. Our data suggest that the biological response of sporadic and familial polyposis polyps to sulindac is different.

CD004079

There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.

Primary chemoprevention of familial adenomatous polyposis with sulindac.

Familial adenomatous polyposis is caused by a germ-line mutation in the adenomatous polyposis coli gene and is characterized by the development of hundreds of colorectal adenomas and, eventually, colorectal cancer. Nonsteroidal antiinflammatory drugs can cause regression of adenomas, but whether they can prevent adenomas is unknown. We conducted a randomized, double-blind, placebo-controlled study of 41 young subjects (age range, 8 to 25 years) who were genotypically affected with familial adenomatous polyposis but phenotypically unaffected. The subjects received either 75 or 150 mg of sulindac orally twice a day or identical-appearing placebo tablets for 48 months. The number and size of new adenomas and side effects of therapy were evaluated every four months for four years, and the levels of five major prostaglandins were serially measured in biopsy specimens of normal-appearing colorectal mucosa. After four years of treatment, the average rate of compliance exceeded 76 percent in the sulindac group, and mucosal prostaglandin levels were lower in this group than in the placebo group. During the course of the study, adenomas developed in 9 of 21 subjects (43 percent) in the sulindac group and 11 of 20 subjects in the placebo group (55 percent) (P=0.54). There were no significant differences in the mean number (P=0.69) or size (P=0.17) of polyps between the groups. Sulindac did not slow the development of adenomas, according to an evaluation involving linear longitudinal methods. Standard doses of sulindac did not prevent the development of adenomas in subjects with familial adenomatous polyposis.

CD004079

There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.

Sulindac causes regression of rectal polyps in familial adenomatous polyposis.

In familial adenomatous polyposis, sulindac-induced polyp regression has been reported by several authors. In this study, the goal was to confirm these results by a randomized, placebo-controlled, double-blind crossover study in 10 patients with rectal polyps that had been previously treated by colectomy and ileorectal anastomosis. Patients received sulindac, 300 mg/day, or placebo during two 4-month periods separated by a 1-month wash-out phase. One patient was not compliant and was excluded. With sulindac, the authors observed a complete (6 patients) or almost complete (3 patients) regression of the polyps. With placebo, the authors observed an increase (5 patients), no change (2 patients), and a relative decrease (2 patients) in the number of polyps. The difference between sulindac and placebo was statistically significant (P less than 0.01). In biopsy specimens of polyps and normal rectal mucosa of 6 patients, the authors conducted an immunohistochemical study of the cellular proliferation index using the Ki 67 monoclonal antibody (Ki 67 index), at the beginning and at the end of each treatment period. They were not able to show a sulindac-induced modification of the Ki 67 index. The authors conclude that sulindac is effective in inducing the regression of rectal polyps in familial adenomatous polyposis.

CD004079

There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.

Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial.

Epidemiologic and experimental studies have suggested that aspirin intake reduces the risk for colorectal carcinogenesis. However, the available data are not sufficient to serve as the basis for firm recommendations. We randomly assigned 272 patients with a history of colorectal adenomas (at least one more than 5 mm in diameter, or more than 3) to daily lysine acetylsalicylate (160 or 300 mg/day) or placebo for 4 years. The primary end points were adenoma recurrence after 1 and 4 years. These results are those of the year 1 colonoscopy. Among the 238 patients who completed the year 1 colonoscopy, at least one adenoma was observed in 38 patients of the 126 (30%) in the aspirin group and in 46 of the 112 (41%) in the placebo group; relative risk was 0.73 (95% confidence interval [CI]: 0.52-1.04; P = 0.08). At least one adenoma of more than 5 mm diameter was observed in 13 patients (10%) in the aspirin group and 26 (23%) in the placebo group (P = 0.01). The corresponding numbers for adenomas more than 10 mm in diameter were one (1%) and 7 (6%) (P = 0.05). Stepwise regression showed that independent factors associated with lower adenoma recurrence are aspirin treatment (adenoma >5 mm, P = 0.01), absence of personal history of adenoma before the entry colonoscopy (P = 0.01), and initial adenomatous polyp burden less than 10 mm (P = 0.001). Daily soluble aspirin is associated with a reduction in the risk for recurrent adenomas found at colonoscopy 1 year after starting treatment.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Single-dose oral ciprofloxacin versus placebo for prophylaxis during transrectal prostate biopsy.

To determine whether antimicrobial prophylaxis could prevent infections after transrectal needle biopsy of the prostate using automated biopsy devices. We conducted a prospective, randomized, double-blind, multicenter trial in which a total of 537 patients received either oral ciprofloxacin 500 mg or placebo before transrectal needle biopsy of the prostate. Repeated urine cultures and urinalysis were obtained at 2 to 6 days after biopsy and 9 to 15 days after biopsy. The primary determinant of efficacy was bacteriologic response (bacteriuria [more than 10(4) colony-forming units (CFU)/mL] versus no bacteriuria) at the 9- to 15-day follow-up evaluation. Two hundred twenty-seven (84%) of 269 ciprofloxacin patients and 230 (86%) of 268 placebo patients were valid for efficacy analysis in which a mean of four biopsies was performed. Six ciprofloxacin-treated (3%) and 19 placebo-treated (8%) patients had bacteriuria (more than 10(4) CFU/mL) after the procedure (P = 0.009). Six ciprofloxacin recipients (3%) and 12 placebo recipients (5%) had clinical signs and symptoms of a urinary tract infection (UTI) (P = 0.15). In addition, no ciprofloxacin-treated patients compared with 4 placebo-treated patients (2%) were admitted to the hospital for febrile UTI after the procedure. Ciprofloxacin reduced the expected net costs of treating infectious complications after biopsy by $23 per patient for an overall annual savings of $68,195 in the five study groups when compared with placebo. Single-dose oral ciprofloxacin reduced bacteriuria after biopsy compared with placebo in patients undergoing transrectal prostatic biopsy and provided an economic advantage. In addition, this study establishes the actual rate of bacteriuria after transrectal needle biopsy of the prostate without antibiotic prophylaxis to be 8% with a clinical rate of UTI of 5% and a hospitalization rate of 2%.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Prophylaxis for transrectal prostatic biopsies: a randomized controlled study of intravenous co-amoxiclav given as a single dose compared with an intravenous dose followed by oral co-amoxiclav for 24 h.

To compare in a randomized prospective study the infective complication rates of a single intravenous dose of co-amoxiclav given alone before transrectal prostatic biopsy with an intravenous dose followed by oral co-amoxiclav for 24 h. Eighty-three patients undergoing prostatic biopsy were randomized to receive 1.2 g co-amoxiclav intravenously and then either three further doses of oral co-amoxiclav (Group 1) or no further antibiotics (Group 2). The evaluation included analysis of a mid-stream urine (MSU) sample before and 72 h after biopsy, and the recording of oral temperatures and symptoms in the first 44 patients. Patients with symptomatic urinary tract infections (UTIs), prostatitis, indwelling catheters, diabetes and those receiving steroid therapy were excluded. Eight patients, four from each treatment arm, were found to have asymptomatic UTIs from their MSU before biopsy. Excluding these patients, four patients (11%) from Group 1 and six from Group 2 (16%) had positive MSUs at 72 h; two patients from Group 2 and one from Group 1 required admission to hospital. Of the patients returning symptom and temperature charts, a further six (14%; three from each group) reported signs and symptoms suggestive of infection despite negative urine cultures. There was no statistically significant difference in the rate of positive MSUs between the groups. The incidence of infections was considerably higher than in previously published series where other antibiotics were used, suggesting that co-amoxiclav is not the drug of choice for transrectal prostatic biopsy.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

[Short or long schemes of antibiotic prophylaxis for prostate biopsy. A multicentre prospective randomised study].

We compared the incidence of the Urinary Tract Infection between a single preoperative dose and a three-day antibiotic prophylaxis regimen for transrectal ultrasound guided biopsy in randomized multicenter trial. Between February 2006 and December 2007, 322 men who underwent transrectal ultrasound-guided prostate biopsy were included in a multicentre prospective randomised study. Patients received antibiotic prophylaxis by ciprofloxacin orally, either 1g single dose two hours before the biopsy (Group 1: n=139) or a prolonged prophylaxis for three days (Group 2: n=149). Assessment five days before and five days following the biopsy included a clinical examination, biological tests and a self-questionnaire. Two patients developed prostatitis, one in each group: 0.75% of the first group, 0.69% of the second. Twelve developed asymptomatic bacteriuria, six in each group: 4.51% of the first group and 4.19% of the second. There was no significant difference between the two groups (Fisher test; p>0.9). There was no significant difference between the two antibiotic prophylaxis regimen (one single dose or three days) for patients undergoing TRUS guided biopsies. Therefore, the single preoperative dose should be the preferred option.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Bacteremia and bacteriuria after transrectal prostatic biopsy.

To determine the efficacy of parenteral gentamicin versus povidone-iodine enema (P.I.E.) in preventing infectious complications, a randomized study was undertaken in 40 patients undergoing transrectal needle prostatic biopsy. In 69 per cent of patients not receiving P.I.E. bacteremia developed, and 32 per cent acquired bacteriuria; whereas only 19 per cent of patients given P.I.E. alone or in combination with gentamicin because bacteremic, and 9.5 per cent had postbiopsy bacteriuria. Thus, P.I.E. provided a safe and effective means for preventing most bacteremia and bacteriuria associated with transrectal biopsy of the prostate.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Comparison of a 3-day with a 1-day regimen of an extended-release formulation of ciprofloxacin as antimicrobial prophylaxis for patients undergoing transrectal needle biopsy of the prostate.

To compare the clinical and bacteriological efficacy and the clinical safety of a 1-day with a 3-day regimen of an extended-release formulation of ciprofloxacin (ciprofloxacin XR) given as antimicrobial prophylaxis to men undergoing transrectal needle biopsy of the prostate (TRNBP). This was a multicentre, prospective, international, double-blind study in patients who required TRNBP. Patients were randomized to receive oral ciprofloxacin XR 1000 mg as either a 1-day or a 3-day regimen. Single doses were given at 24 h before, 2-3 h before, and 24 h after TRNBP. Patients in the 1-day regimen had placebo instead of the first and third doses of ciprofloxacin. Of 497 patients enrolled, 247 were randomized to 1-day ciprofloxacin XR and 250 to the 3-day regimen. In the population valid for microbiological efficacy, the final assessment identified bacteriological success (primary efficacy endpoint) in more patients who had the 3-day regimen (98%) than in those who received the 1-day regimen (94.8%, 95% confidence interval, CI, - 6.1%, 0.8%), although the difference was not statistically significant. In this population, the clinical response at the final visit was 98.5% and 96.7% for patients receiving the 3-day and the 1-day regimens, respectively (95% CI - 5.2%, 0.8%). However, in the clinical efficacy population the clinical success rate was significantly greater for the 3-day (99.0%) than for the 1-day regimen (95.8%; 95% CI - 6.4%, - 0.3%). In a multivariate analysis, patients with diabetes mellitus and patients with a history of prostatitis had higher microbiological and clinical failure rates, respectively, than those without such conditions. For these patients, all failures occurred among those treated with the 1-day regimen. As defined by bacteriological success in the population assessed for microbiological efficacy, prophylaxis with one dose of ciprofloxacin XR was statistically no worse than a 3-day regimen. However, in all efficacy analyses, bacteriological and clinical success rates were consistently lower for the 1-day than for the 3-day treatment. Thus, for selected patients undergoing TRNBP, there might be a role for 3-day preventive therapy with ciprofloxacin XR.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Prevention of urinary tract infection and sepsis following transrectal prostatic biopsy.

Transrectal biopsy is one of the more popular methods for the diagnosis of prostatic cancer. However, there is disagreement as to whether the use of prophylactic antimicrobials decreases the incidence of fever and urinary tract infections, which may follow this procedure. A prospective randomized double-blind study involving 63 patients was instituted to determine the efficacy of carbenicillin indanyl sodium in reducing these complications. The protocol consisted of administration of 2 tablets of 4 times daily of a placebo or the treatment drug 24 hours before and after biopsy. Clean catch urine cultures were obtained 24 hours before biopsy and at 48 hours and 2 weeks after the procedure. Blood cultures were performed 15 minutes after biopsy. In addition, clinical parameters were monitored closely in the hospital for 48 hours after biopsy. A total of 48 patients was considered evaluable. Of 23 patients who received the study drug 2 (8.6 per cent) had positive urine cultures at 48 hours compared to 9 of 25 (36 per cent) from the placebo group. A similar result was observed from the 2-week culture data, in which 2 of 23 patients (8.6 per cent) in the treatment group had positive urine cultures as opposed to 5 of 25 (20 per cent) receiving the placebo. Fever occurred in 48 per cent of the placebo and in 17 per cent of the carbenicillin groups. Our data indicate that prophylactic administration of carbenicillin indanyl sodium decreases the complications of fever and urinary tract infections following transrectal biopsy of the prostate.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

[Clinical significance of antibiotic prophylaxis for transrectal prostate biopsy].

To evaluate the efficacy and safety of single-dose oral antibiotic prophylaxis in the Between prevention of post-procedure infections in patients undergoing transrectal prostate biopsy. September 1998 and March 2001, a total of 192 patients who had an abnormal digital rectal examination and/or prostate specific antigen 4 ng/ml or greater underwent transrectal ultrasound guided systematic 13 cores prostate biopsy. The patients were randomly divided into three groups. Group A (62) received a placebo (Vit C) tablet twice a day for 3 days, group B (64) a single dose of ciprofloxacin (0.5 g) and metronidazole (0.4 g), and group C (66) the same combination twice a day for 3 days. Urine cultures were obtained 48 h after the biopsy and blood cultures when patients who developed fever. Noninfective complications included were rectal bleeding, haematuria and pain. Infective complications included urinary tract infection and fever. There was no significant difference among the three groups in noninfective complications but the incidence of infective complications in group A was significantly higher than in groups B and C (P < 0.01). There was no significant difference among group B and C in infective complications (P > 0.05). Our study shows single-dose oral antibiotic prophylaxis is effective and safe to prevent infectious complications follow transrectal prostate biopsy.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Prospective assessment of the efficacy of single dose versus traditional 3-day antimicrobial prophylaxis in 12-core transrectal prostate biopsy.

To prospectively evaluate the efficacy of single dose antibiotic prophylaxis in 12-core transrectal ultrasonography (TRUS) guided prostate biopsy. A total of 400 patients who underwent prostate biopsy with TRUS guidance were included. The patients were prospectively randomized in three groups regarding antibiotic prophylaxis. The first group (139 patients) received a single gram of intramuscular ceftriaxone, while the second group (131 patients) had a 3-day course of oral ciprofloxacin. The third group (130 patients) had single oral 500 mg of ciprofloxacin. All patients had urine cultures prior to biopsy and on the second day after biopsy. The study groups were compared in terms of the results of urine cultures and clinical parameters. Overall, only seven patients (1.8% of the cases) had positive urine cultures with no difference between these three groups. Additionally, no significant difference was observed regarding morbidity rates in all groups. Only eight patients (2%) developed major complications requiring hospitalization. There was no increase in the rate of infectious complications when the biopsy core numbers were increased up to 12. The current study suggests that a single oral dose of antimicrobial prophylaxis is reasonable in TRUS prostate biopsy even in the case of 12-core sampling.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

A randomized comparative study of the prophylactic use of trimethoprim-sulfamethoxazole versus netilmycin-metronidazole in transrectal prostatic biopsy.

An open randomized study was done to compare the prophylactic value of single doses of netilmycin-metronidazole versus trimethoprim-sulfamethoxazole in the prevention of postoperative infections associated with transrectal prostatic biopsy. Of 117 patients enrolled in the study 101 were evaluated and of these patients 47 received netilmycin-metronidazole and 54 received trimethoprim-sulfamethoxazole. The bacteremia rate in the netilmycin-metronidazole group was 28% (13 of 47 patients) with a 95% confidence interval of 18 to 42% and in the trimethoprim-sulfamethoxazole group it was 37% (20 of 54) with a confidence interval of 26 to 50% (p = 0.43). None of the patients with bacteremia was symptomatic. Urinary tract infection rates were greater in the netilmycin-metronidazole group: 17% (8 of 47 patients) versus 2% (1 of 54) in the trimethoprim-sulfamethoxazole group, p = 0.01. Trimethoprim-sulfamethoxazole (cotrimoxazole) is a better choice as an antimicrobial prophylaxis for patients undergoing transrectal prostatic biopsy.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Antimicrobial prophylaxis for transrectal prostatic biopsy: a prospective randomized trial of cefuroxime versus piperacillin/tazobactam.

To compare the clinical and microbiological outcome of a single-dose administration of cefuroxime or combined piperacillin/tazobactam (PT) after transrectal prostatic core-biopsy (TPB) in a prospective, randomized, open-label study. Of 111 eligible men consecutively undergoing ultrasonographically guided TPB, 56 received 1.5 g cefuroxime and 55 received 4.5 g PT intravenously 20 min before the procedure. The anterior rectal wall was cleaned with an antiseptic swab and four biopsies were taken. Urine and blood cultures were evaluated before the procedure and again after 48 h, and oral temperature and symptoms recorded for 72 h after TPB. A clinically successful outcome (no symptoms to indicate urinary or systemic sepsis or pyrexia > or = 37.5 degrees C after TPB) was achieved in 100 of 108 men (92.6%), of whom 51 received cefuroxime and 49 PT. Microbiological success (no bacteriuria > 10(5) organisms/mL, or bacteraemia, after TPB) was observed in 98 of 103 men (95%), of whom 48 received PT and 50 cefuroxime. Bacteriuria was present 48 h after TPB in 5% of the men. One man randomized to receive cefuroxime became bacteraemic (with Escherichia coli) and required hospital admission. Four of the five microbiological failures were caused by organisms sensitive to the administered antimicrobial agent. No anaerobic organisms were cultured. The most common adverse event recorded was transient diarrhoea, reported by 16 men receiving PT and two receiving cefuroxime. With this prophylactic regimen, there was no significant difference in outcome between the groups. Most of the organisms isolated were sensitive to the administered antimicrobial agent. Thus, further reductions in sepsis after TPB may be achieved by the administration of additional oral antimicrobial prophylaxis.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Antibiotic prophylaxis for transrectal biopsy of the prostate: a prospective randomized study of the prophylactic use of single dose oral fluoroquinolone versus trimethoprim-sulfamethoxazole.

We investigated the efficacy of prophylactic use of single dose oral ofloxacin and trimethoprim-sulfamethoxazole regimens for transrectal prostate biopsy in 110 men. In the ofloxacin, trimethoprim-sulfamethoxazole and control groups, urinary infection was found in 2 (4.76%), 3 (6.66%) and 6 (26.08%) patients, respectively. Both of these antibiotic regimens produced a statistically significant reduction in urinary infection (p<0.02, p<0.05). Our study indicates that single dose fluoroquinolone or trimethoprim-sulfamethoxazole prophylaxis seems to be effective, practical and economical.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Antibiotic prophylaxis for transrectal needle biopsy of the prostate: a randomized controlled study.

To determine the effect of antibiotic prophylaxis on infective complications after transrectal needle biopsy of the prostate. Between June 1996 and September 1998, 231 patients who satisfied the inclusion and exclusion criteria entered the study; the patients were randomized into three groups. Each patient underwent transrectal needle biopsy of the prostate after a cleansing enema at 06:00 hours. Patients in group 1 (75) then received a placebo tablet twice a day for 3 days; those in group 2 (79) were given a single dose of ciprofloxacin (500 mg) and tinidazole (600 mg), while those in group 3 (77) were given the same combination twice a day for 3 days. Urine cultures were obtained 48 h after the biopsy and blood cultures only from patients who developed fever. The complications (categorized as infective or noninfective) occurring in the three groups were compared using the chi-square test. Noninfective complications included were lower urinary tract symptoms, rectal bleeding, haematuria and perineal pain. The infective complications included urinary tract infection and fever. There was no significant difference among the three groups in noninfective complications (27, 29 and 31 in groups 1-3, respectively) but the incidence of infective complications (19, six and eight, respectively) was significantly higher in group 1 (P = 0.003). However, the difference was significant only for urinary tract infection (P = 0.01) and not for fever. In selected patients a single dose of ciprofloxacin-tinidazole is adequate prophylaxis for transrectal needle biopsy of the prostate. The present urinary infection rate was higher if no antibiotics were used. Continuing the antibiotic prophylaxis for 3 days offered no benefit over single-dose prophylaxis.

CD006576

Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Efficacy of prophylactic antimicrobial regimens in preventing infectious complications after transrectal biopsy of the prostate.

In a prospective study on 81 patients undergoing transrectal needle biopsy of the prostate, the efficacy of prophylaxis in preventing postbiopsy infectious complications was determined. The patients were divided randomly into four groups, and a comparison of the rate of postbiopsy complications in each group was made. In 11 and 17% of the patients in Group A (n = 18) who received povidone-iodine enema alone, bacteriuria and bacteraemia, respectively, occurred. When parenteral piperacillin alone in Group B (n = 22) was administered, the rates of the same complications were 9 and 14%, respectively, while both rates were as low as 4% in Group C (n = 25) when piperacillin in combination with povidone-iodine enema was given. On the other hand, in 31 and 37.5% of the patients in Group D (n = 16), who served as controls, bacteriuria and bacteraemia developed. The study has thus shown that parenteral piperacillin in combination with povidone-iodine enema significantly reduces the incidence of infectious complications associated with transrectal prostatic biopsy.