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CD001281

Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma.

To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma. Randomized, double-blind, double-dummy, three-period crossover. Outpatients at a single center. Patients spent 1 night during screening and 2 nights during each study period in a sleep laboratory for completion of sleep studies. Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV1, 50 to 90% of predicted) and who required regular bronchodilator therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil were allowed into the study if their dosing remained constant throughout the study. Inhaled salmeterol (42 microg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 microg/mL), and placebo taken twice daily. Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p < or = 0.05) in maintaining nocturnal FEV1 levels and was superior to placebo (p < or = 0.05) in improving morning and evening peak expiratory flow (PEF) and in decreasing nighttime albuterol use. The use of salmeterol significantly increased the percentage of days and nights with no albuterol use and decreased daytime albuterol use compared with theophylline and placebo (p < or = 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p < 0.001) but not with theophylline. The effects on sleep architecture were similar across treatment groups. Salmeterol (but not theophylline) was associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration, reductions in albuterol use, and improvements in patient perceptions of sleep. No differences were seen in polysomnographic measures of sleep quality.

CD001281

Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

Comparison of second controller medications in addition to inhaled corticosteroid in patients with moderate asthma.

The objective of this study was to compare the efficacy and safety of the second controller medications (long-acting beta2-agonist, leukotriene receptor antagonist and sustained-release theophylline) used in addition to inhaler corticosteroid treatment in moderate persistent asthma. A total of 64 patients with asthma, in the moderate persistent asthma category, were divided into three groups. Patients, all of whom were concurrently using inhaled corticosteroid (Budesonide 400 microg twice daily), were treated for 3 months with either inhaled formoterol 9 microg twice daily (first group), oral zafirlukast 20 mg twice daily (second group), or sustained-release theophylline 400 mg once daily (third group). All of the patients were subjected to assessments on the subject of peak expiratory flow (PEF) variability, forced expiratory volume in 1 sec (FEV1), asthma symptom scores (daytime and night-time), supplemental terbutalin use, asthma exacerbations and adverse events. Over the 3-month treatment period. In all of the three groups, significant improvements were recorded in the lung function, asthma symptom scores and supplemental terbutalin use criteria, as a result oftreatments applied. Formoterol treatment resulted in significantly greater and earlier improvements compared with the other two groups in several criteria: PEF variability (17.9 +/- 2.5; 21.9 +/- 3.2; 23.7 +/- 3.3; P < 0.001); asthma symptom score (daytime) (1.6 +/- 0.5; 1 +/- 0.5; 2.0 +/- 0,5; P < 0.05); asthma symptom score (night-time) (1.2 +/- 0.4; 2.2 +/- 0.5; 16 +/- 0.6; P < 0001); and supplement alter butalin use (1.2 +/- 0.3; 1.8 +/- 0.5; 1.7 +/- 0.5; P < 0.05). However, at the end of the treatment, in all of the three groups studied, improvements were attained in overall asthma control and there was no statistical difference among the groups. Although there were no side effects which required the discontinuation of the treatment, it was observed that the maximum side effect was in the second group (20%, 31.6% and 20%, respectively). In conclusion, in patients who still have symptoms on treatment with inhaled corticosteroids, the addition of a long-acting beta2-agonist, leukotriene antagonists or sustained-release theophylline to the treatment is a logical approach, and, in addition to inhaled corticosteroids, any one of these second controller medications may be chosen in patients with moderate asthma.

CD001281

Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

CD001281

Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

Inhaled salmeterol or oral theophylline in nocturnal asthma?

Nocturnal cough and wheeze are common in asthma and often treated with beta2 agonists or theophyllines. As nocturnal asthma and these therapies may affect sleep and cognition, we compared 50 microg salmeterol inhaled every 12 h with individually dose-titrated sustained-release oral theophylline on sleep quality and cognitive performance in 15 patients with stable nocturnal asthma (overnight peak expiratory flow rate [PEFR] fall > or = 15%, > or = 1 asthmatic awakening/week) using a double-blind, double-dummy, crossover design with 14-d therapy limbs. Cognitive testing and polysomnography were performed on Nights 13 and 14. Trough plasma theophylline concentration after Night 14 on theophylline was median 11.1 (interquartile range 8.3, 15.2) microg/ml. Overnight PEFR falls were similar [salmeterol 2.3 (0, 10.6), theophylline 3.5 (-0.3, 9.6)%, p = 0.4] but on salmeterol there were more nights without awakenings [median difference 1 (0, 2), p < 0.01], fewer nocturnal arousals [difference -3 (-7, 2) h(-1), p < 0.05] and improved quality of life (p = 0.05). Sleep architecture did not otherwise differ. Visual vigilance improved on salmetrol (p < 0.05), but otherwise daytime cognition was unaffected. There was no patient preference for either therapy. Hence in patients with nocturnal asthma, we demonstrate no major clinical advantage, but a small benefit in sleep quality, quality of life, and daytime cognitive function with salmeterol.

CD001281

Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

Long-term treatment of asthmatic patients with salmeterol vs slow-release theophylline.

The aim of the present multicentre, open, randomized, parallel group study was to evaluate the efficacy and safety of salmeterol versus theophylline in asthmatic patients. A total of 112 patients were randomized: 56 received inhaled salmeterol (50 micrograms twice daily) and 50 oral dose titrated theophylline twice daily. The study lasted 12 months. The efficacy of both drugs was evaluated for the first 3 months of the study and the safety for a further 9 months. Spirometric measurements were carried out for the total duration of the study. Salmeterol showed a greater and more significant efficacy than theophylline in reducing both day- and night-time symptoms (P < 0.001) and in reducing additional salbutamol requirement (P < 0.001). The subjective assessment of efficacy by physicians and patients was in favour of salmeterol from the first month of treatment (P < 0.001). Both drugs improved the quality of life as measured by the specific questionnaire 'Living with Asthma' with no significant differences. The total number of adverse events was slightly higher in the theophylline group compared with salmeterol (18 vs 9; P n.s.). Both salmeterol and theophylline increased morning and evening PEFR with no significant difference. FEV1 and FVC increased in both groups of patients; the difference between the effects of the two treatment was not statistically significant at 12 months. Our study suggests that salmeterol has higher efficacy and safety than theophylline in long-term treatment of asthmatic patients.

CD001281

Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

The efficacy and tolerability of inhaled salmeterol and individually dose-titrated, sustained-release theophylline in patients with reversible airways disease.

In a double-blind, double-dummy, cross-over, multicentre study, 141 patients with moderate reversible airways disease were randomized to receive either 50 micrograms salmeterol via a metered dose inhaler or individually dose-titrated oral theophylline, both twice daily for a 2-week period. Just over half (n = 77) the patients had received theophylline before, but 64 patients were new to theophylline therapy. Efficacy was based on lung function data and symptom scores. Salmeterol produced significantly higher increase in mean morning peak expiratory flow (PEF) of 161 min-1 (P < 0.001; 95% Confidence Interval (CI); 8-241 min-1) and mean evening PEF of 151 min-1 (p < 0.001; 95% CI; 7-221 min-1) compared with theophylline therapy. Further analysis of the data revealed that the increase in PEF with salmeterol compared with theophylline was highest in a sub-group of patients new to theophylline therapy. Patients on salmeterol had significantly less night-time awakenings than those on theophylline (P = 0.011) and significantly less daytime symptoms (P = 0.017). There was also a significant increase in the number of nights (P = 0.013) and days (P < 0.001) on salmeterol when no additional salbutamol was required compared with theophylline. Theophylline produced a higher incidence of adverse events compared with salmeterol. The results of this study show that inhaled salmeterol is more effective and better tolerated than individually dose-titrated oral theophylline over a 2-week study period in patients with moderate asthma.

CD001281

Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

[Therapy of nocturnal asthma: salmeterol versus nocturnal administration of retard theophylline--comparison of effectiveness and tolerance].

The aim of the present study was to compare the efficacy and the tolerability of salmeterol and theophylline in patients with nocturnal asthma. 16 patients were entered into a randomized, double-blind, crossover trial. Using a double-dummy technique, salmeterol (50 micrograms b.i.d. by MDI) or theophylline (Uniphyllin; 600 mg nocte orally) were given for periods of 7 days with a wash-out period of 7 days between treatment periods. With salmeterol the number of nights with an overnight fall in peak expiratory peak flow rate (PEFR) of at least 20% was reduced by about 20% compared to about 10% with theophyllin (p < 0.05 for the difference between salmeterol and theophylline). With respect to nocturnal symptoms 62.6% of the patients had rare or non symptoms without and 84.7% with salmeterol, compared to 46.5% without and 67.3% with theophylline (p < 0.05). With respect to the improvement of early morning symptoms, the increase of nights with none or rare symptoms was 46.2% with salmeterol compared to 25.8% with theophylline. The overall parameter of efficacy defined as a) the number of nights with an overnight fall in PEFR or less than 20% als well as b) none or rare nocturnal symptoms and c) none or rare early morning symptoms increased from 23.4% at baseline to 75.1% during treatment with salmeterol compared to an increase from 24.5% at baseline with 54.8% during treatment with theophylline (p < 0.05). 12 patients preferred salmeterol over theophylline (p < 0.05). 3 patients had gastrointestinal disturbances during theophylline treatment. It can be concluded that both salmeterol and theophylline are effective in the treatment of nocturnal asthma. With respect to the overall efficacy and the tolerability salmeterol is superior to theophylline.

CD001545

Chemotherapy is effective in prolonging time to disease progression and survival in patients with advanced colorectal cancer. The survival benefit may be underestimated by this meta-analysis, as a proportion of patients in the control arms of some trials received chemotherapy. No age related differences were found in the effectiveness of chemotherapy, but elderly patients were under represented in trials. Treatment toxicity and impact upon quality of life and symptom control have been inadequately assessed in the majority of trials and further research is needed to clarify the palliative benefit of chemotherapy.

Two phase III trials of tauromustine (TCNU) in advanced colorectal cancer.

CD001545

Chemotherapy is effective in prolonging time to disease progression and survival in patients with advanced colorectal cancer. The survival benefit may be underestimated by this meta-analysis, as a proportion of patients in the control arms of some trials received chemotherapy. No age related differences were found in the effectiveness of chemotherapy, but elderly patients were under represented in trials. Treatment toxicity and impact upon quality of life and symptom control have been inadequately assessed in the majority of trials and further research is needed to clarify the palliative benefit of chemotherapy.

Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases.

Very few patients with liver metastases from colorectal cancer can be cured. We have investigated whether a treatment to slow the growth of liver metastases, hepatic-artery infusion of floxuridine, improves palliation in this setting. In a randomised study of 100 patients, we compared quality of life and survival in patients who received hepatic-artery infusion of floxuridine and in those who received conventional symptom palliation. 95% of control patient survival time was spent with normal quality-of-life scores, which suggests that the aim of treatment should be to prolong normal-quality survival rather than merely to sustain quality of life. There was a significant prolongation (p = 0.03) in overall survival in floxuridine-treated patients compared with controls (median 405 vs 226 days). There were similar significant prolongations in normal-quality (ie, normal symptom scores) survival for physical symptoms (p = 0.04), anxiety (p = 0.04), and depression (p = 0.04). This survival benefit was associated with significant reductions in metastasis size on computed tomography (p = 0.001) and in serum carcinoembryonic antigen concentration (p = 0.006) in floxuridine-treated patients. There was no evidence of treatment-related hepatotoxicity as assessed by serum aspartate aminotransferase and bilirubin measurements. This is the first demonstration that survival can be prolonged with normal quality of life in patients with colorectal liver metastases. We conclude that hepatic-artery floxuridine infusion can be recommended for suitable patients.

CD001545

Chemotherapy is effective in prolonging time to disease progression and survival in patients with advanced colorectal cancer. The survival benefit may be underestimated by this meta-analysis, as a proportion of patients in the control arms of some trials received chemotherapy. No age related differences were found in the effectiveness of chemotherapy, but elderly patients were under represented in trials. Treatment toxicity and impact upon quality of life and symptom control have been inadequately assessed in the majority of trials and further research is needed to clarify the palliative benefit of chemotherapy.

General condition of asymptomatic patients with advanced colorectal cancer receiving palliative chemotherapy. A longitudinal study.

A Nordic multicenter study in asymptomatic patients with advanced colorectal cancer compared initial chemotherapy with sequential methotrexate-5-FU with leucovorin rescue (MFL) for 6 months versus primary expectancy with chemotherapy only after the appearance of symptoms. The study (183 patients randomized between January 1985 and February 1990) showed that symptom-free survival, progression-free survival and survival respectively were about 6 months longer in the group of patients randomized to initial MFL. Whether these prolongations could be achieved without an impaired 'quality of life' was studied in an associated study. Between January 1985 and March 1987, 43 patients were randomized at one of the hospitals, 36 of which were interviewed with a questionnaire at randomization. Even if all these patients were considered, by the physician, to be 'free of symptoms from their disease', 16/36 (44%) had symptoms that could be referred to the disease. In spite of this, the patients were in a good general condition, and considerably better off than patients considered to have 'symptoms from the disease' who were interviewed with the same questionnaire when randomized in a parallel study of symptomatic patients. Patients randomized to initial chemotherapy and interviewed longitudinally maintained their good condition throughout treatment. Toxicity was mild, although the patients expressed more adverse effects than the physicians recorded. Since symptom-free survival, progression-free survival and survival were statistically significantly longer in the group of patients randomized to MFL also in this associated study, it is concluded that initial chemotherapy can prolong symptom-free survival and survival without reduced 'quality of life' during the treatment period.

CD001545

Chemotherapy is effective in prolonging time to disease progression and survival in patients with advanced colorectal cancer. The survival benefit may be underestimated by this meta-analysis, as a proportion of patients in the control arms of some trials received chemotherapy. No age related differences were found in the effectiveness of chemotherapy, but elderly patients were under represented in trials. Treatment toxicity and impact upon quality of life and symptom control have been inadequately assessed in the majority of trials and further research is needed to clarify the palliative benefit of chemotherapy.

Cost-effectiveness of palliative chemotherapy in advanced gastrointestinal cancer.

Chemotherapy may relieve tumor-related symptoms, may improve quality of life and prolong survival in advanced gastrointestinal cancer. The extent of such improvements is unclear despite the extensive use of this treatment modality, and there are no studies concerning the economic cost of any gain achieved in the quantity and quality of life by chemotherapy. Between January 1991 and May 1992, 61 patients with inoperable cancer (18 gastric, 22 pancreatic or biliary, and 21 colorectal) were randomized to either primary chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not achieve palliation. All economic costs for medical care were prospectively recorded, and marginal cost-effectiveness analyses were performed. More patients in the primary chemotherapy group (19/33, 58%) had improved/prolonged high quality of life (QoL-patient, minimum duration 4 months) than in the best supportive care group (8/28, 29%, p < 0.05). Overall survival and quality-adjusted survival were significantly longer in the primary chemotherapy group (median 9 vs. 4 months, p < 0.05), and median 7 vs. 2 months, p < 0.05, respectively). When analysed by cancer site, survival was significantly prolonged in gastric cancer patients (median 10 vs. 4 months, p < 0.02), but not in colorectal (median 12 vs. 6 months, p = 0.1) and pancreatic-biliary cancer patients (median 8 vs. 5 months, p = 0.8). The average cost for all medical care was approximately 50% higher in the primary chemotherapy group, but the average cost per day was the same in the two groups. Hospitalization accounted for most of the costs in both groups. The incremental costs per gained year of life was SEK 166,400 ($21,300), per gained quality-adjusted year of life SEK 157,200 ($20,200), and per QoL-patient SEK 160,300 ($20,600). These costs were lower for gastric and colorectal cancer patients, and much higher for pancreatic-biliary cancer patients. The results of this study suggest that palliative chemotherapy is cost-effective in patients with advanced gastric and colorectal cancer. Knowledge about survival and quality of life benefits is still limited in patients suffering from gastric and pancreatic-biliary cancer.

CD001545

Chemotherapy is effective in prolonging time to disease progression and survival in patients with advanced colorectal cancer. The survival benefit may be underestimated by this meta-analysis, as a proportion of patients in the control arms of some trials received chemotherapy. No age related differences were found in the effectiveness of chemotherapy, but elderly patients were under represented in trials. Treatment toxicity and impact upon quality of life and symptom control have been inadequately assessed in the majority of trials and further research is needed to clarify the palliative benefit of chemotherapy.

Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial.

Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer. Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations. The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month). This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials.

CD005291

PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure. Trials in which PGS was offered to women with a good prognosis suggested similar outcomes. PGS technique development is still ongoing in an effort to increase its efficacy. This involves biopsy at other stages of development (polar body or trophectoderm biopsy) and other methods of analysis (comparative genome hybridisation (CGH) or array-based technologies) than used by the trials included in this review. These new developments should be properly evaluated before their routine clinical application. Until such trials have been performed, PGS should not be offered as routine patient care in any form.

Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial.

It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate. Therefore, advanced maternal age (AMA) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) on the outcome after assisted reproductive technology (ART). A prospective randomized controlled clinical trial (RCT) was carried out comparing the outcome after blastocyst transfer combined with PGD-AS using fluorescence in situ hybridization (FISH) for the chromosomes X, Y, 13, 16, 18, 21 and 22 in AMA couples (aged > or =37 years) with a control group without PGD-AS. From the 400 (200 for PGD-AS and 200 controls) couples that were allocated to the trial, an oocyte pick-up was performed effectively in 289 cycles (148 PGD-AS cycles and 141 control cycles). Positive serum HCG rates per transfer and per cycle were the same for PGD-AS and controls: 35.8% (19.6%) [%/per embryo transfer (per cycle)] and 32.2% (27.7%), respectively (NS). Significantly fewer embryos were transferred in the PGD-AS group than in the control group (P<0.001). The implantation rate (with fetal heart beat) was 17.1% in the PGD-AS group versus 11.5% in the control group (not significant; P=0.09). We observed a normal diploid status in 36.8% of the embryos. This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred.

CD005291

PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure. Trials in which PGS was offered to women with a good prognosis suggested similar outcomes. PGS technique development is still ongoing in an effort to increase its efficacy. This involves biopsy at other stages of development (polar body or trophectoderm biopsy) and other methods of analysis (comparative genome hybridisation (CGH) or array-based technologies) than used by the trials included in this review. These new developments should be properly evaluated before their routine clinical application. Until such trials have been performed, PGS should not be offered as routine patient care in any form.

Prospectively randomized controlled trial of PGS in IVF/ICSI patients with poor implantation.

This randomized, controlled trial verifies whether patients with recurrent failed implantation benefit from preimplantation genetic diagnosis for aneuploidy, as compared with conventional assisted reproduction treatment procedures. Two hundred patients with recurrent failed implantation were randomized into two groups. A total of 139 patients underwent ovarian stimulation, and preimplantation genetic screening was performed in 72 patients. Analysis of chromosomes X, Y, 13, 16, 18, 21 and 22 was carried out using fluorescence in-situ hybridization in blastomeres of day-3 cleavage-stage embryos in the study group. The primary endpoint was implantation rate. Secondary endpoints were embryonic morphology and chromosomal status, number of transferred embryos and clinical pregnancy rate. With regard to the implantation rate, there was no significant difference between the study group (21.4%) and the control group (25.3%). The number of embryos transferred was significantly lower in the study group, namely 1.4 (SD 1.0) versus 2.1 (SD 1.0) in the control group (P < 0.05). The clinical pregnancy rate was not significantly different between the groups (25.0% in the study group versus 40.3% in the control group). It can be concluded that preimplantation genetic screening does not increase the implantation rates after IVF-intracytoplasmic sperm injection in women with repeated implantation failure.

CD005291

PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure. Trials in which PGS was offered to women with a good prognosis suggested similar outcomes. PGS technique development is still ongoing in an effort to increase its efficacy. This involves biopsy at other stages of development (polar body or trophectoderm biopsy) and other methods of analysis (comparative genome hybridisation (CGH) or array-based technologies) than used by the trials included in this review. These new developments should be properly evaluated before their routine clinical application. Until such trials have been performed, PGS should not be offered as routine patient care in any form.

Preimplantation genetic screening in women of advanced maternal age caused a decrease in clinical pregnancy rate: a randomized controlled trial.

Advanced maternal age (AMA) is an important parameter that negatively influences the clinical pregnancy rate in IVF, in particular owing to the increased embryo aneuploidy rate. It has thus been suggested that only transferring euploid embryos in this patient group would improve the pregnancy rate. The purpose of this study was to test whether employing preimplantation genetic screening (PGS) in AMA patients would increase the clinical pregnancy rate. We conducted a two-center, randomized controlled trial (RCT) to analyze the outcome of embryo transfers in AMA patients (>or=38 years of age) after PGS using FISH analysis for chromosomes X, Y, 13, 16, 18, 21 and 22. The PGS group was compared with a control group. The primary outcome measure was clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. The study was terminated early as an interim analysis showed a very low conditional power of superiority for the primary outcome. Of the 320 patients calculated to be included in the study, 56 and 53 patients were randomized into the PGS and control groups, respectively. The clinical pregnancy rate in the PGS group was 8.9% (95% CI, 2.9-19.6%) compared with 24.5% (95% CI, 13.8-38.3%) in the control group, giving a difference of 15.6% (95% CI, 1.8-29.4%, P = 0.039). Although the study was terminated early, this RCT study provides evidence against the use of PGS for AMA patients when performing IVF. Trial registration number: ISRCTN38014610.

CD005291

PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure. Trials in which PGS was offered to women with a good prognosis suggested similar outcomes. PGS technique development is still ongoing in an effort to increase its efficacy. This involves biopsy at other stages of development (polar body or trophectoderm biopsy) and other methods of analysis (comparative genome hybridisation (CGH) or array-based technologies) than used by the trials included in this review. These new developments should be properly evaluated before their routine clinical application. Until such trials have been performed, PGS should not be offered as routine patient care in any form.

Preimplantation aneuploidy testing for infertile patients of advanced maternal age: a randomized prospective trial.

To assess the potential benefit of preimplantation aneuploidy testing on the outcome of in vitro fertilization (IVF) for women of advanced maternal age (AMA). Prospective randomized clinical trial. Private IVF clinic. Sixty-two infertile AMA couples undergoing fertility treatment. Fluorescent in situ hybridization (FISH) for chromosomes X, Y, 13, 15, 16, 17, 18, 21, and 22. Preimplantation aneuploidy testing of biopsied blastomeres on day 3 of development. Fertilization and blastocyst developmental rates were similar for the test and control groups: 80% versus 77.4% and 49% versus 48.2%, respectively. The average number of embryos transferred was comparable at 2.2 for the test group and 2.7 for the control group. Implantation rates were also equivalent across the two groups: 37.3% in the control group versus 36.5% in the test group. Nevertheless, the spontaneous abortion rate was observed to be lower for the test group: 25.9% versus 32.26% in the control group. This resulted in an observed increase in delivery rates for the test group: 78% versus 67.74% in the control group. Preimplantation aneuploidy testing does not appear to statistically significantly improve outcome parameters in infertile AMA patients; however, a trend toward a decrease in the spontaneous abortion rate with a subsequent higher delivery rate was observed.

CD005291

PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure. Trials in which PGS was offered to women with a good prognosis suggested similar outcomes. PGS technique development is still ongoing in an effort to increase its efficacy. This involves biopsy at other stages of development (polar body or trophectoderm biopsy) and other methods of analysis (comparative genome hybridisation (CGH) or array-based technologies) than used by the trials included in this review. These new developments should be properly evaluated before their routine clinical application. Until such trials have been performed, PGS should not be offered as routine patient care in any form.

Preimplantation genetic screening does not improve delivery rate in women under the age of 36 following single-embryo transfer.

Single-embryo transfer is a well-accepted strategy to avoid multiple pregnancies in an assisted reproductive technology (ART) programme. Besides the morphological quality and embryo kinetics up to the blastocyst stage, preimplantation genetic screening (PGS) of aneuploidy has been advocated as an adjuvant approach to select the embryo. Couples with a female partner younger than 36 were randomly assigned to undergo transfer of a single blastocyst in a cycle with or without PGS using FISH for the chromosomes X, Y, 13, 16, 18, 21, 22. After the enrolment of 120 of the projected 447 patients in each group, study recruitment was terminated prematurely on the basis of futility. The observed live birth delivery rates after ART were 30.8 versus 30.8% per randomized patient, 34.6 versus 34.6% per cycle initiated, 37.8 versus 37.0% per aspirated cycle and 41.6 versus 43.5% per embryo transfer for the control versus the PGS group, respectively, with absolute between-group differences (95% CI; P value) of 0% (-11.7 to 11.7; P = 1.00), 0% (-12.7 to 12.7; P = 1.00), -0.8% (-14.2 to 12.7; P = 0.91) and 2.1% (-12.7 to 16.7; P = 0.79), respectively. Even in this younger age group, only 61% of the embryos had a normal diploid status. The absence of a beneficial treatment effect in this randomized clinical trial provides no arguments in favour of PGS to improve live birth delivery rate following single-embryo transfer in women under the age 36. Clinical Trials.gov: NCT00670059.

CD005291

PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure. Trials in which PGS was offered to women with a good prognosis suggested similar outcomes. PGS technique development is still ongoing in an effort to increase its efficacy. This involves biopsy at other stages of development (polar body or trophectoderm biopsy) and other methods of analysis (comparative genome hybridisation (CGH) or array-based technologies) than used by the trials included in this review. These new developments should be properly evaluated before their routine clinical application. Until such trials have been performed, PGS should not be offered as routine patient care in any form.

What next for preimplantation genetic screening (PGS)? Experience with blastocyst biopsy and testing for aneuploidy.

Blastocysts more commonly have a normal karyotype than cleavage-stage embryos do. Moreover, blastocysts have also made a metabolic transition from catabolism and recycling of the oocyte's reserves and resources, processes that fuel the first 3 days of cleavage. Although not all blastocysts are karyotypically equal, it is still to be determined to what extent a mosaic karyotype might be a normal feature among embryos, both at the cleavage stage and the blastocyst stage--and when looking for karyotypic abnormalities by embryo biopsy might help the chance of implantation rather than harm it. It is also still impractical to look at all the chromosomes that can, through their aneuploidy, stand in the way of successful embryonic and fetal development. We report a randomized clinical trial of blastocyst biopsy followed by preimplantation genetic screening (PGS) for aneuploidy using 5-colour FISH. The trial was suspended and then terminated early when we were unable to show an advantage for PGS. If we are correct in assuming that mitotic non-disjunction is common by the stage of the blastocyst (and that it is much less ominous than meiotic non-disjunction), then further studies of effective PGS of blastocysts for aneuploidy require methods of analysis that cover all the chromosomes and can differentiate the triallelic and monoallelic states of meiotically derived aneuploidies from the biallelic state of mitotic aneuploidies.

CD005291

PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure. Trials in which PGS was offered to women with a good prognosis suggested similar outcomes. PGS technique development is still ongoing in an effort to increase its efficacy. This involves biopsy at other stages of development (polar body or trophectoderm biopsy) and other methods of analysis (comparative genome hybridisation (CGH) or array-based technologies) than used by the trials included in this review. These new developments should be properly evaluated before their routine clinical application. Until such trials have been performed, PGS should not be offered as routine patient care in any form.

Preimplantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at least 35 years: a prospective randomized trial.

To test the hypothesis that patients with advanced maternal age (AMA) have a higher implantation rate (IR) after embryo transfer of embryos with a normal chromosomal pattern for the chromosomes studied with preimplantation genetic screening (PGS) compared with patients who had an embryo transfer without PGS. Prospective randomized controlled trial (RCT). Academic tertiary setting. Patients with AMA (> or =35 years). In an RCT, the clinical IR per embryo transferred was compared after embryo transfer on day 5 or 6 between the PGS group (analysis of chromosomes 13, 16, 18, 21, 22, X, and Y) and the Control group without PGS. No differences were observed between the PGS group and the Control group for the clinical IR (15.1%; 14.9%; rate ratio 1.01; exact confidence interval [CI], 0.25-5.27), the ongoing IR (at 12 weeks) (9.4%; 14.9%), and the live born rate per embryo transferred (9.4%; 14.9%; rate ratio 0.63; exact CI, 0.08-3.37). Fewer embryos were transferred in the PGS group (1.6 +/- 0.6) than in the Control group (2.0 +/- 0.6). A normal diploid status was observed in 30.3% of the embryos screened by PGS. In this RCT, the results did not confirm the hypothesis that PGS results in improved reproductive outcome in patients with AMA. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

CD005291

PGS as currently performed significantly decreases live birth rates in women of advanced maternal age and those with repeated IVF failure. Trials in which PGS was offered to women with a good prognosis suggested similar outcomes. PGS technique development is still ongoing in an effort to increase its efficacy. This involves biopsy at other stages of development (polar body or trophectoderm biopsy) and other methods of analysis (comparative genome hybridisation (CGH) or array-based technologies) than used by the trials included in this review. These new developments should be properly evaluated before their routine clinical application. Until such trials have been performed, PGS should not be offered as routine patient care in any form.

A prospective randomized controlled trial of preimplantation genetic screening in the "good prognosis" patient.

To determine whether the routine use of preimplantation genetic screening (PGS) in "good prognosis" women improves in vitro fertilization (IVF) cycle outcome. Randomized, controlled, prospective clinical study. Private infertility clinic. Infertile women predicted to have a good prognosis as defined by: age <39 years, normal ovarian reserve, body mass index <30 kg/m(2), presence of ejaculated sperm, normal uterus, <or=2 previous failed IVF cycles. Patients were randomized to the PGS group or the control group on day 3 after oocyte retrieval; 23 women underwent blastomere biopsy on day 3 after fertilization (PGS group), and 24 women underwent routine IVF (control group). All embryos were transferred on day 5 or 6 after fertilization. Pregnancy, implantation, multiple gestation, and live birth rates. No statistically significant differences were found between the PGS and control groups with respect to clinical pregnancy rate (52.4% versus 72.7%). However, the embryo implantation rate was statistically significantly lower for the PGS group (31.7% versus 62.3%) as were the live birth rate (28.6% versus 68.2%) and the multiple birth rate (9.1% versus 46.7%). In a "good prognosis" population of women, PGS does not appear to improve pregnancy, implantation, or live birth rates.

CD006921

The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical (benefits and adverse events), radiological or pharmacological outcomes. Based on the evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses.

Methylprednisolone in multiple sclerosis: a comparison of oral with intravenous therapy at equivalent high dose.

A randomised double-blind placebo-controlled trial of intravenous methylprednisolone versus oral methylprednisolone at equivalent high dose was carried out on 35 patients with an acute relapse of multiple sclerosis (MS). After baseline evaluation each was randomly allocated to oral treatment and intravenous placebo or intravenous treatment and oral placebo, receiving 500 mg of methylprednisolone for five consecutive days and with reassessment at days five and twenty-eight. There was no significant difference in response when disability or functional scores were compared in the two groups. Adverse effects were minor and equally distributed. In this study oral treatment with methylprednisolone was as effective as intravenous treatment in acute relapse of MS.

CD006921

The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical (benefits and adverse events), radiological or pharmacological outcomes. Based on the evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses.

The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis.

Oral prednisone (1)might be a convenient, inexpensive alternative to IV methylprednisolone (IVMP) if the bioequivalent dose was known. We compared the total amount of steroid absorbed after 1250 mg oral prednisone vs 1 gram IVMP in 16 patients with multiple sclerosis (MS). At 24 hours, the mean area under the concentration-time curve (AUC), the main component of bioavailability, did not differ between groups (p = 0.122). This suggests that the amount of absorbed corticosteroid is similar after either steroid at these doses.

CD006921

The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical (benefits and adverse events), radiological or pharmacological outcomes. Based on the evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses.

Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis.

An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis (MS) despite the lack of evidence to support this route of administration. Our double-blind placebo-controlled randomised trial was designed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS. 42 patients with clinically definite relapse in MS received oral, and 38 intravenous, methylprednisolone. Clinical measurements at entry and at 1 week, 4 weeks, 12 weeks, and 24 weeks included Kurtzke's expanded disability status scale (EDSS), Hauser's Ambulatory Index, and an arm-function index. The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grades at 4 weeks. There were no significant differences between the two groups at any stage of the study in any measurement taken: the mean difference in EDSS at 4 weeks (adjusted for baseline level) was 0.07 grades more in those taking oral steroids (95% CI -0.46 to 0.60). The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment. Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience, safety, and cost.

CD006921

The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical (benefits and adverse events), radiological or pharmacological outcomes. Based on the evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses.

A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS.

To compare the efficacy, tolerability, and safety of IV methylprednisolone (IV MP) vs oral methylprednisolone (oMP) at equivalent high doses in patients with multiple sclerosis (MS) experiencing a recent relapse. Patients with a clinical relapse within the previous 2 weeks and at least 1 gadolinium (Gd)-enhancing lesion on a screening brain MRI scan were included. Forty patients with MS were randomized to receive either 1 g/day for 5 days of oMP (20 patients) or 1 g/day for 5 days of IV MP (20 patients). Expanded Disability Status Scale (EDSS) and brain MRI (dual-echo and postcontrast T1-weighted scans) were assessed at baseline and at weeks 1 and 4. The study primary research question (endpoint) was to compare the efficacy of the 2 treatment routes in reducing the number of Gd-enhancing lesions after 1 week from treatment initiation. Secondary outcomes were safety, tolerability, and clinical efficacy profiles of the 2 routes of administration. The 2 groups showed a reduction of Gd-enhancing lesions over time (p = 0.002 for oMP and p = 0.001 for IV MP) with a "non-inferiority effect" between the 2 routes of administration at week 1. Both groups showed an improvement of EDSS over time (p < 0.001) without between-group difference at week 4. Both treatments were well-tolerated and adverse events were minimal and occurred similarly in the 2 treatment arms. Oral methylprednisolone (oMP) is as effective as IV methylprednisolone in reducing gadolinium-enhancing lesions in patients with MS soon after an acute relapse with similar clinical, safety, and tolerability profiles. This study provides class III evidence that 1 g oMP x 5 days is not inferior to 1 g IV MP x 5 days in reducing the number of gadolinium-enhancing lesions over a period of 1 week (mean difference in lesion reduction comparing IV MP to oMP is -20%, 95% confidence interval -48% to + 5%).

CD008914

This systematic review suggests that the use of external stents following pancreaticoduodenectomy may be beneficial. However, only a limited number of RCTs with rather small sample sizes were available. Further RCTs on the use of stents after pancreaticoduodenectomy are warranted.

External pancreatic duct stent decreases pancreatic fistula rate after pancreaticoduodenectomy: prospective multicenter randomized trial.

Pancreatic fistula (PF) is a leading cause of morbidity and mortality after pancreaticoduodenectomy (PD). The aim of this multicenter prospective randomized trial was to compare the results of PD with an external drainage stent versus no stent. Between 2006 and 2009, 158 patients who underwent PD were randomized intraoperatively to either receive an external stent inserted across the anastomosis to drain the pancreatic duct (n = 77) or no stent (n = 81). The criteria of inclusion were soft pancreas and a diameter of wirsung <3 mm. The primary study end point was PF rate defined as amylase-rich fluid (amylase concentration >3 times the upper limit of normal serum amylase level) collected from the peripancreatic drains after postoperative day 3. CT scan was routinely done on day 7. The 2 groups were comparable concerning demographic data, underlying pathologies, presenting symptoms, presence of comorbid illness, and proportion of patients with preoperative biliary drainage. Mortality, morbidity, and PF rates were 3.8%, 51.8%, and 34.2%, respectively. Stented group had a significantly lower overall PF (26% vs. 42%; P = 0.034), morbidity (41.5% vs. 61.7%; P = 0.01), and delayed gastric emptying (7.8% vs. 27.2%; P = 0.001) rates compared with nonstented group. Radiologic or surgical intervention for PF was required in 9 patients in the stented group and 12 patients in the nonstented group. There were no significant differences in mortality rate (3.7% vs. 3.9%; P = 0.37) and in hospital stay (22 days vs. 26 days; P = 0.11). External drainage of pancreatic duct with a stent reduced. PF and overall morbidity rates after PD in high risk patients (soft pancreatic texture and a nondilated pancreatic duct). (C) 2011 Lippincott Williams & Wilkins, Inc.

CD008914

This systematic review suggests that the use of external stents following pancreaticoduodenectomy may be beneficial. However, only a limited number of RCTs with rather small sample sizes were available. Further RCTs on the use of stents after pancreaticoduodenectomy are warranted.

External drainage of pancreatic duct with a stent to reduce leakage rate of pancreaticojejunostomy after pancreaticoduodenectomy: a prospective randomized trial.

Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy. External drainage of pancreatic duct with a stent has been shown to reduce pancreatic fistula rate of pancreaticojejunostomy in a few retrospective or prospective nonrandomized studies, but no randomized controlled trial has been reported thus far. This single-center prospective randomized trial compared the results of pancreaticoduodenectomy with external drainage stent versus no stent for pancreaticojejunal anastomosis. A total of 120 patients undergoing pancreaticoduodenectomy with end-to-side pancreaticojejunal anastomosis were randomized to have either an external stent inserted across the anastomosis to drain the pancreatic duct (n = 60) or no stent (n = 60). Duct-to-mucosa anastomosis was performed in all cases. The 2 groups were comparable in demographic data, underlying pathologies, pancreatic consistency, and duct diameter. Stented group had a significantly lower pancreatic fistula rate compared with nonstented group (6.7% vs. 20%, P = 0.032). Radiologic or surgical intervention for pancreatic fistula was required in 1 patient in the stented group and 4 patients in the nonstented group. There were no significant differences in overall morbidity (31.7% vs. 38.3%, P = 0.444) and hospital mortality (1.7% vs. 5%, P = 0.309). Two patients in the nonstented group and none in the stented group died of pancreatic fistula. Hospital stay was significantly shorter in the stented group (mean 17 vs. 23 days, P = 0.039). On multivariate analysis, no stenting and pancreatic duct diameter <3 mm were significant risk factors of pancreatic fistula. External drainage of pancreatic duct with a stent reduced leakage rate of pancreaticojejunostomy after pancreaticoduodenectomy.

CD008914

This systematic review suggests that the use of external stents following pancreaticoduodenectomy may be beneficial. However, only a limited number of RCTs with rather small sample sizes were available. Further RCTs on the use of stents after pancreaticoduodenectomy are warranted.

Usefulness of performing a pancreaticojejunostomy with an internal stent after a pancreatoduodenectomy.

In pancreaticojejunostomy (PJ), the occurrence of an injury during the removal of a stented tube is sometimes related to pancreatitis or late-onset stenosis of the pancreatic duct. In this study, we compare the outcomes of a PJ with an external stent versus an internal stent in a randomized study. We compared the complications including pancreatic fistula, mortality, and postoperative hospital stay of 43 patients who had PJ with an external stent (group E) or PJ with an internal stent (group I) after a pancreaticoduodenectomy (PD). Pancreatic fistula occurred in 8 patients (36.4%) in group E, while it only was seen in 7 patients (33.3%) in group I. Pancreatitis was recognized in 3 patients in group E, while there was no patient in whom an obstruction due to an internal stent was suspected. Pancreaticojejunostomy with an internal stent is therefore considered to be an effective treatment alternative after PD, with an acceptable morbidity and no mortality.

CD008914

This systematic review suggests that the use of external stents following pancreaticoduodenectomy may be beneficial. However, only a limited number of RCTs with rather small sample sizes were available. Further RCTs on the use of stents after pancreaticoduodenectomy are warranted.

Does pancreatic duct stenting decrease the rate of pancreatic fistula following pancreaticoduodenectomy? Results of a prospective randomized trial.

Pancreatic duct stenting remains an attractive strategy to reduce the incidence of pancreatic fistulas following pancreaticoduodenectomy (PD) with encouraging results in both retrospective and prospective studies. We performed a prospective randomized trial to test the hypothesis that internal pancreatic duct stenting reduces the development of pancreatic fistulas following PD. Two hundred thirty-eight patients were randomized to either receive a pancreatic stent (S) or no stent (NS), and stratified according to the texture of the pancreatic remnant (soft/normal versus hard). Four patients were excluded from the study; in three instances due to a pancreatic duct that was too small to cannulate and in the other instance because a total pancreatectomy was performed. Patients who randomized to the S group had a 6-cm-long segment of a plastic pediatric feeding tube used to stent the pancreaticojejunostomy anastomosis. In patients with a soft pancreas, 57 randomized to the S group and 56 randomized to the NS group. In patients with a hard pancreas, 58 randomized to the S group and 63 randomized to the NS group. The S and NS groups for the entire study population, as well as for the subgroup of high-risk patients with soft pancreata, were similar as regard to demographics, past medical history, preoperative symptoms, preoperative procedures, and intraoperative data. The pancreatic fistula rate for the entire study population was 9.4%. The fistula rates in the S and NS subgroups with hard pancreata were similar, at 1.7% and 4.8% (P = 0.4), respectively. The fistula rates in the S and NS subgroups with soft pancreata were also similar, at 21.1% and 10.7% (P = 0.1), respectively. A nonstatistically significant increase in the pancreatic fistula rate in the S group persisted after adjusting for the operating surgeon and technical details of the operation (e.g., anastomotic technique, anastomotic orientation, pancreatic duct size, and number of intra-abdominal drains placed). In patients with soft pancreata, 63% percent of the pancreatic fistulas in stented patients required adjustment to the clinical pathway (including two deaths), compared to 47% of the pancreatic fistulas in patients in the NS group (P = 0.3). Internal pancreatic duct stenting does not decrease the frequency or the severity of postoperative pancreatic fistulas.

CD008914

This systematic review suggests that the use of external stents following pancreaticoduodenectomy may be beneficial. However, only a limited number of RCTs with rather small sample sizes were available. Further RCTs on the use of stents after pancreaticoduodenectomy are warranted.

A prospective randomized controlled trial of internal versus external drainage with pancreaticojejunostomy for pancreaticoduodenectomy.

A stent often is placed across the pancreaticojejunostomy. However, there is no report compared between internal drainage and external drainage. We conducted a prospective randomized trial (NCT00628186 registered at http://ClinicalTrials.gov) with 100 patients who underwent pancreaticoduodenectomy and we compared the effects on postoperative course. The incidence of pancreatic fistula according to the International Study Group on Pancreatic Fistula criteria was not different (external, 20%; vs internal, 26%), and the incidence of the other complications was similar between stent types. The median postoperative hospital stay was 21 days (range, 8-163 d) in the internal drainage group, which was shorter than the median stay of 24 days (range, 21-88 d) in the external drainage group (P = .016). Both internal drainage and external drainage were safety devices for pancreaticojejunostomy. Internal drainage simplifies postoperative managements and it might shorten postoperative stay for pancreaticoduodenectomy. Copyright 2010 Elsevier Inc. All rights reserved.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Once- and twice-daily dosing with rosiglitazone improves glycemic control in patients with type 2 diabetes.

To determine the efficacy of rosiglitazone compared with placebo in reducing hyperglycemia. After a 4-week placebo run-in period, 959 patients were randomized to placebo or rosiglitazone (total daily dose 4 or 8 mg) for 26 weeks. The primary measure of efficacy was change in the HbA1c concentration. Rosiglitazone produced dosage-dependent reductions in HbA1c of 0.8, 0.9, 1.1, and 1.5% in the 4 mg o.d., 2 mg b.i.d., 8 mg o.d., and 4 mg b.i.d. groups, respectively, compared with placebo. Clinically significant decreases from baseline in HbA1c were observed in drug-naive patients at all rosiglitazone doses and in patients previously treated with oral monotherapy at rosiglitazone 8 mg o.d. and 4 mg b.i.d. Clinically significant decreases from baseline in HbA1c were also observed with rosiglitazone 4 mg b.i.d. in patients previously treated with combination oral therapy. Approximately 33% of drug-naive patients treated with rosiglitazone achieved HbA1c < or =7% at study end. The proportions of patients with at least one adverse event were comparable among the rosiglitazone and placebo groups. There was no evidence of hepatotoxicity in any treatment group. There were statistically significant increases in weight and serum lipids in all rosiglitazone treatment groups compared with placebo. For LDL and HDL cholesterol, the observed increase appeared to be dose related. Rosiglitazone at total daily doses of 4 and 8 mg significantly improved glycemic control in patients with type 2 diabetes and was well tolerated.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia.

Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone. We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals. Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005). Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

A one-year study comparing the efficacy and safety of rosiglitazone and glibenclamide in the treatment of type 2 diabetes.

This study was designed to compare the efficacy of rosiglitazone and glibenclamide in individuals with type 2 diabetes over a 12-month period. A total of 598 patients were randomized to double-blind treatment for 52 weeks with rosiglitazone 4 mg/d (n=200), rosiglitazone 8 mg/d (n=191) or glibenclamide (n=207; dose adjusted up to 15 mg/d over the first 12 weeks according to clinical response). Changes in fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), fasting insulin and its precursor peptides, and lipids were measured and safety was evaluated. Significant reductions in HbA1c levels at 52 weeks compared with baseline were seen in all treatment groups (rosiglitazone 4 mg/d=-0.3%, P=0.0003; rosiglitazone 8 mg/d=-0.5%, P<0.0001; glibenclamide=-0.7%, P<0.0001). Mean FPG levels were also significantly reduced in all treatment groups (rosiglitazone 4 mg/d=-1.4 mmol/l; rosiglitazone 8 mg/d=-2.3 mmol/l; glibenclamide=-1.7 mmol/l; P<0.0001 vs. baseline for all treatments). Rosiglitazone therapy reduced plasma insulin, proinsulin, split proinsulin and free fatty acid levels compared with glibenclamide. Rosiglitazone improved insulin resistance while a worsening was seen with glibenclamide. Total:high-density lipoprotein cholesterol ratios were reduced with glibenclamide and unchanged with rosiglitazone. All treatments were generally well tolerated. The efficacy of rosiglitazone 8 mg/d in improving glycaemic control in patients with type 2 diabetes is comparable to that of glibenclamide. However, rosiglitazone reduced insulin resistance and proinsulin levels whereas glibenclamide use was associated with an increase in fasting insulin and proinsulin. This suggests that in the long term, rosiglitazone may protect the beta-cell whereas glibenclamide is likely to increase the burden.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes.

This open-label, active-controlled study investigated the cardiac safety and antihyperglycemic effect of rosiglitazone (RSG) in patients with type 2 diabetes. Of the 203 patients randomly assigned to RSG (4 mg b.i.d.) or glyburide (GLB) (titrated to achieve optimal glycemic control for the first 8 weeks only to limit the risk of hypoglycemia; mean 10.5 mg/day), 118 had an echocardiogram performed at week 52. Left ventricular (LV) mass index, ejection fraction, and left ventricular end-diastolic volume were assessed by M-mode echocardiography at baseline and weeks 12, 28, and 52; 24-h ambulatory blood pressure was assessed at baseline and at weeks 28 and 52. Glycemic control was assessed by measuring fasting plasma glucose (FPG) and HbA(1c). Neither treatment produced an increase in LV mass index that exceeded 1 SD. Ejection fraction did not change in either group. Both groups had clinically insignificant increases in LV end-diastolic volume. RSG, but not GLB, caused a statistically significant reduction in ambulatory diastolic blood pressure. Both treatments reduced HbA(1c) and FPG. A total of 52 weeks of therapy with RSG (4 mg b.i.d.) did not adversely affect cardiac structure or function in patients with type 2 diabetes and produced significant and sustained reductions in hyperglycemia. Decreases in ambulatory diastolic blood pressure with RSG were superior to those with GLB.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy.

The efficacy of thiazolidinediones, as compared with other oral glucose-lowering medications, in maintaining long-term glycemic control in type 2 diabetes is not known. We evaluated rosiglitazone, metformin, and glyburide as initial treatment for recently diagnosed type 2 diabetes in a double-blind, randomized, controlled clinical trial involving 4360 patients. The patients were treated for a median of 4.0 years. The primary outcome was the time to monotherapy failure, which was defined as a confirmed level of fasting plasma glucose of more than 180 mg per deciliter (10.0 mmol per liter), for rosiglitazone, as compared with metformin or glyburide. Prespecified secondary outcomes were levels of fasting plasma glucose and glycated hemoglobin, insulin sensitivity, and beta-cell function. Kaplan-Meier analysis showed a cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide. This represents a risk reduction of 32% for rosiglitazone, as compared with metformin, and 63%, as compared with glyburide (P<0.001 for both comparisons). The difference in the durability of the treatment effect was greater between rosiglitazone and glyburide than between rosiglitazone and metformin. Glyburide was associated with a lower risk of cardiovascular events (including congestive heart failure) than was rosiglitazone (P<0.05), and the risk associated with metformin was similar to that with rosiglitazone. Rosiglitazone was associated with more weight gain and edema than either metformin or glyburide but with fewer gastrointestinal events than metformin and with less hypoglycemia than glyburide (P<0.001 for all comparisons). The potential risks and benefits, the profile of adverse events, and the costs of these three drugs should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00279045 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Effect of rosiglitazone versus insulin on the pancreatic beta-cell function of subjects with type 2 diabetes.

In a previous study, we found observational evidence of improvement in beta-cell function when rosiglitazone was added to a failing oral antihyperglycemic regimen consisting of sulfonylureas and metformin. To confirm our previous observations, we designed and performed a prospective, randomized, and controlled study. A total of 17 subjects with type 2 diabetes, inadequately controlled on a maximized oral antihyperglycemic double regimen of glimepiride and metformin, were randomized to the addition of rosiglitazone or insulin to their treatment regimens for a period of 6 months. At baseline and at 6 months, the following were performed: measurement of fasting plasma glucose, fasting proinsulin, and insulin levels; frequently sampled intravenous glucose tolerance test; and glucagon stimulation test for C-peptide. Nine subjects were randomized to the addition of 8 mg rosiglitazone, and eight subjects were randomized to the addition of one injection of insulin (premixed 70/30) before their evening meal. The treatment groups were well matched for age, duration of diabetes, and BMI. Most important, the HbA(1c) was well matched between groups before treatment (8.7 +/- 0.3 and 9.0 +/- 0.3%; NS) and at the end of the 6 months (7.8 +/- 0.5 and 7.8 +/- 0.3%; NS). After 6 months, at the end of the study, there was a significant improvement in acute insulin response to glucose in the rosiglitazone group (+15.3 microIU x ml(-1) x 10 min(-1); P < 0.001) that led to an increase in the disposition index from 0.18 at baseline to 4.18 at 6 months (P = 0.02). Furthermore, at the end of the study, the proinsulin-to-insulin ratio had decreased in the rosiglitazone group by 36% (P = 0.03) but did not change significantly in the insulin treatment group. Rosiglitazone, but not insulin, induced a recovery of pancreatic beta-cell function, as evidenced by the restoration of the first-phase insulin response to glucose, improvement in the disposition index, and a decrease in the proinsulin-to-insulin ratio in subjects with type 2 diabetes in whom oral antihyperglycemic therapy failed. This improvement was independent of the correction of glucotoxicity.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes.

Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone (P < 0.05) and metformin (P < 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% (P < 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% (P < 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1) improves insulin responsiveness in resting skeletal muscle and 2) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial.

Accumulating evidence suggests that combination therapy using oral antidiabetic agents with different mechanisms of action may be highly effective in achieving and maintaining target blood glucose levels. The aim of our study is to evaluate the differential effect on glucose and lipid parameters of the association between glimepiride plus metformin and rosiglitazone plus metformin in patients affected by type 2 diabetes and metabolic syndrome. Patients were enroled, evaluated and followed at two Italian centres. We evaluated 99 type 2 diabetic patients with metabolic syndrome (48 males and 47 females; 23 males and 24 females, aged 52 +/- 5 with glimepiride; 25 males and 23 females, aged 54 +/- 4 with cglitazone). All were required to have been diagnosed as being diabetic for at least 6 months and did not have glycaemic control with diet and oral hypoglycaemic agents such as sulphonylureas or metformin, both to the maximum tolerated dose. All patients took a fixed dose of metformin, 1500 mg/day. We administered glimepiride (2 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We evaluated body mass index (BMI), glycaemic control, lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglycerides] and lipoprotein parameters [apolipoprotein A-I and apolipoprotein B (Apo B)] during 12 months of this treatment. A total of 95 patients completed the study. Significant BMI decrease was observed at 12 months in glimepiride and rosiglitazone group (p < 0.05 and p < 0.01 respectively) as well as of glycated haemoglobin decrease (p < 0.05 and p < 0.01 respectively), mean fasting plasma glucose and postprandial plasma glucose levels (p < 0.05 and p < 0.01 respectively). A decrease in fasting plasma insulin and postprandial plasma insulin at 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group was observed. Furthermore, homeostasis model assessment index improvement was obtained only at 9 and 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group. Significant TC, LDL-C and Apo B improvement (p < 0.05 respectively) was present in glimepiride group after 12 months compared with the baseline values, and these variations were significant (p < 0.05) between groups. Of the 95 patients who completed the study, 8.5% of patients in glimepiride group and 12.5% of patients in rosiglitazone group had side-effects (p = not significant). Four patients had transient side-effects in glimepiride group and six patients in rosiglitazone group. Altogether, we did not have statistically significant changes in transaminases. The rosiglitazone-metformin association significantly improve the long-term control of all insulin-resistance-related parameters in comparison with the glimepiride-metformin-treated group. On the other side, glimepiride treatment is associated to a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with glimepiride: a twelve-month, multicenter, double-blind, randomized, controlled, parallel-group trial.

Glimepiride is approved as monotherapy and in combination with metformin or with insulin, whereas the combination of glimepiride with other antihyperglycemic drugs is under investigation. The aim of this study was to assess the differential effect on glucose and lipid variables and tolerability of the combination of glimepiride plus pioglitazone or rosiglitazone in patients with type 2 diabetes mellitus (DM) and metabolic syndrome. This 12-month, multicenter, double-blind, randomized, controlled, parallel-group trial was conducted at 3 study sites in Italy. We assessed patients with type 2 DM (duration, > or =6 months) and with metabolic syndrome. All patients were required to have poor glycemic control with, or to have experienced > or =1 adverse effect (AE) with, diet and oral hypoglycemic agents such as sulfonylureas or metformin, both given up to the maximum tolerated dose. All patients received a fixed oral dose of glimepiride, 4 mg/d divided into 2 doses, self-administered for 12 months. Patients also were randomized to receive oral pioglitazone (15 mg once daily) (G + P group) or oral rosiglitazone (4 mg once daily) (G + R group), self-administered for 12 months. We assessed body mass index (BMI), glycemic control (glycosylated hemoglobin [HbA(1c)], fasting and postprandial plasma glucose and insulin levels [FPG, PPG, FPI, and PPI, respectively], and homeostasis model assessment index), lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]), and lipoprotein variables (apolipoprotein [apo] A-I and apo B) at baseline and at 3, 6, 9, and 12 months of treatment. Treatment tolerability was assessed at each study visit using a thorough interview of patients, and comparisons of clinical and laboratory values to baseline levels. A total of 91 patients were enrolled in the study; 87 patients completed it (G + P group: 24 women, 21 men; mean [SD] age, 53 [6] years; G + R group: 20 women, 22 men; mean [SD] age, 54 [5] years). Patients in the G + P and G + R groups experienced significant increases in mean BMI at 12 months compared with baseline (4.92% and 6.17%, respectively; both, P < 0.05). The combination of glimepiride with pioglitazone or rosiglitazone significantly improved glycemic control in the study patients. At 12 months, we observed a 1.3% improvement in mean values for plasma HbA(1c) concentration (P < 0.01) 19.3% in FPG (P < 0.01), 16.3% in PPG (P < 0.01), 42.4% in FPI ), and 23.3% in PPI (P <0.05); no significant differences were found between treatment groups. Although the G + P group experienced a significant improvement at 12 months in almost all variables of lipid metabolism from baseline (TC, - 11%; LDL-C, -12%; HDL-C, 15%; and apo B, - 10.6% [all, P , 0.05]), the G + R group experienced a significant increase in mostly the lipid risk factors for cardiovascular disease (TC, 14.9%; LDL-C, 16.5%; TG, 17.9%; and apo B, 10.3% [all, P , 0.05]). Overall, no statistically significant changes in plasma aminotransferase activities were observed. Of the 87 patients who completed the study, 6.7% (3/45) of patients in the G + P group and 11.9% (5/42) of patients in the G + R group had transient, mild to moderate AEs that did not cause withdrawal from the trial. In this study of patients with type 2 DM and metabolic syndrome who did not respond adequately to, or experienced AEs with, diet and either a sulfonylurea or metformin previously, the combination of glimepiride plus pioglitazone was associated with a significant improvement in lipid and lipoprotein variables, whereas the combination of glimepiride plus rosiglitazone appears to not have had any clinically significant effect on lipid metabolism.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients.

Adiponectin, a plasma protein exclusively synthesized and secreted by adipose tissue, has recently been shown to have anti-inflammatory, antiatherogenic properties in vitro and beneficial metabolic effects in animals. Lower plasma levels of adiponectin have been documented in human subjects with metabolic syndrome and coronary artery disease. We investigated whether the level of this putative protective adipocytokine could be increased by treatment with a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist in diabetic patients. Type 2 diabetic patients (30 in the treatment group and 34 in the placebo group) were recruited for a randomized double-blind placebo-controlled trial for 6 months with the PPAR-gamma agonist rosiglitazone. Blood samples were collected and metabolic variables and adiponectin levels were determined in all patients before initiation of the study. In the rosiglitazone group, mean plasma adiponectin level was increased by more than twofold (P < 0.0005), whereas no change was observed in the placebo group. Multivariate linear regression analysis showed that whether rosiglitazone was used was the single variable significantly related to the changes of plasma adiponectin. The amount of variance in changes of plasma adiponectin level explained by the treatment was approximately 24% (r(2) = 0.24) after adjusting for age, sex, and changes in fasting plasma glucose, HbA(1c), insulin resistance index, and BMI. Rosiglitazone increases plasma adiponectin levels in type 2 diabetic subjects. Whether this may contribute to the antihyperglycemic and putative antiatherogenic benefits of PPAR-gamma agonists in type 2 diabetic patients warrants further investigation.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Combination therapy for type 2 diabetes: repaglinide plus rosiglitazone.

This 24-week, randomized, multicentre, open-label, parallel-group clinical trial compared efficacy and safety of repaglinide monotherapy, rosiglitazone monotherapy, and combination therapy (repaglinide plus rosiglitazone) in Type 2 diabetes after unsatisfactory response to sulphonylurea or metformin monotherapy. Enrolled patients (n = 252) were adults having Type 2 diabetes for at least 1 year, with HbA(1c) values > 7.0% after previous monotherapy (sulphonylurea or metformin, >/= 50% maximal dose). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, rosiglitazone, or repaglinide/rosiglitazone. Study treatments were initiated with a 12-week dose optimization period (doses optimized according to labelling), followed by a 12-week maintenance period. Efficacy endpoints were changes in HbA(1c) values (primary) or fasting plasma glucose values (secondary). Baseline HbA(1c) values were comparable (9.3% for repaglinide, 9.0% for rosiglitazone, 9.1% for combination). Mean changes in HbA(1c) values at the end of treatment were greater for repaglinide/rosiglitazone therapy (-1.43%) than for repaglinide (-0.17%) or rosiglitazone (-0.56%) monotherapy. Reductions of fasting plasma glucose values were also greater for combination therapy (-5.2 mmol/l, -94 mg/dl) than for repaglinide monotherapy (-3.0 mmol/l, -54 mg/dl) or rosiglitazone monotherapy (-3.7 mmol/l, -67 mg/dl). Minor hypoglycaemic events occurred in 9% of combination therapy patients, vs. 6% for repaglinide and 2% for rosiglitazone. Individual weight gains for combination therapy were correlated to HbA(1c) response. The combination therapy regimen was well tolerated. In patients previously showing unsatisfactory response to oral monotherapy, glycaemic reductions were greater for the repaglinide/rosiglitazone combination regimen than for use of either repaglinide or rosiglitazone alone.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes.

Metformin and rosiglitazone both improve glycemic control in type 2 diabetes mellitus, however may possess different anti-inflammatory and anti-atherosclerotic properties. We investigated the effects of these medications on high-sensitivity C-reactive protein (hsCRP) and carotid artery intima-media thickness (CIMT) to determine their relative potential to reduce cardiovascular risk independent of their antihyperglycemic actions. Ninety-two subjects with suboptimally controlled diabetes mellitus (hemoglobin A1c [HbA1c] >7.0%) were assigned to therapy with either rosiglitazone 4 mg once daily or metformin 850 mg twice daily for 24 weeks. The primary end point was the change in hsCRP after 24 weeks. The change in CIMT was prespecified as a secondary end point. Metformin and rosiglitazone treatment led to similar significant improvements in glycemic control (HbA1c -1.08% in the rosiglitazone group and -1.18% in the metformin group, P = nonsignificant). High-sensitivity C-reactive protein levels decreased by an average of 68% in the rosiglitazone group (5.99 +/- 0.88 to 1.91 +/- 0.28 mg/L, P < .001), compared with a nonsignificant 4% reduction in hsCRP with metformin (5.69 +/- 0.83 to 5.46 +/- 0.92 mg/L; P = nonsignificant). Maximal CIMT progressed in the metformin group (+0.084 +/- 0.038 mm), whereas regression of maximal CIMT was observed in the rosiglitazone group (-0.037 +/- 0.031 mm; P = .02 for the between group comparison). Similar changes were observed for mean CIMT. The change in hsCRP and maximal CIMT were related in a multivariable model controlling for changes in HbA1c and lipid parameters (r = .31; P = .01). Rosiglitazone, compared to metformin, induced a prompt and profound reduction in hsCRP levels independent of its effect on glycemia. This change was associated with regression of CIMT after 24 weeks.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Rosiglitazone versus bedtime insulin in the treatment of patients with conventional oral antidiabetic drug failure: a 1-year randomized clinical trial.

This study was conducted to evaluate the efficacy and tolerability of rosiglitazone in the treatment of patients with secondary oral antidiabetic drug (OAD) failure and to directly compare its use with bedtime insulin. A total of 112 Chinese patients with type 2 diabetes and conventional OAD failure were recruited. Patients were randomly assigned to treatment with rosiglitazone or bedtime isophane insulin; they continued to take their original oral antidiabetic drugs. Glycemic index, other clinical profiles, and tolerability were assessed during treatment and 1 y after add-on treatment was provided. Among the 112 patients, mean age (+/-SD) was 58.2+/-11.0 y (median, 58 y; range, 37 to 84 y). Both rosiglitazone (n=56) and insulin (n=56) significantly improved fasting glucose (2.4 and 3.7 mmol/L, respectively) and hemoglobin A1c concentrations (1.1% and 1.3%, respectively). Both therapies increased body mass index after 1 y of treatment (0.9 and 0.8 kg/m2, respectively). Only rosiglitazone increased high-density lipoprotein cholesterol concentrations (0.1 mmol/L). Four patients (7.1%) who were given rosiglitazone developed adverse effects (2, ankle edema, and 2, gastrointestinal disturbance). Six insulin-treated patients (10.7%) described adverse effects (5, early morning hypoglycemia, and 1, anxiety). Investigators concluded that in Chinese patients with type 2 diabetes and secondary conventional OAD failure, 1 y of treatment with rosiglitazone or bedtime insulin added to the regular regimen resulted in similar improvements in glycemic control. Rosiglitazone was also associated with improved high-density lipoprotein cholesterol levels. The addition of rosiglitazone may offer a safe and effective alternative to bedtime insulin treatment.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with metformin.

Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin, whereas the combination of metformin with thiazolidinediones is relatively less studied. The aim of the present study was to assess the differential effect on glycaemic metabolism and lipid variables of the combination of metformin plus pioglitazone or metformin plus rosiglitazone in diabetic patients with metabolic syndrome. All patients began metformin and were randomized to receive pioglitazone or rosiglitazone for 12 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin, homeostasis model assessment index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B. Significant decreases in glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, and postprandial plasma insulin were seen after 9 and 12 months in both groups. Homeostasis model assessment index improved at 12 months in both groups. Significant total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B improvement was observed in pioglitazone group after 12 months, but not in the rosiglitazone group. These variations were significant between groups. The combination of metformin plus thiazolidinediones was able to improve glycaemic control compared with previous therapy. Pioglitazone was associated with a significant improvement in lipid and lipoprotein variables.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy.

This double-blind study evaluated the efficacy and safety of metformin-glibenclamide tablets vs. metformin plus rosiglitazone therapy in patients with type 2 diabetes inadequately controlled on metformin monotherapy. After an open-label, metformin lead-in phase, 318 patients were randomly assigned to treatment based on metformin-glibenclamide 500/2.5 mg tablets (initial daily dose 1000/5 mg) or metformin 500 mg plus rosiglitazone 4 mg (initial daily dose 1000-2000 mg + 4 mg, depending on previous treatment) for 24 weeks. Doses were titrated to achieve the therapeutic glycaemic target. The primary efficacy variable was the change in HbA1C. At week 24, metformin-glibenclamide tablets resulted in significantly greater reductions in HbA1C (-1.5%) and fasting plasma glucose [-2.6 mmol/l (-46 mg/dl)] than metformin plus rosiglitazone [-1.1%, p < 0.001; -2 mmol/l (-36 mg/dl), p = 0.03]. More patients receiving metformin-glibenclamide attained HbA1C <7.0% than did those in the metformin plus rosiglitazone group (60 vs. 47%) and had fasting plasma glucose levels <7 mmol/l (<126 mg/dl) by week 24 (34 vs. 25%). Both treatments were well tolerated. Frequency of adverse gastrointestinal events was comparable between groups. Four per cent of patients receiving metformin-glibenclamide withdrew because of symptomatic hypoglycaemia contrasted with 3% of patients receiving metformin plus rosiglitazone who withdrew because of persistent hyperglycaemia. Hypoglycaemic events were mild or moderate in intensity and were easily self-managed. Metformin-glibenclamide tablets resulted in significantly greater reductions in HbA1C and fasting plasma glucose compared with metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy.

CD006063

New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

The effects of rosiglitazone and metformin on the plasma concentrations of resistin in patients with type 2 diabetes mellitus.

Resistin is a protein secreted from adipose tissue that is thought to play a role in insulin sensitivity. We examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus who showed poor glycemic control with glimepiride (4 mg/d) were randomized to rosiglitazone (4 mg/d) and metformin (500 mg bid) treatment groups. All subjects continued glimepiride treatment as well. The plasma concentrations of resistin were measured at baseline and at 6 months of treatment for both groups. The anthropometric parameters, fasting plasma glucose, HbA1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol, free fatty acids, and adiponectin concentrations were also measured. After 6 months of treatment, the reduction in plasma glucose levels was similar between the 2 groups. There were no significant changes in the lipid profiles of either group during the study period. The plasma resistin levels decreased in the rosiglitazone group (2.49 +/- 1.93 vs 1.95 +/- 1.59 ng/ml; P < .05) but increased in the metformin group (2.61 +/- 1.69 vs 5.13 +/- 2.81 ng/ml; P < .05). The plasma adiponectin concentrations were increased in the rosiglitazone group (2.91 +/- 1.46 vs 4.23 +/- 1.77 microg/ml; P < .05) but were unchanged in the metformin group. In summary, rosiglitazone treatment decreased the plasma resistin levels whereas metformin treatment increased them in patients with type 2 diabetes mellitus showing poor glycemic control with sulfonylurea therapy. These results suggest that the observed changes in plasma resistin levels are not the consequences of improved insulin resistance, nor are they consequences of glycemic control. Considering the potential role of resistin in insulin resistance, decrease in resistin levels may contribute to improving insulin action with rosiglitazone treatment.

CD001531

Pedestrian safety education can result in improvement in children's knowledge and can change observed road crossing behaviour, but whether this reduces the risk of pedestrian motor vehicle collision and injury occurrence is unknown. There is evidence that changes in safety knowledge and observed behaviour decline with time, suggesting that safety education must be repeated at regular intervals.

The effectiveness of parents in promoting the development of road crossing skills in young children.

Young children show poor judgment when asked to select a safe place to cross the road, frequently considering dangerous sites to be safe. Correspondingly, child pedestrian accidents are over-represented at such locations. Increasing the child's ability to recognise such dangers is a central challenge for road safety education. Practical training methods have proved effective in improving such judgments but are labour-intensive, time-consuming and therefore difficult to implement on a realistic scale. The study examined the possibility that volunteers from the local community might be capable of using such methods to promote children's pedestrian competence. Sixty children from the Primary 1 (Reception) classes of three Glasgow schools took part. Volunteers were ordinary parents from the same areas. None had 'formal' experience of working with children other than through being parents. Volunteers received experience of training children at courses organised in each school. Children learned in small groups, receiving two sessions of roadside training followed by four on a table-top model. Pre- and post-tests allowed the effectiveness of training to be assessed. Significant improvements relative to controls were found in all children following training. Improvements proved robust and no deterioration was observed two months after the programme ended. Comparison with a previous study in which training was undertaken by highly qualified staff showed that the volunteers were as effective as 'expert' trainers. Parent volunteers can significantly increase the pedestrian competence of children as young as five years. They constitute a most valuable 'resource' in road safety education. The opportunities afforded by involving the local community in educational interventions should be further explored.

CD001531

Pedestrian safety education can result in improvement in children's knowledge and can change observed road crossing behaviour, but whether this reduces the risk of pedestrian motor vehicle collision and injury occurrence is unknown. There is evidence that changes in safety knowledge and observed behaviour decline with time, suggesting that safety education must be repeated at regular intervals.

An evaluation of a safety education program for kindergarten and elementary school children.

To determine the effectiveness of a safety education program, Safety City, that is designed to teach kindergarten and first grade children how to cross the street, call 911 in an emergency, and avoid strangers. Kindergarten students at 10 urban elementary schools. Each school was randomized to either the intervention or control group. An evaluation tool was administered to all participants as a pretest. The Safety City program was then presented to the intervention schools. Afterward, the same evaluation tool was used as a post-test. The posttest was administered to the intervention group 6 months after the Safety City program was presented. The control group took the posttest 6 months after the pretest. Change in individual test scores. One hundred eighty-one children completed the pretest and posttest evaluations. There was no statistical difference in the change between pretest and posttest scores of children who participated in the Safety City program and those in the control group (crossing the street, P = .29; calling 911, P = .41; stranger avoidance, P = .57). Exposure to the Safety City program did not achieve the desired changes in safety knowledge among participants. This is most likely owing to the fact that Safety City attempts to convey a large amount of relatively complex information to young children in a brief period. We conclude that programs such as Safety City are not sufficient to teach children these behaviors. This report also emphasizes the importance of building an evaluation component into educational programs.

CD001531

Pedestrian safety education can result in improvement in children's knowledge and can change observed road crossing behaviour, but whether this reduces the risk of pedestrian motor vehicle collision and injury occurrence is unknown. There is evidence that changes in safety knowledge and observed behaviour decline with time, suggesting that safety education must be repeated at regular intervals.

A controlled group study of pedestrian-skill training for the mentally retarded.

CD009107

The outcomes reported severely limit conclusions for clinical practice. We found little robust evidence that sterile water is effective for low back or any other labour pain. Neither did we find any difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labour.

Intracutaneous Injections of Sterile Water over the Secrum for Labour Analgesia.

During first stage of labour, many women suffer from lower back pain. Since cutaneous afferents from the lower back converge to the dorsal horns in the same segments there is anatomical support for the lower back pain being a referred pain. Intracutaneous injections of sterile water in the skin over the sacrum have been shown to relieve the pain of labour and it is free from negative side effects associated with use of other methods. The study was conducted after approval of institutional ethical committee on 100 pregnant patients admitted to the labour room of Lok Nayak hospital, New Delhi. Patients received 4 intracutaneous injections of sterile water or normal saline 0.5ml in the lumbo-sacral region. Pain scores, progress of labour and fetal outcome were studied. There was significant reduction of pain scores in the sterile water group but not in the normal saline group at 10, 45 and 90 minutes after injection. There was no difference in the progress of labour and fetal outcome between the two groups. To conclude intracutoneous sterile water injections over the sacrum is a simple and effective method to control pain during labour.

CD009107

The outcomes reported severely limit conclusions for clinical practice. We found little robust evidence that sterile water is effective for low back or any other labour pain. Neither did we find any difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labour.

Labour pain treated with cutaneous injections of sterile water: a randomised controlled trial.

To evaluate the relief of pain in labour with subcutaneous and intracutaneous injections of sterile water, compared with placebo. Randomised controlled trial. Labour ward with approximately 3000 deliveries annually in a suburban area near Gothenburg, Sweden. Ninety-nine pregnant women at term, requiring pain relief for severe lower back pain during the first stage of labour. The women were randomised to receive four injections of 0.1 mL sterile water (without salt) intracutaneously (n = 33), four injections of 0.5 mL sterile water subcutaneously (n = 33) or placebo treatment (n = 33). Reduction of labour pain measured by visual analogue scale. The median visual analogue scale pain score for labour pain was significantly lower compared with initial values in the two study groups and compared with placebo at 10 and 45 minutes after treatment. The median reductions in visual analogue scores after 10 minutes were 5.0 cm and 4.5 cm in the intracutaneous and subcutaneous injection groups, respectively; women in the placebo group scored a median reduction of 1.7 cm. After 45 minutes the median reductions in the visual analogue scores were 4.9 cm and 4.0 cm in the intracutaneous and subcutaneous injection groups, respectively, compared with 1.0 cm for women in the placebo group. No significant differences in analgesic effect or pain experienced during administration were found between the two study groups. The new subcutaneous method of administering sterile water, as well as the earlier described intracutaneous injection method, were effective for the relief of pain in labour.

CD009107

The outcomes reported severely limit conclusions for clinical practice. We found little robust evidence that sterile water is effective for low back or any other labour pain. Neither did we find any difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labour.

Effectiveness of subcutaneous injection of sterile water to the lower back for pain relief in labor.

The analgesic efficacy of subcutaneous injection of sterile water compared to isotonic saline was investigated in a randomized, controlled study on a total of 100 women in the active phase of labor and who complained of low back pain. Pain perception was rated on a numerical rating scale before and at 10 and 45 minutes after the injection. The initial pain score was the same in both groups and pain relief was expressed by both groups irrespective of the solution injected, but the sterile water group had significantly higher relief scores compared to those receiving saline. This was not influenced by maternal age, parity, education, body mass index, cervical dilatation at intervention or fetal size, suggesting that subcutaneous injection of sterile water to the lower back provides relief from back pain during labor.

CD009107

The outcomes reported severely limit conclusions for clinical practice. We found little robust evidence that sterile water is effective for low back or any other labour pain. Neither did we find any difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labour.

Parturition pain treated by intracutaneous injections of sterile water.

Forty-five pregnant women in the first stage of labour presenting with lower back pain were randomized into 2 groups. One group received intracutaneous injections of sterile water in the lumbosacral region, while the other group was given corresponding subcutaneous injections of isotonic saline, regarded as a placebo treatment. In the group that received intracutaneous sterile water injections the mean VAS score was significantly more reduced compared to the placebo group at 10 min (P less than 0.001), 45 min (P less than 0.02), and at 90 min (P less than 0.05) after the treatment. The midwives' blind estimation of the effectiveness of treatment was consistent with the VAS assessment. However, the requirement of pethidine (meperidine) was similar in the 2 groups. The analgesic method presented was found to be an effective treatment against lower back pain during the first stage of labour and it is speculated that the mode of action resembles acupuncture.

CD009107

The outcomes reported severely limit conclusions for clinical practice. We found little robust evidence that sterile water is effective for low back or any other labour pain. Neither did we find any difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labour.

The effect of sterile water blocks on low back labor pain.

To evaluate the analgesic effect of intradermal sterile water blocks, 272 women in labor complaining of severe low back pain were randomly assigned to treatment with either sterile water or saline solution blocks. Pain intensity was assessed on a visual analog scale, before the blocks were given and again 1 and 2 hours later. The groups were equal with regard to age, parity, fetal size, progression of labor, and initial pain scoring. Pain scoring 1 and 2 hours after the blocks were given showed a significantly higher degree of analgesia in the sterile water group. No adverse effects were noted, and patient acceptability was high.

CD009107

The outcomes reported severely limit conclusions for clinical practice. We found little robust evidence that sterile water is effective for low back or any other labour pain. Neither did we find any difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labour.

Subcutaneous sterile water injection for labour pain: a randomised controlled trial.

About 30% of women experience severe continuous low-back pain in labour, but limited options are available to reduce this pain especially in developing countries and remote areas. To evaluate the efficacy of subcutaneous sterile water injection in reduction of labour pain compared with placebo. One hundred (100) consecutive patients were enrolled in a double-blind randomised controlled trial. During the first stage of labour with planned normal vaginal delivery, the intervention group (n = 50) received 0.5 mL sterile water injected subcutaneously and the control group (n = 50) received normal saline as a placebo. Pain score was measured before and 10 and 45 min after the injection, using the faces rating scale. Low-back labour pain. The two groups were not significantly different regarding maternal age and weight, gestational age, parity and gravidity and degree of effacement. The median pain score was equal in both groups prior to the injection. Pain severity was reduced in both groups after the injection. However, the median pain score in the sterile water group was significantly lower than the placebo group 10 min (P < 0.01), as well as 45 min, after the injection (P < 0.01). Administering one subcutaneous injection of sterile water in a painful point of the lumbosacral area is effective in reducing low-back pain during labour.

CD009107

The outcomes reported severely limit conclusions for clinical practice. We found little robust evidence that sterile water is effective for low back or any other labour pain. Neither did we find any difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labour.

Relief of low back labor pain by using intracutaneous injections of sterile water: a randomized clinical trial.

To study the effectiveness of intracutaneous injections of sterile water in relieving low back pain during labor in Thai women. Randomized controlled trial. Department of Obstetrics and Gynecology, Taksin Hospital, Bangkok. Fifty pregnant women at term, requiring pain relief for severe low back pain during the first stage of labor. The women were randomized to receive either 4 intracutaneous injections of 0.1 mL sterile water (n = 25) or isotonic saline as placebo (n = 25). Pain scores measured by visual analogue scale. Mean pain scores were significantly lower among the treatment group compared to the placebo group at 30 minutes, 1 and 2 hours after injections (p = 0.018, 0.046, and 0.027 respectively). Mean pain reduction were significantly greater in the treatment group compared to the placebo group at 30 minutes, 1 and 2 hours after injections (p < 0.001). There was no difference between the two groups with regard to time to delivery and rate of instrumental and cesarean delivery. The intracutaneous injections of sterile water was found to be an effective treatment against lower back pain during the first stage of labor.

CD003669

There is no reliable evidence from the trials reviewed concerning the effect of spinal as compared to general anaesthesia on the incidence of post-operative apnoea, bradycardia, or oxygen desaturation in ex-preterm infants undergoing herniorrhaphy. The estimates of effect in this review are based on a total population of only 108 patients or fewer. A large well designed randomised controlled trial is needed to determine if spinal anaesthesia reduces post-operative apnoea in ex-preterm infants not pretreated with sedatives. Adequate blinding, follow up and intention to treat analysis are required.

Post-operative recovery after inguinal herniotomy in ex-premature infants: comparison between sevoflurane and spinal anaesthesia.

We prospectively studied the post-operative recovery profile of 28 ex-premature infants undergoing inguinal herniotomy. All infants had a post-conceptual age of less than 46 weeks at the time of surgery and were randomized to receive either sevoflurane (group 1, 14 patients) or spinal anaesthesia (group 2, 14 patients). All patients received supplemental caudal analgesia before skin incision. Cardiorespiratory function was continuously recorded in all patients before and after surgery. A blinded observer analysed each paired recording for predefined episodes of apnoea, hypoxaemia or bradycardia and the reports were used to compare the two groups. Spinal anaesthesia was attempted unsuccessfully in four patients in group 2. Five patients in group 1 demonstrated an 'excess' number of episodes (median 4, range 3-12) of clinically silent post-operative cardiorespiratory complications. ('Excess' in our study was defined as a 3-fold or greater increase in the number of post-operative episodes of bradycardia or apnoea relative to pre-operative occurrence). Three of these patients had pre-existing abnormal respiratory function and accounted for 80% of the episodes (26/32) of post-operative bradycardia and all five episodes of post-operative apnoea identified. All episodes of bradycardia and apnoea were temporally unrelated. None of the remaining patients in group 2 demonstrated an unacceptable number of post-operative cardiorespiratory complications. Our limited study suggests that general anaesthesia with an inhalational agent such as sevoflurane may induce or unmask abnormalities of cardiopulmonary function in predisposed infants. Spinal anaesthesia may be preferable but it is potentially stressful for the infant and associated with a clinically significant failure rate.

CD003669

There is no reliable evidence from the trials reviewed concerning the effect of spinal as compared to general anaesthesia on the incidence of post-operative apnoea, bradycardia, or oxygen desaturation in ex-preterm infants undergoing herniorrhaphy. The estimates of effect in this review are based on a total population of only 108 patients or fewer. A large well designed randomised controlled trial is needed to determine if spinal anaesthesia reduces post-operative apnoea in ex-preterm infants not pretreated with sedatives. Adequate blinding, follow up and intention to treat analysis are required.

Postoperative apnea, bradycardia, and oxygen desaturation in formerly premature infants: prospective comparison of spinal and general anesthesia.

Eighteen formerly premature infants scheduled for inguinal herniorrhaphy and who were less than 51 wk postconceptional age were assigned to either the general anesthesia group (GA: atropine, halothane, and nitrous oxide) or the spinal anesthesia group (SA: hyperbaric tetracaine). Twelve-hour, three-channel continuous recordings of respiratory rate (chest wall impedance), electrocardiogram (ECG), and hemoglobin O2 saturation (SpO2) were obtained preoperatively and after surgery. These were analyzed for short (11-15s) and long (> 15 s) apnea spells, periodic breathing, and episodes of hemoglobin oxygen desaturation and bradycardia. Infants in the GA group had lower postoperative minimum SpO2 (68.7% +/- 11.4%) and minimum heart rate (79 bpm +/- 19) than infants in the SA group (80.7% +/- 9.2%, and 109 bpm +/- 30, respectively; P < 0.05) and had lower postoperative minimum SpO2 and minimum heart rate than they had preoperatively (79.0% +/- 13.7%, and 93 bpm +/- 31, respectively; P < 0.05); pre- and postoperative studies in the SA group did not differ. There were no differences in the incidence of postoperative central apnea. We conclude that spinal anesthesia reduces postoperative hemoglobin oxygen desaturation and bradycardia in formerly premature infants undergoing inguinal herniorrhaphy.

CD003669

There is no reliable evidence from the trials reviewed concerning the effect of spinal as compared to general anaesthesia on the incidence of post-operative apnoea, bradycardia, or oxygen desaturation in ex-preterm infants undergoing herniorrhaphy. The estimates of effect in this review are based on a total population of only 108 patients or fewer. A large well designed randomised controlled trial is needed to determine if spinal anaesthesia reduces post-operative apnoea in ex-preterm infants not pretreated with sedatives. Adequate blinding, follow up and intention to treat analysis are required.

Postoperative outcome in high-risk infants undergoing herniorrhaphy: comparison between spinal and general anaesthesia.

The incidence of inguinal hernia is higher in premature infants, particularly in low birth weight neonates. This latter group may also incur increased postoperative respiratory complications and inpatient admissions. The purpose of this study was to compare the effects of general and spinal anaesthesia on postoperative respiratory morbidity and on the length of hospital stay in high-risk infants undergoing inguinal herniorrhaphy. Forty patients, all high-risk infants who underwent unilateral or bilateral herniorrhaphies, were randomly assigned to receive general anaesthesia (n = 20) or spinal anaesthesia (n = 20). There was a significant difference in respiratory morbidity between the two groups, as well as a significant difference in the inpatient hospital stay. The present study suggests that spinal anaesthesia can be used safely for high-risk infants, preterm or formerly preterm, undergoing inguinal hernia repair.

CD003669

There is no reliable evidence from the trials reviewed concerning the effect of spinal as compared to general anaesthesia on the incidence of post-operative apnoea, bradycardia, or oxygen desaturation in ex-preterm infants undergoing herniorrhaphy. The estimates of effect in this review are based on a total population of only 108 patients or fewer. A large well designed randomised controlled trial is needed to determine if spinal anaesthesia reduces post-operative apnoea in ex-preterm infants not pretreated with sedatives. Adequate blinding, follow up and intention to treat analysis are required.

Postoperative apnea in former preterm infants: prospective comparison of spinal and general anesthesia.

Thirty-six former preterm infants undergoing inguinal hernia repair were studied. All were less than or equal to 51 weeks postconceptual age at the time of operation. Patients were randomly assigned to receive general or spinal anesthesia. Group 1 patients received general inhalational anesthesia with neuromuscular blockade. Group 2 patients received spinal anesthesia using 1% tetracaine 0.4-0.6 mg/kg in conjunction with an equal volume of 10% dextrose and 0.02 ml epinephrine 1:1000. In the first part of the study, infants randomized to receive spinal anesthesia also received sedation with im ketamine 1-2 mg/kg prior to placement of the spinal anesthetic (group 2 A). The remainder of group 2 patients did not receive sedation (group 2 B). Respiratory pattern and heart rate were monitored using an impedance pneumograph for at least 12 h postoperatively. Tracings were analyzed for evidence of apnea, periodic breathing and/or bradycardia by a pulmonologist unaware of the anesthetic technique utilized. None of the patients who received spinal anesthesia without ketamine sedation developed postoperative bradycardia, prolonged apnea, or periodic breathing. Eight of nine infants (89%) who received spinal anesthesia and adjunct intraoperative sedation with ketamine developed prolonged apnea with bradycardia. Two of the eight infants had no prior history of apnea. Five of the 16 patients (31%) who received general anesthesia developed prolonged apnea with bradycardia. Two of these five infants had no prior history of apnea. When infants with no prior history of apnea were analyzed separately, there was no statistically significant increased incidence of apnea in children receiving general versus spinal anesthesia with or without ketamine sedation. Because of the small numbers of patients studied, and the multiple factors that may influence the incidence of postoperative apnea (e.g., prior history of neonatal apnea), standard postoperative respiratory monitoring of these high-risk infants is still recommended following all anesthetic techniques.

CD003150

Aroma therapy showed benefit for people with dementia in the only trial that contributed data to this review, but it is important to note there were several methodological difficulties with this study. More well designed large-scale RCTs are needed before clear conclusions can be drawn on the effectiveness of aroma therapy. Additionally, several issues need to be addressed, such as whether different aroma therapy interventions are comparable and the possibility that outcomes may vary for different types of dementia.

Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa.

Behavioral and psychological symptoms in dementia are frequent and are a major management problem, especially for patients with severe cognitive impairment. Preliminary reports have indicated positive effects of aromatherapy using select essential oils, but there are no adequately powered placebo-controlled trials. We conducted a placebo-controlled trial to determine the value of aromatherapy with essential oil of Melissa officinalis (lemon balm) for agitation in people with severe dementia. Seventy-two people residing in National Health Service (U.K.) care facilities who had clinically significant agitation in the context of severe dementia were randomly assigned to aromatherapy with Melissa essential oil (N = 36) or placebo (sunflower oil) (N = 36). The active treatment or placebo oil was combined with a base lotion and applied to patients' faces and arms twice a day by caregiving staff. Changes in clinically significant agitation (Cohen-Mansfield Agitation Inventory [CMAI]) and quality of life indices (percentage of time spent socially withdrawn and percentage of time engaged in constructive activities, measured with Dementia Care Mapping) were compared between the 2 groups over a 4-week period of treatment. Seventy-one patients completed the trial. No significant side effects were observed. Sixty percent (21/35) of the active treatment group and 14% (5/36) of the placebo-treated group experienced a 30% reduction of CMAI score, with an overall improvement in agitation (mean reduction in CMAI score) of 35% in patients receiving Melissa balm essential oil and 11% in those treated with placebo (Mann-Whitney U test; Z = 4.1, p < .0001). Quality of life indices also improved significantly more in people receiving essential balm oil (Mann-Whitney U test; percentage of time spent socially withdrawn: Z = 2.6, p = .005; percentage of time engaged in constructive activities: Z = 3.5, p = .001). The finding that aromatherapy with essential balm oil is a safe and effective treatment for clinically significant agitation in people with severe dementia, with additional benefits for key quality of life parameters, indicates the need for further controlled trials.

CD003150

Aroma therapy showed benefit for people with dementia in the only trial that contributed data to this review, but it is important to note there were several methodological difficulties with this study. More well designed large-scale RCTs are needed before clear conclusions can be drawn on the effectiveness of aroma therapy. Additionally, several issues need to be addressed, such as whether different aroma therapy interventions are comparable and the possibility that outcomes may vary for different types of dementia.

Aromatherapy and behaviour disturbances in dementia: a randomized controlled trial.

A random controlled trial of the relaxing effects of an aromatherapy massage on disordered behaviour in dementia was conducted. Twenty-one patients were randomly allocated into one of three conditions, aromatherapy and massage (AM), conversation and aromatherapy (CA) and massage only (M). AM showed the greatest reduction in the frequency of excessive motor behaviour of all three conditions. This reached statistical significance between the hours of three and four pm (p < 0.05). Post hoc analysis suggested that at this time of day the AM consistently reduced motor behaviour when compared with CA (p = 0.05). This provides preliminary evidence of a measurable sedative effect of aromatherapy massage on dementia within a robust scientific paradigm. Further research is recommended with an expanded sample size. Copyright 2001 John Wiley & Sons, Ltd.

CD003150

Aroma therapy showed benefit for people with dementia in the only trial that contributed data to this review, but it is important to note there were several methodological difficulties with this study. More well designed large-scale RCTs are needed before clear conclusions can be drawn on the effectiveness of aroma therapy. Additionally, several issues need to be addressed, such as whether different aroma therapy interventions are comparable and the possibility that outcomes may vary for different types of dementia.

Efficacy of aromatherapy (Lavandula angustifolia) as an intervention for agitated behaviours in Chinese older persons with dementia: a cross-over randomized trial.

Agitated behaviours among persons with dementia are distressing to both patients and their caregivers. As pharmacological interventions may be limited by their potentially adverse effects, the use of complementary therapies for treatment of agitation has become more popular and aromatherapy is the fastest growing one. This study investigates the effectiveness of lavandula angustifolia (lavender) in treating agitated behaviours of demented people in Hong Kong. It was a cross-over randomized trial. Seventy Chinese older adults with dementia were recruited; half were randomly assigned to the active group (lavender inhalation) for three weeks and then switched to control group (sunflower inhalation) for another three weeks; the other half did the opposite. Clinical response was evaluated using the Chinese versions of Cohen-Mansfield Agitation Inventory (CCMAI) and Neuropsychiatric Inventory (CNPI). The mean CCMAI total scores decreased from 24.68 to 17.77(t=10.79, df=69, p<0.001). The CNPI scores changed from 63.17 (SD=17.81) to 58.77 (SD=16.74) (t=14.59, df=69, p<0.001) after receiving Treatment A (Lavandula Angustifolia). There were no period and sequential effects noted. In summary, lavender is effective as an adjunctive therapy in alleviating agitated behaviours in Chinese patients with dementia. In a patient population particularly vulnerable to side effects of psychotropic medications, aromatherapy using lavender may offer an alternative option. Copyright (c) 2007 John Wiley & Sons, Ltd.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Adoption, reach and effectiveness of computer-based, practitioner delivered and combined smoking interventions in general medical practices: a three-arm cluster randomized trial.

Brief advice for smoking patients has not been sufficiently integrated in routine care. Computer-based interventions emerged as a time saving option that might help to exhaust the potential population impact of the general practice setting. 151 practices were randomly assigned to one of three intervention programs consisting in the delivery of: (1) brief advice by the practitioner; (2) individually tailored computer-generated letters; or (3) a combination of both interventions. We assessed three dimensions of population impact: (1) adoption, i.e., the rate of practices participating in the program; (2) reach, measured as the number of interventions provided within 7 months; (3) effectiveness, measured as smoking abstinence at 12-months follow-up. Among the practices, 70% adopted the program with no significant differences across study groups. Treatment was provided to 3086 adult smokers. Negative binomial regression analysis revealed that the number of interventions provided was higher in practices allocated to the tailored letter and combination intervention groups by 215% (p<.01) and 127% (p=.02), respectively, compared to the brief advice intervention group. Among the patients who received the combination of both intervention, the odds of point abstinence from smoking was increased by 65% (p=.02) and 32% (p=.01) compared to the brief advice and tailored letters intervention respectively. Comparing the number of abstinent patients at follow-up revealed that the tailored letter and combination interventions were superior to the brief advice intervention. Computer-based interventions alone or in addition to conventional practitioner-delivered advice can foster the participation of general medical practices in tobacco control. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Counselling against cigarette smoking. A controlled study from a general practice.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

[Efficacy of smoking cessation instruction for general smokers at an annual physical examination].

A randomized controlled trial was conducted to evaluate the efficacy of smoking cessation instruction given to general smokers at an annual physical examination. Four hundred and twenty-six male and 42 female clients were randomly assigned to an intervention group (I), and 413 males and 76 females were assigned to a control (C) group. The I group was given an approximately 2-minute smoking cessation instruction by physicians, answered a quiz concerning tobacco, chose their own behavioral goals and were handed a leaflet on how to quit smoking. Subjects in both groups responded to a self-administered questionnaire and a 6-month and 12-month follow-up was performed by post card or telephone. The I group received an encouragement card one month after instruction and abstainers of the I group were awarded a telephone card at the 6-month follow-up. The results were as follows: 1) The male I group exhibited 7.3% (6 months), 10.1% (12 months) abstinence rates and the male C group 4.4% (6 months), 5.3% (12 months), respectively. The difference in 12-month abstinence rates was statistically significant. 2) The female I group exhibited abstinence rates of 16.7% (6 months), 23.8% (12 months) and the female C group 14.5% (6 months), 17.1% (12 months), respectively. 3) A multivariate analysis of smoking cessation showed that lower nicotine dependency, strong determination for smoking cessation, and being female were significant factors for abstinence at the 6-month follow-up. At 12 months, the smoking cessation instruction also became a significant factor. These data suggest that a simple smoking cessation instruction at an annual physical examination was effective for general smokers.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

The effectiveness of two smoking cessation programmes for use in general practice: a randomised clinical trial.

To evaluate a structured, behavioural change, smoking cessation intervention designed for use within general practice. Randomised controlled clinical trial. General practices in Newcastle, Australia. 311 Patients identified as smokers by a screening question were enrolled in the study. Of these, 101 were assigned to a structured behavioural change programme, 104 to a simple advice programme adapted from previous research, and 106 to a control group. No significant differences were found between groups for demographic and smoking related variables before the study. Patients in the simple advice group received a brief statement of advice from the general practitioner as well as three pamphlets; those in the structured intervention group were given strategies which included attitude and behavioural change programmes as well as techniques to aid compliance. The amount of smoking in all groups was assessed by self reports with validation by measurement of salivary cotinine concentrations. Significant increase in cessation rates. Significant differences between controls and the structured behavioural change group were found at the one month follow up, but only for self reported abstinence. The simple advice programme did not produce any significant differences over the control group. General practitioner evaluation of the structured programme highlighted difficulties in relation to the duration of the intervention. Overall the structured programme in its present form did not appear to be an effective programme for use within general practice.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Effects of physician counseling on the smoking behavior of asbestos-exposed workers.

Physician antismoking advice has been shown to increase smoking cessation, particularly among patients who have medical problems or perceive themselves to be at risk. The present study tested three hypotheses: (a) providing 3 to 5 min of behavioral counseling regarding a cessation strategy would be more effective than simply warning the smoker to quit smoking; (b) smokers with abnormal pulmonary function would be more likely to comply with medical advice than would smokers with normal pulmonary function; and (c) that smokers with abnormal pulmonary function who receive behavioral counseling would be the group most likely to achieve prolonged abstinence. Asbestos-exposed smoking men undergoing screening in a mandated program for naval shipyard workers were categorized as having normal or abnormal pulmonary status on the basis of chest X ray and pulmonary function tests (PFT). They were then randomly assigned within PFT categories to receive either a simple warning or 3 to 5 min of behavioral cessation counseling from the physician who gave them the results of their pulmonary tests. Subjects' smoking status was evaluated at 3- and 11-month intervals following the physician intervention. Smokers who received behavioral counseling were more likely to quit and remain abstinent over the 11-month period (8.4% abstinent) than were smokers given a minimal warning (3.6% abstinent). Prolonged abstinence rates among abnormal PFT subjects (3.7%) did not differ from those of normals (5.9%). The group with normal PFT who received behavioral counseling achieved the highest level of abstinence (9.5%). Maintaining adequate physician compliance with the counseling protocol proved difficult; implications of this for future efforts are discussed.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Anti-smoking advice for young diabetic smokers: is it a waste of breath?

The effect of health counselling on the smoking habits of 60 diabetic patients (aged less than 40 years) was assessed. Measurement of breath carbon monoxide (CO) and urinary cotinine, a metabolite of nicotine, were used as objective markers of smoking. All patients wished to cease smoking and the impact of health counselling was reviewed in a 'Stop Smoking' clinic. In addition to routine advice on the health hazards of smoking, half the patients and their families also received further counselling during a home visit by a health visitor. After 6 months many of the 60 patients claimed to have reduced their cigarette consumption. However, the urinary cotinine concentrations did not confirm this. Only one patient actually stopped smoking and he had sustained a myocardial infarction during the study. There was a small but significant reduction of breath CO in the patients seen at home by the health visitor but the urinary cotinine concentrations were unchanged. This suggests that these patients abstained from smoking for only a few hours before attending the 'Stop Smoking' clinic.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Nicotine chewing gum in general practice: effect of follow up appointments.

Two hundred smokers who were judged by their general practitioner to be motivated to stop smoking were allocated to one of two groups. All were offered an initial appointment at which they were advised to stop smoking and offered nicotine gum. One group then received no further appointments. The other was offered four further appointments over three months. Both groups were followed up at six and 12 months. At one year follow up 15.5% overall had stopped smoking, 14% in the low and 17% in the high contact group. This is better than most results so far reported for nicotine chewing gum in general practice, suggesting that general practitioners can use it to good effect. We compare this result with others achieved in general practice.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Smoking cessation at the workplace. Results of a randomised controlled intervention study. Worksite physicians from the AIREL group.

To compare the effects of a worksite intervention by the occupational physician offering simple advice of smoking cessation with a more active strategy of advice including a "quit date" and extra support. Employees of an electrical and gas company seen at the annual visit by their occupational physicians. CRITERIA END POINTS: Smoking point prevalence defined as the percentage of smokers who were non-smokers at one year. Secondary criteria were the percentage of smokers who stopped smoking for more than six months and the difference in prevalence of smoking in both groups. Randomised controlled trial. The unit of randomisation was the work site physician and a random sample of the employees of whom he or she was in charge. The length of the follow up was one year. Each of 30 work site physicians included in the study 100 to 150 employees. Among 504 subjects classified as smokers at baseline receiving simple advice (group A) and 591 the more active programme (group B), 68 (13.5%) in group A and 109 (18. 4%) were non-smokers one year later (p=0.03; p=0.01 taking the occupational physician as the statistical unit and using a non-parametric test). Twenty three subjects (4.6%) in group A and 36 (6.1%) in group B (p=0.26) declared abstinence of six months or more. Among non-smokers at baseline, 3.4% in both groups were smokers after one year follow up. The prevalence of smokers did not differ significantly at baseline (32.9% and 32.4%, p=0.75). After the intervention the prevalence of smoking was 30.8% in group A and 28. 7% in group B (p=0.19). An increase of the mean symptoms score for depression in those who quit was observed during this period. A simple cessation intervention strategy during a mandatory annual examination, targeting a population of smokers independently of their motivation to stop smoking or their health status, showed a 36% relative increase of the proportion of smokers who quit smoking as compared with what can be achieved through simple advice.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

A randomised controlled trial of the effect on middle-aged men of advice to stop smoking.

A randomised controlled trial of smoking cessation is reported in 1445 male smokers aged 40-59 at high risk of cardiorespiratory disease. The 714 men in the intervention group were recalled for a series of personal interviews with a doctor. After one year, 51% of the intervention group reported that they were not smoking any cigarettes, and most of the others reported a reduction. Compared with the "normal care" group, the men in the intervention group showed a decline in the prevalence of sputum production and dyspnoea; ventilatory function did not improve but its rate of decline was significantly slowed. There were no evident effects on blood pressure levels, nor on electrocardiographic findings over three years, nor on sickness absence over one year. Mortality follow-up has continued for an average of 7.9 years; 98 (13.7%) of the intervention group have died, compared with 94 (12.9%) of the "normal care" group. The 95% confidence limits on mortality range from 2.63% in favour of intervention to 4.37% in favour of normal care. The power of the trial has been reduced by smoking cessation in the "normal care" group. It is concluded that smoking cessation in these middle-aged men improved the symptoms and progress of chronic bronchitis; but the reversibility of the risk of cigarettes to the smoker's life may have been overestimated in observational studies.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

"Sick of Smoking": evaluation of a targeted minimal smoking cessation intervention in general practice.

Several smoking intervention studies have been conducted overseas which use a minimal amount of general practitioners' time and are conducted within the constraints of a normal consultation. However, there are no published reports of minimal interventions in Australian general practice. This study reports on 1238 South Australian smokers who were assigned to a non-intervention control group or a group which received firm general practitioner advice to quit smoking plus literature. At one-year follow-up, 7.5% of smokers in the minimal advice group who had quit for six or more months remained non-smokers compared with 3.2% in the control group. If similar analytical procedures had been used in this study as were used in the benchmark study in England in 1979, the quit rate for this study would have been 11.3% in the intervention group, and 4.8% in the control group--a net gain of 6.5%. These results are discussed with regard to widespread implementation in Australian general practice.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Smoking cessation in family practice: the effects of advice and nicotine chewing gum prescription.

The efficacy of physician anti-smoking intervention with 289 patients in a family practice setting was assessed. The design included two treatment conditions, physician advice and physician advice plus the offer of nicotine chewing gum (NCG) prescription. A no-advice group permitted assessment of the effects of repeated testing. The NCG group had higher rates of abstinence at all follow-up points, but the difference approached statistical significance at 3 months only (p less than .10). Comparison of those who actually used NCG to all other groups revealed significantly more users were abstinent at 1- and 3-month follow-up. A similar pattern occurred for proportion attempting cessation and smoking reduction. A dose-response relationship of gum use to outcome was identified. Long-term users (greater than 20 days) had 86% abstinence at 3 months versus 18% for short-term users. Thus, NCG does appear to have a role in family practice for promoting short-term cessation.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Evaluation of a minimal-contact smoking cessation intervention in an outpatient setting.

We examined the ability of a provider-initiated, minimal-contact intervention to modify the smoking behavior of ambulatory clinic patients. Smokers at two outpatient sites were assigned to one of three groups: provider intervention only (PI); provider intervention plus self-help manual (PI/M); and usual care (control) group (C). The physician message emphasized the patient's personal susceptibility, the physician's concern, and the patient's ability to quit (self-efficacy). The nurse consultation concentrated on benefits and barriers associated with stopping, and on strategies for cessation. Telephone interviews were conducted with the 250 participants within a few days of their clinic visit and again at one and six months. Both PI and PI/M proved to be superior to usual care in motivating attempts to quit at both one-month and six-month follow-ups, and logistic regression analyses indicated that participants receiving the self-help manual in addition to the health provider message were between two and three times more likely to quit smoking during the study period than were participants in either of the other study groups.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Proactive interventions for smoking cessation in general medical practice: a quasi-randomized controlled trial to examine the efficacy of computer-tailored letters and physician-delivered brief advice.

To test the efficacy of (i) computer-generated tailored letters and (ii) practitioner-delivered brief advice for smoking cessation against an assessment-only condition; and to compare both interventions directly. Quasi-randomized controlled trial. A total of 34 randomly selected general practices from a German region (participation rate 87%). A total of 1499 consecutive patients aged 18-70 years with daily cigarette smoking (participation rate 80%). The tailored letters intervention group received up to three individualized personal letters. Brief advice was delivered during routine consultation by the practitioner after an onsite training session. Both interventions were based on the Transtheoretical Model of behaviour change. Self-reported point prevalence and prolonged abstinence at 6-, 12-, 18- and 24-month follow-ups. Among participants completing the last follow-up, 6-month prolonged abstinence was 18.3% in the tailored letters intervention group, 14.8% in the brief advice intervention group and 10.5% in the assessment-only control group. Assuming those lost to follow-up to be smokers, the rates were 10.2%, 9.7% and 6.7%, respectively. Analyses including all follow-ups confirmed statistically significant effects of both interventions compared to assessment only. Using complete case analysis, the tailored letters intervention was significantly more effective than brief advice for 24-hour [odds ratio (OR) = 1.4; P = 0.047] but not for 7-day point prevalence abstinence (OR = 1.4; P = 0.068) for prolonged abstinence, or for alternative assumptions about participants lost to follow-up. The study demonstrated long-term efficacy of low-cost interventions for smoking cessation in general practice. The interventions are suitable to reach entire populations of general practices and smoking patients. Computer-generated letters are a promising option to overcome barriers to provide smoking cessation counselling routinely.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Smoking cessation in patients: two further studies by the British Thoracic Society. Research Committee of the British Thoracic Society.

The effects of various smoking cessation strategies were studied in two multicentre trials with new patients attending hospital or a chest clinic because of a smoking related disease. In the first trial (study A, 1462 patients) the effect of the physician's usual advice to stop smoking was compared with the effect of the same advice reinforced by a signed agreement to stop smoking by a target date within the next week, two visits by a health visitor in the first six weeks, and a series of letters of encouragement from the physician. The second trial (study B, 1392 patients) compared (1) advice only, (2) advice supplemented by a signed agreement, (3) advice supplemented by a series of letters of encouragement, and (4) advice supplemented by a signed agreement and a series of letters of encouragement. Patients were reviewed at six months and those claiming to have stopped smoking were seen again at 12 months. Claims of abstinence were checked by carboxyhaemoglobin measurement. In study A 9% of the intervention group had succeeded in stopping smoking at six months compared with 7% of the "advice only" patients (p = 0.17). In study B success rates were 5.2%, 4.9%, 8.5%, and 8.8% respectively. The signed agreement did not influence outcome, whereas postal encouragement increased the effect of the physician's advice. In both studies patients reviewed clinically between the initial and the six month visit were more likely to stop smoking than those not reviewed. Success rates increased with age and men tended to do better than women. The studies suggest that physician's advice alone will persuade 5% of outpatients with a smoking related disease to stop smoking. Subsequent postal encouragement will increase the cessation rate by more than half as much again. Such small improvements in success rates are worth while, especially if they can be achieved cheaply and on a wide scale.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Brief physician-initiated quit-smoking strategies for clinical oncology settings: a trial coordinated by the Eastern Cooperative Oncology Group.

Although tobacco use by cancer patients increases the risk of relapse, diminishes treatment efficacy, and worsens quality of life, about one third of patients who smoked before their diagnosis continue to smoke. Because patients have regular contact with oncologists, the efficacy of a physician-based smoking cessation treatment was evaluated. Cancer patients (n = 432) were randomly assigned to either usual care or a National Institutes of Health (NIH) physician-based smoking intervention. The primary outcome was 7-day point prevalence abstinence at 6 and 12 months after study entry. At the 6-month follow-up, there was no significant difference in quit rates between the usual care (11.9%) and intervention (14.4%) groups, and there was no significant difference between the usual care (13.6%) and intervention (13.3%) groups at the 12-month follow-up. Patients were more likely to have quit smoking at 6 months if they had head and neck or lung cancer, began smoking after the age of 16, reported at baseline using a cessation self-help guide or treatment in the last 6 months, and showed greater baseline desire to quit. Patients were more likely to have quit smoking at 12 months if they smoked 15 or fewer cigarettes per day, had head and neck or lung cancer, tried a group cessation program, and showed greater baseline desire to quit. Finally, there was greater adherence among physicians to the NIH model for physician smoking treatment for patients in the intervention versus the usual care group. While training physicians to provide smoking cessation treatment to cancer patients can enhance physician adherence to clinical practice guidelines, physician smoking cessation interventions fail to yield significant gains in long-term quit rates among cancer patients.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Three year evaluation of a programme by general practitioners to help patients to stop smoking.

A controlled study was undertaken to measure the effectiveness of general practitioners' use of an intensive programme to help patients to stop smoking. Two hundred cigarette smokers who attended a general practice were allocated to either a treatment (n = 100) or a non-intervention control (n = 100) group. After the initial visit treatment consisted of an educational consultation and four follow up visits. Smoking state was assessed biochemically at six months and three years. Thirty five patients in the treatment group were abstinent at three years compared with eight in the control group (p less than 0.001). Sixty four patients attended the educational consultation and first follow up visit; of these, 45 were not smoking at the first follow up visit, 30 maintained abstinence up to six months, and 22 were still not smoking after three years. Among the 37 patients who completed the treatment programme and attended all the follow up visits 57% were abstinent at three years. The results of this study suggest that general practitioners can help patients to stop smoking.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

A randomized trial of smoking cessation interventions in general practice in Italy.

The purpose of this study was to examine the effectiveness of different practice-based approaches to assist patients of primary care physicians to quit smoking and sustain cessation. Forty-four nonsmoking general practitioners volunteered for the study. After a period of training, they randomized 923 smoking clients, unselected for motivation toward quitting, to four different intervention groups: (i) minimal intervention, consisting of one single counselling session and a brief handout on quitting techniques; (ii) repeated counselling including reinforcing sessions at Months 1, 3, 6, and 9; (iii) repeated counselling and use of nicotine gum; and (iv) repeated counselling and spirometry. Biochemically validated smoking status was assessed at six and 12 months after recruitment. The proportion of verified quitters at 12 months was 4.8 percent among subjects randomized to the minimal intervention group, compared to 5.5 percent, 7.5 percent, and 6.5 percent among those randomized to the three repeated-counselling groups. In no treatment group was the outcome significantly different from that for one-time counselling at the (P less than 0.05) level. Lack of power, contamination, and low attendance at reinforcing sessions should be taken into account in interpreting the results.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Reaching midlife and older smokers: tailored interventions for routine medical care.

Although older adults can achieve significant health benefits from smoking cessation, few programs have specifically targeted this population. This study tested the effectiveness of an office-based smoking cessation program tailored to midlife and older smokers. This paper describes a randomized controlled trial comparing usual care with physician-delivered brief quit-smoking advice and counseling for midlife and older smokers (ages 50-74). Outpatient medical practices assigned to the Immediate Intervention (experimental) condition were trained to deliver brief quit-smoking advice and counseling. Delayed Intervention (control) practices followed usual care procedures. Thirty-nine practices accruing five or more patients per practice were included in the analyses. Using conservative measure of quitting, self-reported quit rates at 6-month follow-up were 15.41% for the Immediate Intervention group versus 8.16% of subjects in the Delayed Intervention group (P < 0.005). Baseline subject (N = 659) characteristics related to 6-month abstinence included number of previous quit attempts, quitting for 24 hr in the past year, desire to quit, confidence in quitting, perceived health benefits, and lower nicotine dependence. Smoking abstinence was significantly increased by training physicians and key office and clinical staff to intervene with older smokers. Brief interventions are tailored to this age cohort can be successfully and efficaciously integrated into routine care.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Is smoking intervention in general practice more successful among pregnant than non-pregnant women?

The objective of this study was to evaluate the effect of a simple smoking intervention programme, carried out by a large number of general practitioners (GPs) among pregnant and non-pregnant women. Four groups of women were defined by the dichotomies pregnant versus non-pregnant and intervention versus control. The intervention was semistructured, using a flip-over and a booklet, and it was implemented in an ordinary sequence of consultations. The study involved 187 GPs in western Norway. The subjects were 350 daily smoking pregnant women and 274 daily smoking non-pregnant women, 18-34 years of age. The point prevalence abstinence rate at 18 months was 15 and 20% for pregnant and non-pregnant women, respectively, in the intervention groups, and 7% in the control groups (Ppregnant = 0.06, Pnon-pregnant = 0.006). Twenty-five per cent of the pregnant women and 34% of the non-pregnant women reported that they had reduced their cigarette consumption, but had not stopped smoking entirely. If we include all drop-outs as smokers, the continuous abstinence rate during 15 months was 6%/0% among pregnant women (intervention/control) and 5%/1% among non-pregnant women. Stopping smoking was associated with having a non-smoking partner (P = 0.001), and being encouraged to do so by their partner (P = 0.004). The prevalence of both pregnant and non-pregnant women who stopped smoking was higher in the intervention than in the control groups. Pregnant women stopped smoking as frequently as non-pregnant individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Effects of nicotine chewing gum and follow-up appointments in physician-based smoking cessation.

The effect of different follow-up programs reinforced or not reinforced with the nicotine chewing gum Nicorette was tested by 13 physicians working in the open health care system. A total of 151 patients were advised to stop smoking, and were asked to participate in the program if judged sufficiently motivated by the physicians. After inclusion they were randomized into short or long follow-up, and nicotine gum vs no gum. The physicians conducted the follow-up therapy in their own personal way. Short follow-up was comprised of one appointment 14 days after cessation, while long follow-up consisted of a telephone call (1 week), an appointment (2 weeks), a second appointment (1 month), and a letter (3 months). The results at 12 months were that long follow-up showed a trend (P less than 0.12 toward being better than short follow-up, while nicotine gum was significantly better than no gum (P less than 0.05) in maintaining abstinence. The group with the best outcome was the one receiving long follow-up and nicotine gum, which yielded an expired air carbon monoxide-controlled, 12-month abstinence rate of 27%. The abstinence outcomes at 12 months for the other groups were short follow-up and nicotine gum, 22%; long follow-up and no gum, 15%; and short follow-up and no gum, 3%. The physicians' reactions to the smoking cessation treatment were largely positive. The nicotine gum seems to be a relatively simple, cost-effective, and practical tool for physicians to enhance and reinforce their antismoking advice. With a longer active follow-up period than was used here (1 month), even better results may be possible.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Controlled trial of three different antismoking interventions in general practice.

Of 6052 adult patients who consulted their doctors in six Oxfordshire general practices between October 1980 and February 1981, 2110 (35%) were smokers. The smokers were allocated to one of four study groups--a control (non-intervention) group; a group that received verbal and written antismoking advice from the general practitioner; a group that received this advice and also a demonstration of exhaled carbon monoxide; and a group that received the advice plus the offer of further help from a health visitor. After one year 72% of smokers replied to a postal follow up questionnaire: 11% of the control group claimed to have stopped smoking compared with 15% in the group that received advice alone, 17% in the exhaled carbon monoxide group, and 13% in the health visitor group. Validation of these findings by assays of urinary concentrations of cotinine showed that between 24% and 40% of subjects may have misreported their smoking habits, but there was no indication that the rate of misreporting was higher in the intervention groups than in the control group. Giving advice routinely against smoking has a useful effect, and showing an immediate, personal, and potentially harmful consequence of smoking using a CO-oximeter may improve this, particularly in lower socioeconomic groups.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

The impact of physicians' brief smoking cessation counseling: a MIRNET study.

Although many family physicians may discuss smoking cessation with their patients, few do so consistently. A common belief among many physicians is that such efforts will not deter their patients from smoking. Others believe the time commitment required for a successful intervention is excessive. The present study addressed the above issues by examining the effect of a 3- to 5-minute unstructured physician discussion encouraging smoking cessation with family practice patients. Cigarette-smoking patients of two busy family practices in southeast Michigan were randomly assigned to either a control group receiving routine care or an intervention group receiving, in addition to routine care, smoking cessation counseling from their physician. A third comparison group was drawn from smokers in practices not involved in delivering the intervention. Two hundred thirty-eight patients from the intervention group, 178 from the control group, and 47 from the comparison group were followed up with a telephone interview at 6 months. Intervention group patients made significantly more quit attempts than did those in the control group (P less than .001), which was similar to the comparison group. At the 6-month follow-up, 8% of intervention group members, and 4% of both the comparison and control groups reportedly were abstinent from smoking. Among those contacted at the 1-year follow-up, the respective percentages abstinent were 8%, 3%, and 4%. Although these differences in quit rates were not statistically significant, the findings suggest that physicians can positively affect patient smoking cessation. This intervention was feasible in busy family practices, highlighting its generalizability and applicability to other family practice settings in the United States.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Reducing maternal smoking and relapse: long-term evaluation of a pediatric intervention.

Pediatric well-care visits provide a clinical opportunity to counsel new mothers about their smoking and the deleterious effects of environmental tobacco smoke (ETS) on infant health. Forty-nine Oregon pediatric offices enrolled 2,901 women who were currently smoking or had quit for pregnancy, using a brief survey at the newborn's first office visit. Randomly assigned offices provided advice and materials to mothers at each well-care visit during the first 6 months postpartum to promote quitting or relapse prevention. The intervention reduced smoking (5.9% vs 2.7%) and relapse (55% vs 45%) at 6-month follow-up, but logistic regression analysis at 12 months revealed no significant treatment effect. The intervention had a positive effect on secondary outcome variables, such as readiness to quit and attitude toward and knowledge of ETS. Multiple logistic regression analysis indicated that husband/partner smoking was the strongest predictor of maternal quitting or relapse. A pediatric office-based intervention can significantly affect smoking and relapse prevention for mothers of newborns, but the effect decreases with time. Consistent prompting of the provider to give brief advice and materials at well-care visits could provide a low-cost intervention to reduce infant ETS exposure.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

A family physician smoking cessation program: an evaluation of the role of follow-up visits.

Our purpose in this randomized clinical trial was to compare a two-visit smoking cessation intervention by family physicians with the same intervention supplemented by additional follow-ups. Forty-one southern Ontario family physicians volunteered for the study and subsequently participated in a four-hour training program on smoking cessation techniques. Physicians advised patients who smoked and indicated an interest in attempting to quit with the help of their physician to stop smoking at the end of a regularly scheduled visit. Physicians instructed patients to make a specific appointment for an evaluation of their smoking habits. Six hundred forty-seven patients returned for that assessment and were than randomized into either the two-visit intervention group (with risk assessment, support, the setting of a cessation date, self-help literature, and a prescription for nicotine gum, where appropriate) or into the other intervention group (with the same maneuvers as well as the offer of four more supportive follow-up visits). We found no statistically significant difference in one-year, biochemically validated, sustained cessation rates between the group offered the long-term follow-up visits (12.5%) and the group given the brief intervention (10.2%). The 95% confidence interval on the difference between the groups was 2.8% in favor of the brief intervention group to 7.3% in favor of the group offered follow-up. The results do not support the value of long-term follow-up visits for smokers.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Facilitating autonomous motivation for smoking cessation.

Physicians used either an autonomy-supportive or a controlling interpersonal style to counsel smokers based on National Cancer Institute guidelines. Physician autonomy support was rated from audiotapes, and patients' perceived competence and autonomous motivation for quitting were self-reported on questionnaires. Validated point prevalences for 6, 12, and 30 months and for continuous cessation were examined. The intervention did not have a direct effect on quit rates; however, structural equation modeling supported the self-determination process model of smoking cessation. The model indicated that the autonomy-supportive intervention was rated as more autonomy supportive, that rated autonomy support predicted autonomous motivation, and that autonomous motivation predicted cessation at all points in time. Perceived competence contributed independent variance to cessation only at 6 months.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Randomized controlled trial of a computer-based, tailored intervention to increase smoking cessation counseling by primary care physicians.

The primary care visit represents an important venue for intervening with a large population of smokers. However, physician adherence to the Smoking Cessation Clinical Guideline (5As) remains low. We evaluated the effectiveness of a computer-tailored intervention designed to increase smoking cessation counseling by primary care physicians. Physicians and their patients were randomized to either intervention or control conditions. In addition to brief smoking cessation training, intervention physicians and patients received a one-page report that characterized the patients' smoking habit and history and offered tailored recommendations. Physician performance of the 5As was assessed via patient exit interviews. Quit rates and smoking behaviors were assessed 6 months postintervention via patient phone interviews. Intervention effects were tested in a sample of 70 physicians and 518 of their patients. Results were analyzed via generalized and mixed linear modeling controlling for clustering. Intervention physicians exceeded controls on "Assess" (OR 5.06; 95% CI 3.22, 7.95), "Advise" (OR 2.79; 95% CI 1.70, 4.59), "Assist-set goals" (OR 4.31; 95% CI 2.59, 7.16), "Assist-provide written materials" (OR 5.14; 95% CI 2.60, 10.14), "Assist-provide referral" (OR 6.48; 95% CI 3.11, 13.49), "Assist-discuss medication" (OR 4.72;95% CI 2.90, 7.68), and "Arrange" (OR 8.14; 95% CI 3.98, 16.68), all p values being < 0.0001. Intervention patients were 1.77 (CI 0.94, 3.34,p = 0.078) times more likely than controls to be abstinent (12 versus 8%), a difference that approached, but did not reach statistical significance, and surpassed controls on number of days quit (18.4 versus 12.2, p < .05) but not on number of quit attempts. The use of a brief computer-tailored report improved physicians' implementation of the 5As and had a modest effect on patients' smoking behaviors 6 months postintervention.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

The impact of routine advice on smoking cessation from family physicians.

Cigarette smoking continues to be a major health problem. Therefore, physicians have been asked to advise all their patients on the hazards of smoking. A controlled trial was undertaken to measure the impact of family physicians' advice to cigarette smokers during a routine office visit. No significant differences were found in the three measures used to determine outcome--desire to stop smoking, an attempt to stop and success in stopping--between the control and intervention groups. These results are discussed in relation to the health belief model, and suggestions are made on how to increase the impact family physicians could have on smoking cessation to their practices.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Randomized clinical trial of supportive follow-up for cigarette smokers in a family practice.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Smoking prevention among people aged 60 and over: a randomized controlled trial.

This study aimed to test the hypothesis that people aged 60 and older respond to assistance in stopping smoking. Using a single general practitioner visit backed up by a practice nurse, 14% of the smokers had discontinued the habit 6 months after the intervention period. The intervention group also showed some improvements in a standardized measure of breathlessness.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

[Effectiveness of the physician's advice to quit smoking: evaluation of the impact a year after the fact].

The results of a physician-based intervention on smoking done by general practitioners in Barcelona (Spain) are described one month and one year after its inception. Among the 208 smokers in the intervention group there were more attempts to quit, and they were more successful than in the 216 smokers in the control group. The proportions of quitters after a year was 5.3% and 2.3% in each group (p less than 0.05). Among the variables related to success in quitting are self-reliance, the willingness to reduce or quit smoking, the intensity of the habit and the family environment.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Effect of nicotine chewing gum as an adjunct to general practitioner's advice against smoking.

This study was designed to see whether the offer and prescription of nicotine chewing gum would enhance the efficacy of general practitioners' advice to stop smoking. A sample of 1938 cigarette smokers who attended the surgeries of 34 general practitioners in six group practices were assigned by week of attendance (in a balanced design) to one of three groups: (a) non-intervention controls, (b) advice plus booklet, and (c) advice plus booklet plus the offer of nicotine gum. Follow up was done after four months and one year. The results show a clear advantage for those offered the nicotine gum (p less than 0.001). After correction for those who refused or failed chemical validation and those who switched from cigarettes to a pipe or cigars, the proportions who were abstinent at four months and still abstinent at one year were 3.9%, 4.1%, and 8.8% in the three groups, respectively. These percentages are based on all cigarette smokers who attended the surgeries including those who did not wish to stop and those in the gum group who did not try the gum (47%). The effect of the offer and prescription of gum was to motivate more smokers to try to stop, to increase the success rate among those who tried, and to reduce the relapse rate of those who stopped. The self selected subgroup of 8% who used more than one box of 105 pieces of gum achieved a success rate of 24%. It would be feasible and effective for general practitioners to include the offer of nicotine gum and brief instructions on its use as part of a minimal intervention routine with all cigarette smokers. A general practitioner who adopts such a routine with similar success could expect to achieve about 35-40 long term ex-smokers a year and so save the lives of about 10 of them. If replicated by all general practitioners throughout the country the yield of ex-smokers would be about one million a year.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Smoking cessation in patients with COPD in daily general practice (SMOCC): six months' results.

Chronic Obstructive Pulmonary Disease (COPD) forms an increasing health problem. Despite smoking cessation improving the prognosis of the disease, many patients persist smoking. The present study presents the results of a smoking cessation counseling protocol in general practice (Smoking Cessation in patients with COPD in general practice (SMOCC)). A randomized controlled trial of patients with COPD compared smoking cessation counseling according to an intensified minimal intervention strategy with usual care. In total 43 general practices with 392 patients participated in Nijmegen, The Netherlands, in 2001-2002. Significantly more smokers in the experimental group made a quit attempt (44.9% versus 36.5%) and actually quit smoking than in the control group (16.0% versus 8.8%). The motivation to stop smoking at baseline was not associated with smoking cessation. The SMOCC strategy doubled the self-reported quit rates and was complied well by the general practitioners. Implementation in general practice is recommended.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Effectiveness of a minimal contact smoking cessation program for Dutch general practitioners: a randomized controlled trial.

Until recently, Dutch general practitioners contributed little to tobacco control. This is due to several factors, among which is the lack of a feasible intervention program for adult smokers. Such a minimal contact behavioral intervention, using the Stage-of-Change concept, is now available. Effectiveness was tested in a randomized trial. Twenty-two general practitioners and their practice assistants were trained in applying the program. In all, 530 smoking patients were enrolled, randomly assigned to either the intervention or the usual treatment condition. Analysis of treatment effects was performed with logistic regression analysis. In a backward stepwise procedure confounding effects of baseline differences were eliminated. At 12-month follow-up, self-reported abstinence rates (including nonrespondents as smokers) differed significantly between intervention subjects and controls: 13.4 vs 7.3% point prevalence (odds ratio 1.51, P < 0.05). An analysis of consecutive abstinence, defined as being abstinent at both 6- and 12-month follow-up, showed that 8.2% of the intervention group compared to 3.1% of the controls had sustained abstinence for more than 6 months (odds ratio 3.04, P < 0.001). Results indicate that an effective smoking cessation program for use in Dutch general practice, already shown to be feasible, is now available. Outcomes are generally consistent with recent international literature. Copyright 2001 American Health Foundation and Academic Press.

CD000165

Simple advice has a small effect on cessation rates. Assuming an unassisted quit rate of 2 to 3%, a brief advice intervention can increase quitting by a further 1 to 3%. Additional components appear to have only a small effect, though there is a small additional benefit of more intensive interventions compared to very brief interventions.

Effectiveness of smoking cessation interventions integrated into primary care practice.

Using a complete factorial design, we tested three interventions for smoking cessation in routine primary care practice. The interventions tested were 1) physician counseling, 2) mailed letters and educational materials designed by the National Cancer Institute (NCI), and 3) referral to smoking cessation classes. Thirty-seven family practice physicians at three of Group Health's outpatient facilities participated. Patient participation rates were 95%, and follow-up was complete for 92% of those participating. None of the interventions had any effect on point prevalence of quitting as determined 8-9 months later by self-report. However, the combination of physician counseling and NCI materials doubled the odds of occurrence of significant antismoking behavior (quit, quit and relapse, or cut down) during the ensuing 8-9 months in those individuals receiving that combination. Referral to smoking cessation classes was strikingly ineffective in this setting. Of 369 individuals designated by study design for referral, only 14% even investigated the classes. This compares with a 10% self-referral rate for those persons not designated for referral by our study design. Our results and other recent work suggest that more intensive interventions on multiple occasions based on relapse prevention strategies hold promise for future success in smoking cessation efforts in primary care.

CD007176

We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.

A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study.

Randomized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and, to our knowledge, no previous trial has examined the individual effect of ascorbic acid (vitamin C) on CVD. The Women's Antioxidant Cardiovascular Study tested the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day) on the combined outcome of myocardial infarction, stroke, coronary revascularization, or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design. Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years, from 1995-1996 to 2005. A total of 1450 women experienced 1 or more CVD outcomes. There was no overall effect of ascorbic acid (relative risk [RR], 1.02; 95% CI, 0.92-1.13 [P = .71]), vitamin E (RR, 0.94; 95% CI, 0.85-1.04 [P = .23]), or beta carotene (RR, 1.02; 95% CI, 0.92-1.13 [P = .71]) on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD (RR, 0.89; 95% CI, 0.79-1.00 [P = .04]; P value for interaction, .07). There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes (P value for interaction, .03). There were no overall effects of ascorbic acid, vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD.

CD007176

We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.

A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group.

Increasing evidence suggests that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of paralysis in transgenic mice expressing a mutation in superoxide dismutase found in certain forms of familial ALS. The current study was designed to determine whether alpha-tocopherol (500 mg b.i.d.) may be efficacious in the treatment of ALS. Two hundred and eighty-nine patients with ALS of less than 5 years duration, treated with riluzole, were enrolled in this study, and were randomly assigned to receive either alpha-tocopherol or placebo daily for one year. The primary outcome measure was the rate of deterioration of function assessed by the modified Norris limb scale. Patients were assessed at entry, and every 3 months thereafter during the study period. Survival was also recorded. Biochemical markers of oxidative stress were measured in a subset of patients on entry and after 3 months of treatment. After 12 months of treatment, alpha-tocopherol had no effect on the primary outcome measure. Survival was not influenced by treatment. Among secondary outcome measures, patients given alpha-tocopherol were less likely to progress from the milder state A to the more severe state B (P=0.046) of the ALS Health State scale. After 3 months treatment, analysis of oxidative stress markers showed an increase in glutathione peroxidase activity in plasma (P = 0.0389) and a decrease in plasma levels of thiobarbituric acid reactive species (P = 0.0055) in the group of patients given alpha-tocopherol in combination with riluzole. Although alpha-tocopherol did not appear to affect the survival and motor function in ALS, patients receiving riluzole plus alpha-tocopherol remained longer in the milder states of the ALS Health State scale and showed, after 3 months, changes in biochemical markers of oxidative stress. Further studies are required to confirm the greater sensitivity of the ALS Health State scale over other clinical endpoints.

CD007176

We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.

Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions.

Randomized trials have yielded mixed results on the effects of treatment for Helicobacter pylori and little information on the effects of vitamins or garlic supplements on precancerous gastric lesions. We conducted a randomized trial to test the effects of one-time H. pylori treatment and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions. Most of the adults aged 35-64 years in 13 randomly selected villages in Linqu County, Shandong Province, China, were identified and given baseline endoscopies in 1994. In 1995, 3365 eligible subjects were randomly assigned in a factorial design to three interventions or placebos: amoxicillin and omeprazole for 2 weeks in 1995 (H. pylori treatment); vitamin C, vitamin E, and selenium for 7.3 years (vitamin supplement); and aged garlic extract and steam-distilled garlic oil for 7.3 years (garlic supplement). Subjects underwent endoscopies with biopsies in 1999 and 2003, and the prevalence of precancerous gastric lesions was determined by histopathologic examination of seven standard biopsy sites. The 3365 eligible randomized subjects represented 93.5% of those with baseline endoscopy and included all baseline histologic categories except gastric cancer. Only 0.18% had normal gastric mucosa. Logistic regression was used to estimate the intervention effects on the odds of advanced precancerous gastric lesions, and t-tests were used to assess effects on histologic severity. All statistical tests were two-sided. H. pylori treatment resulted in statistically significant decreases in the combined prevalence of severe chronic atrophic gastritis, intestinal metaplasia, dysplasia, or gastric cancer in 1999 (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.62 to 0.95) and in 2003 (OR = 0.60; 95% CI = 0.47 to 0.75), and had favorable effects on the average histopathologic severity and on progression and regression of precancerous gastric lesions in 2003. H. pylori treatment did not reduce the combined prevalence of dysplasia or gastric cancer. However, fewer subjects receiving H. pylori treatment (19/1130; 1.7%) than receiving placebo (27/1128; 2.4%) developed gastric cancer (adjusted P = .14). No statistically significant favorable effects were seen for garlic or vitamin supplements. H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence, but further data are needed to prove the latter point. Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence.

CD007176

We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.

Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico.

There is conflicting evidence on the benefits of foods rich in vitamin E (alpha-tocopherol), n-3 polyunsaturated fatty acids (PUFA), and their pharmacological substitutes. We investigated the effects of these substances as supplements in patients who had myocardial infarction. From October, 1993, to September, 1995, 11,324 patients surviving recent (< or = 3 months) myocardial infarction were randomly assigned supplements of n-3 PUFA (1 g daily, n=2836), vitamin E (300 mg daily, n=2830), both (n=2830), or none (control, n=2828) for 3.5 years. The primary combined efficacy endpoint was death, non-fatal myocardial infarction, and stroke. Intention-to-treat analyses were done according to a factorial design (two-way) and by treatment group (four-way). Treatment with n-3 PUFA, but not vitamin E, significantly lowered the risk of the primary endpoint (relative-risk decrease 10% [95% CI 1-18] by two-way analysis, 15% [2-26] by four-way analysis). Benefit was attributable to a decrease in the risk of death (14% [3-24] two-way, 20% [6-33] four-way) and cardiovascular death (17% [3-29] two-way, 30% [13-44] four-way). The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint (14% [1-26]) and for fatal events (20% [5-33]). Dietary supplementation with n-3 PUFA led to a clinically important and statistically significant benefit. Vitamin E had no benefit. Its effects on fatal cardiovascular events require further exploration.