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cochrane_sparse_oracle

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[ "Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea.", "Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies.", "Randomized placebo-controlled trial of a flavonoid-rich plant extract-based cream in the treatment of rosacea.", "Comparative effectiveness of tetracycline and ampicillin in rosacea. A controlled trial.", "Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea.", "Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea.", "Combination sodium sulfacetamide 10% and sulfur 5% cream with sunscreens versus metronidazole 0.75% cream for rosacea.", "Comparative efficacy of nonpurpuragenic pulsed dye laser and intense pulsed light for erythematotelangiectatic rosacea.", "A comparison of metronidazole 1% cream and pimecrolimus 1% cream in the treatment of patients with papulopustular rosacea: a randomized open-label clinical trial.", "Permethrin 5% cream versus metronidazole 0.75% gel for the treatment of papulopustular rosacea. A randomized double-blind placebo-controlled study.", "Treatment of rosacea by metronidazole.", "Efficacy of 1% 4-ethoxybenzaldehyde in reducing facial erythema.", "Topical metronidazole therapy for rosacea.", "Treatment of rosacea with i% metronidazole cream. A double-blind study.", "A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea.", "Double-blind comparison of azelaic acid 20% cream and its vehicle in treatment of papulo-pustular rosacea.", "Topical metronidazole in the treatment of rosacea.", "Treatment of rosacea: topical clindamycin versus oral tetracycline.", "Double-blind, randomized, vehicle-controlled clinical trial of once-daily benzoyl peroxide/clindamycin topical gel in the treatment of patients with moderate to severe rosacea.", "Pimecrolimus cream 1% for papulopustular rosacea: a randomized vehicle-controlled double-blind trial.", "Effect of treatment of Helicobacter pylori infection on rosacea.", "A multicenter study of topical azelaic acid 15% gel in combination with oral doxycycline as initial therapy and azelaic acid 15% gel as maintenance monotherapy.", "Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea.", "Combined effect of anti-inflammatory dose doxycycline (40-mg doxycycline, usp monohydrate controlled-release capsules) and metronidazole topical gel 1% in the treatment of rosacea.", "The efficacy of topical metronidazole in the treatment of ocular rosacea.", "A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea.", "Topical metronidazole maintains remissions of rosacea.", "Oral zinc sulfate in the treatment of rosacea: a double-blind, placebo-controlled study.", "Topical treatment of acne rosacea with benzoyl peroxide acetone gel.", "A double-blind study of I% metronidazole cream versus systemic oxytetracycline therapy for rosacea.", "Treatment of facial telangiectasia using a dual-wavelength laser system (595 and 1,064 nm): a randomized controlled trial with blinded response evaluation.", "Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea.", "The efficacy of metronidazole 1% cream once daily compared with metronidazole 1% cream twice daily and their vehicles in rosacea: a double-blind clinical trial.", "A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea.", "Efficacy of topical cyclosporine for the treatment of ocular rosacea.", "Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea.", "A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea.", "[Rilmenidine in rosacea: a double-blind study versus placebo].", "A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial.", "Effect of nadolol on flushing reactions in rosacea.", "Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial.", "An evaluation of a polyhydroxy acid skin care regimen in combination with azelaic acid 15% gel in rosacea patients.", "Comparative study of some treatment modalities of rosacea." ]

[ "The papules and pustules of rosacea can be effectively treated with topical metronidazole. The optimal concentrations of metronidazole and optimum frequencies of application are uncertain. Traditionally, twice-daily applications have been advised, based on the pharmacokinetic profile of metronidazole. Once-daily applications may be safer and less expensive, and they may enhance patient compliance.\n We compared the efficacy and safety of 2 commercially available topical metronidazole formulations (0.75% metronidazole cream formulation and 1.0% metronidazole cream formulation) when both were used in a once-daily regimen.\n A multicenter, randomized, investigator-blind, parallel group trial was conducted at 3 separate clinical sites located in 3 US cities. The study enrolled 72 rosacea patients with at least 8 to 50 inflammatory facial lesions (pustules and papules) and moderately severe facial erythema. Patients were randomly assigned to receive either 0.75% metronidazole cream or 1.0% metronidazole cream and instructed to apply the medication once daily for 12 weeks. Patients' lesions were evaluated at baseline and at weeks 3, 6, 9, and 12.\n There were no significant differences between treatment groups for any of the efficacy parameters evaluated. The overall median percentage change in lesion count at end point for patients in the 0.75% metronidazole cream treatment group was -62% compared with -60% for the 1.0% metronidazole cream treatment group. The overall percentage change in erythema scores at endpoint for patients in the 0.75% metronidazole cream treatment group was -26% compared with -30% for patients in the 1.0% metronidazole cream treatment group. Regarding physician assessment of global severity, 57% of subjects (20/35) in the 0.75% metronidazole cream group compared with 37% of subjects (13/35) in the 1.0% metronidazole cream group were rated as having a clear to mild condition at end point. Both drugs were well tolerated; there was no significant difference in the number of drug-related adverse events between the two agents.\n This controlled trial demonstrates that both 0.75% metronidazole cream and 1.0% metronidazole cream, when used once daily, provide well-tolerated efficacy for moderate to severe rosacea.", "Rosacea is a common, chronic dermatosis for which safe and effective new treatment options are needed.\n The objective of these studies was to evaluate the efficacy, tolerability, and safety of a new formulation of 15% azelaic acid (15%) gel (AzA gel), for the topical treatment of moderate, papulopustular rosacea.\n Two multicenter, double-blind, randomized, parallel-group, vehicle-controlled studies were conducted using identical study designs, patient-selection criteria, and efficacy end points. Overall, 329 patients were enrolled in study 1 and 335 patients in study 2.\n Both studies consistently demonstrated the superiority of AzA gel over vehicle in the topical treatment of moderate, papulopustular rosacea. AzA gel yielded statistically significantly higher reductions in mean inflammatory lesion count than vehicle: 58% versus 40%, study 1 (P =.0001); 51% versus 39%, study 2 (P =.0208). Significantly higher proportions of patients treated with AzA gel experienced improvement in erythema compared with vehicle gel: 44% versus 29%, study 1 (P =.0017); 46% versus 28%, study 2 (P =.0005). Using the investigator's global assessment, therapeutic success in terms of a clear, minimal, or mild final result was achieved in 61% and 62% of patients treated with AzA gel in studies 1 and 2, respectively, which was significantly superior to the result achieved with vehicle (40% and 48%, respectively) (P <.0001, study 1; P =.0127, study 2). No serious, treatment-related adverse events were reported.\n The results of these 2 controlled studies demonstrate that AzA gel, used twice daily, is an efficacious, safe, and well-tolerated topical treatment for moderate, papulopustular rosacea.", "Biological research suggests that vascular changes may play a major role in rosacea pathogenesis. Chrysanthellum indicum is a plant-based extract containing a unique combination of phenylpropenoic acids, flavonoids and saponosids, and has a well-documented effect on vascular wall permeability and increase of the mechanical resistance of capillaries.\n To determine the efficacy and safety of a cream containing 1%C. indicum extract with vitamin P properties in the treatment of rosacea.\n This study included 246 patients diagnosed clinically as having moderate rosacea. Patients were randomly allocated to C. indicum extract-based cream (n = 125) and placebo (n = 121) groups. Patients were advised to apply the products on their face twice a day for a 12-week period. The patients were examined at the end of each 4-week period. Severity of erythema (graded by reference to six photographs), surface of erythema and rosacea overall severity scores were recorded at each visit on days 0, 28, 56 and 84. Investigators carried out a final efficacy assessment at the end of week 12. Volunteers' final overall efficacy assessment was recorded in a self-administered questionnaire. Adverse events were identified through examination, interview and collection of comments in patients' questionnaires.\n Treatment with the C. indicum extract-based cream resulted in significant improvement (P < 0.05) in severity of erythema, overall rosacea severity compared to baseline and placebo, and investigator and patient overall efficacy assessment scores (P = 0.046 and P = 0.001, respectively) compared with placebo scores. Adverse reactions were mild, and did not differ between the C. indicum extract-based cream and the placebo groups.\n Chrysanthellum indicum extract-based cream is an effective and well-tolerated topical agent for the treatment of moderate rosacea. The mode of action of the active ingredient suggests that additional efficacy might be expected from combination with other topical treatments.", "nan", "Rosacea is an inflammatory dermatologic disorder characterized by the presence of facial erythema, visible blood vessels, papules, and pustules. The National Rosacea Society has established a classification system that identifies 4 distinct rosacea subtypes based on clinical presentation: erythematotelangiectatic, papulopustular, phymatous, and ocular. The goal of topical therapy for rosacea is to reduce inflammatory lesion counts; decrease intensity of erythema; and reduce symptoms such as stinging, burning, and pruritus. Metronidazole and azelaic acid are thought to reduce the inflammation associated with rosacea by inhibiting the production of reactive oxygen species produced by neutrophils. Both metronidazole 1% gel and azelaic acid 15% gel recently have been approved for the treatment of rosacea. The current study was conducted to compare the once-daily application of metronidazole 1% gel with twice-daily applications of azelaic acid 15% gel for the treatment of patients with moderate rosacea (N=160). Both treatments showed similar reductions in inflammatory lesion counts (77% for metronidazole 1% gel and 80% for azelaic acid 15% gel) and high success rates in both global severity (53.7% vs 56.4% for metronidazole 1% gel and azelaic acid 15% gel, respectively) and erythema (42.7% vs 42.3% for metronidazole 1% gel and azelaic acid 15% gel, respectively). On average, the efficacy (including reduction in erythema) of the once-daily application of metronidazole 1% gel and twice-daily applications of azelaic acid 15% gel were similar.", "Doxycycline monotherapy at antimicrobial doses has been shown to be effective for the treatment of rosacea.\n To evaluate the efficacy and safety of once-daily anti-inflammatory dose doxycycline for the treatment of rosacea.\n In two phase III, parallel-group, multicenter, randomized, double-blind, placebo-controlled studies (studies 301 and 302), patients received 40-mg of controlled-release doxycycline (n = 269) or placebo (n = 268) for 16 weeks. The primary efficacy end point was the mean change from baseline in facial inflammatory lesion count.\n The mean lesion count at baseline was approximately 20 in each study arm. At week 16, the mean change from baseline in lesion count in the active-treatment groups was -11.8 in study 301 and -9.5 in study 302 compared with -5.9 and -4.3, respectively, in the placebo groups (P < .001 for both comparisons). Anti-inflammatory dose doxycycline was well tolerated; the most common adverse events were nasopharyngitis (4.8%), diarrhea (4.4%), and headache (4.4%).\n In both studies, the reduction of inflammatory lesion counts did not plateau within the 16-week time frame in either treatment group. Rosacea is often treated for a period of months or years. The duration of the studies did not allow for assessment of safety beyond 16 weeks or whether the progressive improvement seen with active treatment would continue beyond 16 weeks. Neither study assessed the effect of treatment in patients with only erythematotelangiectatic (subtype 1) rosacea.\n Once-daily anti-inflammatory dose doxycycline appears to be effective and safe for the treatment of rosacea.", "Topical metronidazole and combination sodium sulfacetamide and sulfur commonly are used to treat rosacea. Recently, the relative efficacy and safety of sodium sulfacetamide 10% and sulfur 5% cream with sunscreens (Rosac Cream) (n = 75) and metronidazole 0.75% cream (Metrocream) (n = 77) were compared in an investigator-blinded, randomized, parallel-group study at 6 sites. After 12 weeks of treatment with sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, there was a significantly greater percentage reduction (80%) in inflammatory lesions compared with metronidazole 0.75% cream (72%)(P = .04), as well as a significantly greater percentage of subjects with improved erythema (69% vs 45%, respectively; P = .0007). In addition, the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group had a significantly greater proportion of subjects with success in global improvement at week 12 compared with the metronidazole 0.75% cream group (79% vs 59%, respectively; P = .01). There was no significant difference between treatment groups in the percentage of subjects with improvement in investigator global severity. Overall tolerance was good or excellent in 85% of subjects in the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group and in 97% of subjects in the metronidazole 0.75% cream group. Seven subjects had poor tolerance to the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, possibly caused by a sulfa drug allergy.", "Erythematotelangiectatic (ET) rosacea is commonly treated with a variety of laser and light-based systems. Although many have been used successfully, there are a limited number of comparative efficacy studies.\n To compare nonpurpuragenic pulsed dye laser (PDL) with intense pulsed light (IPL) treatment in the ability to reduce erythema, telangiectasia, and symptoms in patients with moderate facial ET rosacea.\n Twenty-nine patients were enrolled in a randomized, controlled, single-blind, split-face trial with nonpurpuragenic treatment with PDL and IPL and untreated control. Three monthly treatment sessions were performed with initial PDL settings of 10-mm spot size, 7 J/cm(2), 6-ms pulse duration and cryogen cooling, and initial IPL settings of 560-nm filter, a pulse train of 2.4 and 6.0 ms in duration separated by a 15-ms delay, and a starting fluence of 25 J/cm(2). Evaluation measures included spectrophotometric erythema scores, blinded investigator grading, and patient assessment of severity and associated symptoms.\n PDL and IPL resulted in significant reduction in cutaneous erythema, telangiectasia, and patient-reported associated symptoms. No significant difference was noted between PDL and IPL treatment.\n A series of nonpurpuragenic PDL and IPL treatments in ET rosacea was performed with similar efficacy and safety, and both modalities seem to be reasonable choices for the treatment of ET rosacea.", "There are various treatment options available for rosacea, depending on the subtype, but treatment is still generally unsatisfactory. Some reports have indicated beneficial effects of topical pimecrolimus.\n To compare the efficacy and safety of pimecrolimus 1% cream and metronidazole 1% cream in the treatment of patients with papulopustular rosacea (PR).\n A group of 49 patients with PR was investigated in this single-centre, randomized, open-label study. Patients were randomly assigned treatment with either pimecrolimus 1% cream or metronidazole 1% cream for 12 weeks. Response was evaluated by the inflammatory lesion count, the severity of facial erythema and telangiectasia, Physician's Global Assessment (PGA), and safety and tolerability at baseline and at weeks 3, 6, 9 and 12.\n In total, 48 patients completed the study. Both treatments were very effective in the treatment of PR. There were no significant differences between the treatments in inflammatory lesion counts, overall erythema severity scores and PGA evaluated from baseline to week 12 (P > 0.05). Neither treatment produced any clinically relevant improvement in telangiectasia.\n Pimecrolimus cream is no more efficacious than metronidazole cream in the treatment of PR.", "Permethrin 5% cream used against human ectoparasites suggests that it may be effective in papulopustular rosacea.\n This study included 63 patients diagnosed as having papulopustular rosacea based on the clinical and histological findings. Patients were randomly assigned into permethrin (n = 23), metronidazole (n = 20) and placebo (n = 20) groups. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and Demodex folliculorum were determined. Twenty-three patients were given permethrin 5% cream (Zalvor 5% skin cream, 20 patients metronidazole 0.75% gel (Roza gel and 20 patients placebo cream (Basis cream, in packages looking identical to those of metronidazole and permethrin creams, and were recommended to apply them to their faces twice a day. All patients were also given SPF 20 cream for protection against sunlight. Two months of treatment were planned, and the patients were invited to the clinic for fortnightly controls. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and D. folliculorum were recorded at each visit. The mean scores of erythema and the mean numbers of papules, pustules and D. folliculorum were determined at baseline and on days 15, 30, 45 and 60. Side effects were also detected.\n The effect of permethrin 5% cream on D. folliculorum was superior to that of metronidazole 0.75% gel. The effect of permethrin 5% cream on erythema and papules was found to be more effective than placebo and as effective as metronidazole 0.75% gel. However, it had no effect on telangiectasia, rhinophyma and pustules.\n It can be concluded that the application of permethrin 5% cream twice daily for 2 months can be as effective and reliable as metronidazole in the treatment of rosacea and a greater benefit can be gained when it is combined with other systemic and/or topical treatments.\n Copyright 2002 S. Karger AG, Basel", "A double-blind trial in twenty-nine patients with rosacea showed that, after 6 weeks' treatment, metronidazole was therapeutically superior to a placebo (P less than 0-02). It was particularly effective against papules and pustules. The mode of action of metronidazole and other antibiotics in rosacea is not known.", "Facial erythema is a common postsurgical and dermatologic problem. It is commonly the result of dermal inflammation arising from either a facial surgical procedure, such as laser resurfacing, dermabrasion, or a face peel, or from an underlying dermatologic condition, such as rosacea. Facial erythema is difficult for the dermatologist to treat in both settings because topical corticosteroids cannot be used long term on the thin facial skin and anti-inflammatory oral or topical antibiotics have associated side effects.\n The goal of this pilot study was to evaluate the anti-inflammatory effect of 1% 4-ethoxybenzaldehyde in a rosacea model of facial erythema.\n Thirty subjects with mild to moderate stable rosacea were enrolled in this 4-week, double-blind, vehicle-controlled study. Photographs, investigator assessment, and subject assessment were the efficacy criteria.\n There was a statistically significant reduction in facial erythema (p<.01) in those subjects who used the active for 4 weeks, as well as a statistically significant improvement in uneven skin tone (p<.01) and the overall severity of the disease (p<.01). There was no statistically significant difference in any of these three indices in the vehicle-treated group.\n The results suggest that benzaldehyde-derived anti-inflammatory agents may be useful in reducing facial erythema in a rosacea model.", "Forty patients with rosacea were treated topically with 0.75% metronidazole gel in a randomized split-face double-blind paired-comparison trial. With twice-daily applications, 36.7, 48.5, and 65.1 mean percent reductions in total papules and pustules were noted over baseline at 3, 6, and 9 weeks, respectively, on the side of the face receiving metronidazole therapy. Therapy with vehicle alone produced a maximum mean percent reduction of 14.9 at nine weeks. Erythema also responded but was less improved by the end of nine weeks of therapy. A mild increase in telangiectasia was noted on both actively treated and placebo-treated sides. The gel was locally well tolerated. Only two of 40 patients failed to complete the trial, both because of flares of rosacea (one at two days, and one at five weeks). No systemic symptoms were noted, and no consistent abnormalities were found in the results of laboratory studies (hematology, chemistry, and urinalysis). Topical metronidazole gel therapy appears to be a safe and efficacious therapy in the treatment of moderate to severe rosacea.", "Eighty-one patients with rosacea were treated with either I% metronidazole cream or the cream base as a placebo for two months. The trial was performed double-blind, and the patients were assessed once each month. The variates studied were: (I) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, and (5) patient's opinion. Four patients dropped out of the trial (one treated with metronidazole, three with placebo). In all the variates, I% metronidazole cream proved to be significantly more effective than placebo.", "Forty patients with papulo-pustular rosacea were treated for 12 weeks on a random double-blind basis either with oxytetracycline 250 mg twice daily or with metronidazole 200 mg twice daily. Both drugs produced an improvement which was greater after 12 weeks than after 6 weeks, but there was no significant difference between them. Metronidazole appears to be a safe and effective drug for the treatment of rosacea.", "Previous investigations have indicated that topical azelaic acid has beneficial effects in rosacea. This 3-month randomized, double-blind, multicentre study compared the efficacy and safety of azelaic acid 20% cream with its vehicle, in the treatment of papulo-pustular rosacea. A total of 116 patients were enrolled in the study and medication was applied twice daily. Azelaic acid cream produced significantly greater mean reductions in total inflammatory lesions than did vehicle (azelaic acid: 73.4%; vehicle: 50.6%; (p = 0.011), and erythema severity score (azelaic acid: 47.9%; vehicle: 37.9%; (p = 0.031). Azelaic acid cream treatment also resulted in significantly more favourable overall improvements than vehicle in both physician (p = 0.020) and patient ratings (p = 0.042). Neither azelaic acid cream nor vehicle produced any clinically relevant improvement in telangiectasia. Local adverse events were transient and mainly mild or moderate, and rates were similar for azelaic acid cream (39.5%) and vehicle (38.5%). Burning was the symptom most frequently reported. More than 90% of patients rated the overall local tolerability of their treatment as good or acceptable. In conclusion, azelaic acid 20% cream is effective and well tolerated in the treatment of papulo-pustular rosacea.", "One percent metronidazole in an emollient cream base was compared with 250 mg oral tetracycline taken twice daily for the treatment of seventy-five patients with rosacea. After eight weeks of treatment there was no statistically significant difference between the results of the two treatments. Tetracycline did have a more rapid onset of effect on papules and pustules. Both treatments were well tolerated.", "A new topical antibiotic preparation, clindamycin in a lotion base, was compared with oral tetracycline in the treatment of rosacea. Forty-three patients clinically diagnosed as having rosacea were examined in an investigator-blinded study.\n Patients used topical clindamycin lotion applied twice daily or the usual oral dose of tetracycline hydrochloride (250 mg four times a day for 3 weeks, then 250 mg twice a day for the remaining 9 weeks). Patients' lesions were examined clinically at 3-week intervals over a period of 12 weeks.\n Topical clindamycin treatment produced similar clinical results to oral tetracycline and was superior in the eradication of pustules.\n These results show topical clindamycin in a lotion base to be a safe and effective alternative to oral tetracycline therapy in the treatment of rosacea.", "Systemic antibiotics such as tetracycline are well accepted as effective in treating the inflammatory papular/pustular phase of rosacea but may be associated with systemic side-effects. Few controlled data on the use of topical antibiotics in rosacea are available.\n We evaluated the efficacy and tolerability of a fixed combination of 5% benzoyl peroxide and 1% clindamycin in a topical gel for the treatment of rosacea. Methods This was a 12-week, double-blind, vehicle-controlled, randomized, prospective, parallel-group study in 53 patients with moderate to severe rosacea.\n The mean percentage reduction in papules and pustules from baseline to the end of treatment was 71.3% in the benzoyl peroxide/clindamycin group (n = 26) and 19.3% in the vehicle group (n = 26; P = 0.0056). A significant (P = 0.0141) difference in favor of benzoyl peroxide/clindamycin was evident by the third week of treatment. Severity scores for erythema, papules/pustules, and flushing/blushing decreased more with benzoyl peroxide/clindamycin than with vehicle. Overall rosacea severity, Physician Global Assessment, and Patient's Global Assessment at the end of treatment were all significantly improved with benzoyl peroxide/clindamycin compared with vehicle (P = 0.0101, 0.0026, and 0.0002, respectively). Application site reactions were reported in four patients (14.8%) in the benzoyl peroxide/clindamycin group.\n A once-daily topical application of a combination of 5% benzoyl peroxide and 1% clindamycin is effective and well tolerated in patients with moderate to severe rosacea.", "Rosacea remains difficult to treat, despite many therapeutic options.\n To investigate the effect of pimecrolimus cream 1% (Elidel; Novartis Pharma, Nuremberg, Germany) in the treatment of papulopustular rosacea.\n Forty patients with rosacea (25 men and 15 women, mean age 58 years) were enrolled in a randomized, vehicle-controlled, double-blind study. For 4-8 weeks, patients applied pimecrolimus cream or vehicle twice daily to the involved areas on the face. Rosacea severity score, subjective severity assessment and quality of life assessment were obtained, along with photographic documentation.\n Both treatment groups of 20 patients showed an improvement after 4 weeks. The differences were not significant (P > 0 x 05) with regard to mean absolute values, mean percentage changes from baseline, or mean absolute values as differences from baseline for the total score or scores of the different clinical signs (erythema, papulation, scaling and pustules). In the subjective severity score and the quality of life assessment, there was also no significant difference between pimecrolimus and the vehicle (P > 0 x 05).\n Treatment of rosacea for 4-8 weeks with the topical calcineurin inhibitor pimecrolimus cream 1% was not more efficacious than treatment with the vehicle cream.", "To evaluate the clearing and intensity of symptoms of rosacea 60 days after the treatment of Helicobacter pylori infection.\n Randomized, double-blind, placebo-controlled clinical trial.\n The dermatology section of a large multispecialty clinic in the North Central United States.\n Men and women older than 25 years with active signs of rosacea who tested positive for H pylori with both the rapid whole blood test and the urea breath test.\n Treatment of H pylori infection with 14-day therapy using clarithromycin. 500 mg orally 3 times a day, and omeprazole, 40 mg orally once a day.\n The extent and intensity of rosacea as measured by the number of papules and pustules and the extent and intensity of erythema and telangiectasia.\n Three hundred twenty patients presented with rosacea. For 50 patients, the results of a urea breath test were positive for H pylori, and 44 patients were enrolled in the study. Rosacea abated in almost all patients, but none were cured. Notably, lessening of rosacea for patients treated for H pylori was not significantly better than for the control cohort.\n Rosacea abated in most participants in this study, whether they were in the treatment or the control cohort. There was no statistical difference when the results of active treatment were compared with those of placebo. Treating H pylori infection has no short-term beneficial effect on the symptoms of rosacea to support the suggested causal association between H pylori infection and rosacea.", "This two-phase, multicenter study was undertaken to examine the safety and efficacy of combination therapy with oral doxycycline and topical azelaic acid (AzA) 15% gel in moderate-to-severe papulopustular rosacea and to determine the effect of subsequent maintenance monotherapy with AzA 15% gel alone. In the initial open-label, non-randomized phase of the study, subjects (n=172) received topical AzA 15% gel and oral doxycycline (100 mg), both twice daily, for < or = 12 weeks. In the second, double-blind study phase, subjects who had initially undergone at least four weeks of combination treatment in phase 1 and who achieved > or = 75% inflammatory lesion count reduction (n=136) were randomized to receive either AzA 15% gel or its vehicle twice daily for an additional 24 weeks. Assessments of efficacy were obtained at four-week intervals throughout both phases of the study and included change in inflammatory lesion count, investigator global assessment (IGA) of rosacea severity, and separate assessments of erythema and telangiectasia severity. At the last visit for each phase of the study, the investigator and participant each rated overall improvement, with the participant rating cosmetic acceptability and the investigator rating treatment as \"success\" or \"failure\" based on IGA score. During the second phase of the trial, the rate of relapse -- defined as either a 50% deterioration in the lesion count improvement from phase 1, an increase in erythema intolerable to the subject or maintenance therapy failure as judged by the investigator and/or the subject -- was obtained. Safety assessments were conducted for both phases of the study and included analysis of adverse events (AEs) and a rating of cutaneous tolerability by the subject. By week 12 of the open-label phase of the study, 81.4% of subjects had reached a 75% or greater reduction in inflammatory lesion count, and 64% of patients achieved treatment success. During the second study phase (maintenance phase), AzA 15% gel consistently provided a better maintenance response than vehicle, with maintenance of remission in 75% of patients over the six-month duration of the maintenance phase. Additionally AzA 15% gel showed a statistically significantly lower deterioration in absolute inflammatory lesion counts than did vehicle after 8, 16, 20 and 24 weeks of maintenance therapy. No serious treatment-related AEs were encountered in the study, and 98.5% of subjects were satisfied with the local tolerability of both AzA gel and vehicle.", "Twice-daily azelaic acid (AzA) is the conventional regimen for papulopustular rosacea, but once-daily AzA may be equally effective, with greater convenience and dosing flexibility. In order to test this hypothesis, an exploratory study was conducted.\n The evaluable efficacy population of this 12-week double-blind, parallel-group study included 72 patients and the population that was used to report safety results included 92 patients. Baseline characteristics were comparable between the once-daily and twice-daily study groups. Evaluations were performed at baseline and at weeks 4, 8, and 12.\n No significant difference was found between the once-daily and twice-daily groups at the end of study therapy in mean investigator global assessment (IGA) scores, treatment success, or treatment response. The mean number of inflammatory lesions, the intensity of erythema intensity, and the intensity of telangiectasia at treatment end were likewise not significantly different (P>.205 for all). More than 90% of subjects in each group rated cosmetic acceptability of this AzA gel as satisfactory or better.\n Based on these findings and those of prior studies, once-daily AzA 15% gel can therefore be utilized as a safe, effective, and economical dosing option for the treatment of mild-to-moderate papulopustular rosacea. Once-daily dosing of AzA 15% gel was well accepted by patients and can offer considerable dosing flexibility and convenience for the patient as well as for the dermatologist.", "Research into the pathophysiology of rosacea suggests a central role for inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinases (MMPs). Effective treatments for rosacea, including topical metronidazole and systemic antibiotics, have anti-inflammatory activity, which may be more important than their antimicrobial activity in this setting. Phase III studies have substantiated the efficacy of anti-inflammatory dose doxycycline (40-mg doxycycline monohydrate controlled-release capsules) administered once daily for the treatment of inflammatory lesions of rosacea. Results of a 16-week, randomized, double-blind, placebo-controlled study of anti-inflammatory dose doxycycline plus topical metronidazole gel 1% for mild to moderate rosacea are presented here. At week 12, metronidazole was discontinued and patients continued on either placebo or doxycycline. Combination therapy significantly reduced inflammatory lesion counts as early as week 4 and through week 12 compared to topical metronidazole 1% gel monotherapy. The combined therapy appeared effective and well-tolerated.", "The purpose of the study is to investigate the efficacy of metronidazole topical gel in the treatment of ocular rosacea.\n Ten patients with ocular rosacea were treated prospectively with lid hygiene and topical metronidazole applied to the lid margin in one eye and lid hygiene alone in the fellow eye. The treatment period was 12 weeks. A masked observer graded the ocular findings at the initial visit and at the conclusion of the treatment period. Pretreatment scores were compared with post-treatment scores with respect to ocular surface, eyelid margin, and combined eyelid plus ocular surface.\n Eight of ten treated eyes improved, whereas only five of ten control eyes improved. There was a statistically significant improvement in the eyelid score in both the treated and control groups (P = 0.003, P = 0.025, respectively), but no significant improvement in the ocular surface score in either group. When the pretreatment and post-treatment eyelid and ocular surface scores were combined, there was a significant improvement in the treated eyes but not in the control eyes (P = 0.022, P = 0.10, respectively). No adverse effects of the metronidazole treatment were encountered in this study.\n Metronidazole topical gel may be a safe and effective means of treating rosacea blepharitis.", "Although it is important for physicians to have sufficient clinical data on which to base treatment decisions, little comparative data exist regarding newer treatment modalities for rosacea.\n The goal of the study was to compare the efficacy and safety of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Parameters of patient satisfaction to treatment were also assessed.\n Forty patients with the clinical manifestation of symmetric facial rosacea were investigated in this single-center, double-blind, randomized, contralateral split-face comparison clinical trial.\n After 15 weeks of treatment, both azelaic acid and metronidazole induced significant, albeit equal reductions in the number of inflammatory lesions (pustules and papules). A significantly higher physician rating of global improvement was achieved with azelaic acid. Changes in the rosacea signs and symptoms of dryness, burning, telangiectasia, and itching were equal between treatments. A reduction in erythema tended toward significance with azelaic acid at week 15. A trace amount of stinging on application was noted with azelaic acid; however, such discomfort did not appear to concern patients because their overall impression of azelaic acid was superior to that of metronidazole.\n Azelaic acid 20% cream provides an effective and safe alternative to metronidazole 0.75% cream with the added benefit of increased patient satisfaction.", "Rosacea is a chronic skin disease that requires long-term therapy. Oral antibiotics and topical metronidazole successfully treat rosacea. Because long-term use of systemic antibiotics carries risks for systemic complications and adverse reactions, topical treatments are preferred.\n To determine if the use of topical metronidazole gel (Metrogel) could prevent relapse of moderate to severe rosacea.\n A combination of oral tetracycline and topical metronidazole gel was used to treat 113 subjects with rosacea (open portion of the study). Successfully treated subjects (n = 88) entered a randomized, double-blind, placebo-controlled study applying either 0.75% topical metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo) twice daily (blinded portion of the study).\n Subjects were enrolled at 6 separate sites in large cities at sites associated with major medical centers.\n One hundred thirteen subjects with at least 6 inflammatory papules and pustules, moderate to severe facial erythema and telangiectasia entered the open phase of the study. Eighty-eight subjects responded to treatment with systemic tetracycline and topical metronidazole gel as measured by at least a 70% reduction in the number of inflammatory lesions. These subjects were randomized to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel.\n Subjects were evaluated monthly for up to 6 months to determine relapse rates.\n Inflammatory papules and pustules were counted at each visit. Relapse was determined by the appearance of a clinically significant increase in the number of papules and pustules. Prominence of telangiectases and dryness (roughness and scaling) were also observed.\n In the open phase, treatment with tetracycline and metronidazole gel eliminated all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%) displayed fewer papules and pustules after treatment, and 82 subjects (73%) exhibited less erythema. In the randomized double-blind phase, the use of topical metronidazole significantly prolonged the disease-free interval and minimized recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43 subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39 subjects applying metronidazole gel (P<.05). The metronidazole group had fewer papules and/or pustules after 6 months of treatment (P<.01). Relapse of erythema also occurred less often in subjects treated with metronidazole (74% vs 55%).\n In a majority of subjects studied, continued treatment with metronidazole gel alone maintains remission of moderate to severe rosacea induced by treatment with oral tetracycline and topical metronidazole gel.", "Rosacea is a skin problem not uncommonly encountered world-wide. There is a need for an effective and well-tolerated treatment for this disease.\n To evaluate the efficacy and side-effects of zinc sulfate in rosacea in a randomized, controlled, double-blind trial.\n Patients with rosacea who attended the outpatient Clinic of Dermatology and Venereology in Baghdad Teaching Hospital were recruited into this study between October 2002 and August 2004. A disease severity score was calculated for each patient. The patients were randomly allocated to receive either zinc sulfate 100 mg or identical placebo capsules three times per day. Zinc sulfate and placebo capsules were given in a double-blind manner. Following 3 months of starting the treatment, the patients crossed over, i.e. patients on placebo crossed over to zinc sulfate and those on zinc sulfate crossed over to placebo.\n Twenty-five patients with rosacea were included in this study: 16 (64%) females and nine (36%) males. Nineteen patients completed the study: 11 (58%) females and eight (42%) males. Patient age ranged from 21 to 64 years with a mean +/- SD of 48.2 +/- 9.3 years. Duration of the disease ranged from 1 to 14 years with a mean +/- SD of 4.4 +/- 3.2 years. In the group started on zinc sulfate, the score before therapy ranged from 5 to 11 with a mean +/- SD of 8 +/- 2.0. The mean started to decrease directly after the first month of therapy with zinc sulfate to a significantly lower level. After shifting to placebo treatment, the mean started to rise gradually in the fifth month but remained significantly lower than the levels before therapy. In the group started on placebo, the score before therapy ranged from 5 to 9 with a mean +/- SD of 7 +/- 1.3. The mean remained high in the first 3 months of therapy while the patients were on placebo. After shifting to zinc sulfate, the mean started to decrease after the fourth month to significantly low levels. No important side-effects were reported apart from mild gastric upset in three (12%) patients on zinc sulfate.\n Zinc sulfate was found to be a good option in the treatment of rosacea, as it was safe, effective and lacking important side-effects.", "A group of patients with acne rosacea was treated with 5 percent benzoyl peroxide acetone gel for four weeks and then with 10 percent benzoyl peroxide acetone gel for an additional four weeks. A parallel group of patients was treated with a matching placebo (acetone gel vehicle). At the end of the first four weeks of treatment the dropout rate due to lack of improvement was 23 and 63 percent for benzoyl peroxide acetone gel and placebo, respectively. Benzoyl peroxide acetone gel was superior to placebo with respect to improvement in the overall severity of the lesions when judged by photographs, and by reduction of erythema, papules, and pustules. Results after treatment with benzoyl peroxide acetone gel were better during weeks five to eight than during weeks one to four for all lesions except telangiectasia. Benzoyl peroxide acetone gel was superior to placebo when the overall responses were compared. In addition, the benzoyl peroxide acetone gel-treated group, but not the placebo-treated group, showed a significantly better response during weeks five to eight compared to weeks one to four.", "In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either I% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments.", "Pulsed dye (PDL) 595- and 1,064-nm Nd:YAG lasers are used for the treatment of vascular lesions. PDL-heated blood exhibits increased absorption of radiation at 1,064 nm, suggesting that the use of combined sequential dual wavelengths may offer benefits over single-wavelength treatments. This study compares the treatment efficacy of combined sequential dual-wavelength versus single delivery of 595-nm PDL or 1,064-nm Nd:YAG wavelengths in facial telangiectasia in a split face study design using subpurpuric parameters.\n Twenty patients were studied using the sequential delivery of PDL and Nd:YAG wavelengths on one side of the nose. The other side received either PDL or Nd:YAG treatment. Vessels (<0.6 mm in diameter) were treated with a 7-mm spot size at 10 J/cm(2), 10 ms with the PDL, followed by the Nd:YAG at 70 J/cm(2), 15 ms with a multiplex interpulse delay of 100 ms. Subjects received a single treatment, and results were evaluated after 4-week follow-up. Improvement was determined by blinded assessment of photographs taken before and after final evaluation.\n The efficacy of the dual-wavelength laser treatment when compared to Nd:YAG or PDL laser alone was significantly more evident than either single-wavelength treatment (p<.05). There was no statistically significant difference in efficacy between the single-wavelength treatment groups.\n The sequential delivery of 595- and 1,064-nm-wavelength radiation with an interpulse delay suggests that the synergistic approach to laser therapy for facial telangiectasia is a superior method compared to standard single wavelength therapy.", "nan", "nan", "Subantimicrobial doses of doxycycline may improve outcomes in rosacea when combined with topical metronidazole and used as maintenance monotherapy.\n The purpose of this study was to evaluate the safety and efficacy of doxycycline hyclate 20 mg (subantimicrobial dose doxycycline) administered twice daily as an adjunct to metronidazole 0.75% topical lotion in the treatment of rosacea.\n Patients received subantimicrobial doses of doxycycline twice daily plus metronidazole (n = 20) or placebo plus metronidazole (n = 20) for 12 weeks. Subantimicrobial-dose doxycycline or placebo monotherapy continued for 4 weeks. The primary efficacy measure was change from baseline in total inflammatory lesions at weeks 2 and 16.\n Total inflammatory lesions were reduced significantly (P =.048) by week 4 and by all subsequent visits in the subantimicrobial-dose doxycycline/metronidazole group compared with placebo/metronidazole. Changes from baseline increased over time and were maintained during subantimicrobial-dose doxycycline monotherapy.\n Adjunctive use of subantimicrobial dose doxycycline significantly reduced the clinical signs of rosacea compared with metronidazole alone and may be useful maintenance monotherapy.", "This study was designed to compare the efficacy of cyclosporine ophthalmic emulsion 0.05% with an artificial tear solution for the treatment of rosacea-associated eyelid and corneal pathology.\n Double-masked, randomized, 3-month clinical trial of 37 patients with rosacea-associated eyelid and corneal changes (defined as lid margin telangiectasia, meibomian gland inspissation, and/or fullness of the lid margin). All findings were standardized and compared to photographs for grading.\n There was a statistically significant increase in Schirmer (with anesthesia) scores of 2.7+/-2.2 mm after 3 months of treatment in the topical cyclosporine group (P<0.001), compared with a mean decrease of -1.4+/-4.6 mm (P=0.271) in the artificial tears group. The mean tear break-up time score significantly improved in the topical cyclosporine group (mean increase of 3.56+/-1.5 seconds, P<0.001), but worsened in the control group, although this change was not significantly significant (mean decrease of -0.04+/-1.6 seconds, P=0.929). The topical cyclosporine group exhibited a significantly greater mean reduction in corneal staining scores (-1.3+/-0.53) compared with the control group (-0.2+/-0.83; between groups P<0.001). The topical cyclosporine group had a greater improvement in Ocular Surface Disease Index scores than those using artificial tears (P=0.022). Limitations of the study included an older, predominantly Caucasian patient population and short trial length.\n Topical cyclosporine 0.05% is more effective than artificial tears for the treatment of rosacea-associated lid and corneal changes.", "Rosacea is a photoaggravated dermatosis responsive to treatment with topical and oral antibiotics. A formulation combining metronidazole 1% cream with sunscreen SPF 15 was developed for the treatment of rosacea.\n The objective of this study was to determine the safety and efficacy of a formulation combining metronidazole 1% cream with sunscreen SPF 15 in the treatment of moderate to severe rosacea.\n One hundred and twenty patients with moderate to severe rosacea were enrolled for a randomized, placebo-controlled (vehicle containing sunscreen with SPF 15), double-blind study. Study cream was applied twice daily to the entire face over a 12-week period.\n Treatment with metronidazole 1% cream with sunscreen SPF 15 resulted in significant improvement (p <0.05) in inflammatory lesion count, erythema and telangiectasiae scores, and investigator and patient global assessment scores compared with baseline and placebo. Adverse reactions related to study medication were typically mild, occurred at the site of application, and were reversible. There was no difference between the safety profiles of metronidazole 1% cream with sunscreen SPF 15 and placebo.\n The combined topical formulation of metronidazole 1% cream with sunscreen SPF 15 was an effective, well-tolerated topical agent for the treatment of moderate to severe rosacea.", "The efficacy and safety of a new formulation of metronidazole 1 percent cream applied once daily was compared to vehicle cream in a double-blind, randomized, parallel group, ten-week clinical study. The results showed that metronidazole 1 percent cream was significantly better than vehicle in reducing the lesions of rosacea, improving erythema, and physician's global rosacea scores. The incidence of adverse events related to the skin was low.", "The usual treatments of rosacea (cyclines and metronidazole) are mainly effective on reducing the number of papules and pustules. Clonidine only was employed in order to treat flushes observed in rosacea. Rilmenidine is a central hypotensive drug which acts more specifically than clonidine on imidazoline receptors and which has no sedative side effects. The purpose of this study was to evaluate the efficacy of rilmenidine 1 mg/d in the treatment of rosacea.\n A total of 41 patients suffering from typical rosacea were selected in this randomised double blind study rilmenidine versus placebo. The study comprised an 1-month observation period without treatment followed by 3 months of treatment. The major assessment criteria was the proportion of responders at the end of the treatment period. Responders were defined as patients showing a decrease of more than 50 p. 100 in the count of papules and pustules. Minor criterias were the variation of the number of flushes, self-evaluated by the patient and the variation of the redness of the face, noted by the investigator on a scale from 0 to 5.\n Fifteen patients treated by rilmenidine (R) and 19 patients receiving the placebo (P) were evaluated. The proportion of responders was 69.2 p. 100 in group R and 57.1 p. 100 in group P (p = 0.69). The variations of the number of papules and pustules and of the redness of the face were not significantly different in the two groups. The decrease in the number of flushes was higher in group R (around -13) than in group P (around -5), but the difference was not really significant (p = 0.076). Arterial pressure decreased in 3 patients in group R and in 2 patients in group P. Minor side effects were noted in a similar proportion of patients in the two groups.\n Rilmenidine is not efficient in reducing the number of papules and pustules but could decrease the number of flushes. Nevertheless, many patients were lost for follow-up and because of a major placebo effect, the conclusions of this study are not strong enough. Another study including more patients and using evaluation criteria based on the vascular components of rosacea could perhaps confirm this hypothesis.", "To compare the efficacy and safety of a novel formulation of 15% azelaic acid gel (Finacea; Berlex Laboratories, Inc, Montville, NJ) with 0.75% metronidazole gel (MetroGel; Galderma Laboratories LP, Fort Worth, Tex) as topical therapy for moderate, papulopustular facial rosacea.\n Multicenter, double-blind, randomized, parallel-group study.\n Thirteen US centers.\n A total of 251 patients with papulopustular rosacea with persistent erythema and telangiectasia.\n Patients were randomized to receive azelaic acid gel or metronidazole gel twice daily for 15 weeks.\n Nominal and percent change in inflammatory lesion count, change in erythema and telangiectasia severity ratings, investigator's global assessment of rosacea, and investigator's and patient's overall improvement ratings.\n Azelaic acid gel was superior to metronidazole gel in reduction of mean nominal lesion count (-12.9 vs -10.7, respectively) (P =.003) and mean percent decrease in inflammatory lesions (-72.7% vs -55.8%, respectively) (P<.001). With respect to erythema severity, 56% of azelaic acid gel-treated patients were rated improved vs 42% of metronidazole gel-treated patients (P =.02). The effectiveness of metronidazole gel on these variables seemed to plateau after week 8, whereas azelaic acid gel demonstrated progressive improvement through week 15. Neither treatment had a clinically appreciable effect on telangiectasia. Both the investigator's global assessment (P =.02) and overall assessment of improvement (P =.005) showed a significant therapeutic advantage for azelaic acid gel. Azelaic acid gel also scored higher on the patient's overall assessment of efficacy. Both treatments were rated as having high cosmetic acceptability. No serious or systemic treatment-related adverse events were reported in either group.\n Use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea (inflammatory lesions and erythema).", "The effect of nadolol versus placebo on both flushing provoked in a laboratory setting and spontaneous flushing was studied in 15 patients with erythematous telangiectatic rosacea. The intensity of the flushing reactions was assessed in the laboratory by the cutaneous perfusion index method with laser-Doppler velocimetry. No effect of nadolol on the flushing reactions provoked in the laboratory was detected.", "Rosacea is a common inflammatory disorder of the skin. Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side effects. Therefore, a need for an effective agent with few side effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne.\n For evaluation of the efficacy of azithromycin in the treatment of rosacea, we planned a randomized, open, clinical trial study to compare the efficacy of azithromycin with doxycycline in the treatment of this disease. Sixty-seven patients were randomized to receive either azithromycin 500 mg thrice weekly (on Monday, Wednesday, and Saturday) in the first, 250 mg thrice weekly (on Monday, Wednesday, and Saturday) in the second, and 250 mg twice weekly (on Tuesday, and Saturday) in the third month. The other group was given doxycycline 100 mg/day for the three months. Clinical assessment was made at baseline, at the end of first, second, third, and 2 months after treatment. Side affects were recorded. The limitation of this study is that there was no blindness.\n Statistically significant improvement was obtained with both drugs. Neither drug was shown to be more effective than the other. In the azithromycin group four patients had diarrhea, while epigastric burning was seen in two patients using doxycycline.\n This study indicates that azithromycin is at least as effective as doxycycline in the treatment of rosacea.", "nan", "Rosacea is a disease of complex pathogenesis and variable response to various therapeutic methods. Aim of the work To evaluate and compare the efficacy, safety and side effects of some topical lines of treatment of rosacea.\n The study included 24 patients (23 females and 1 male) with rosacea on the face. They were classified into three groups--each including eight patients (16 face sides)--and treated with one of three topical agents (azelaic acid 20% cream, metronidazole 0.75% cream or permethrin 5% cream) on one side of the face and another one on the other side twice daily for 15 weeks.\n There was a significant improvement of lesions after 15 weeks of topical treatment with the three agents. Azelaic acid cream was significantly more effective on inflammatory lesions but not erythema than the other two creams. Side effects--mostly transient--were observed with topical creams with no significant difference. They included itching, burning sensation, oedema and scales. Patients who used azelaic acid 20% cream were more satisfied than with other modalities.\n Azelaic acid 20% cream provides an effective and safe alternative to metronidazole 0.75% cream or permethrin 5% cream with the added benefit of increased patient satisfaction." ]

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[ "Canary in a coal mine? Interest in bupropion SR use among smokers in the COMPASS trial.", "Toward evidence-based Internet interventions: A Spanish/English Web site for international smoking cessation trials.", "Web-based support as an adjunct to group-based smoking cessation for adolescents.", "The RealU online cessation intervention for college smokers: a randomized controlled trial.", "Design and pilot evaluation of an internet smoking cessation program.", "Randomized controlled trial of a web-based computer-tailored smoking cessation program as a supplement to nicotine patch therapy.", "Evaluation of an Internet virtual world chat room for adolescent smoking cessation.", "Web-based smoking-cessation programs: results of a randomized trial.", "Randomized clinical trial of an Internet-based versus brief office intervention for adolescent smoking cessation.", "Comparing internet assistance for smoking cessation: 13-month follow-up of a six-arm randomized controlled trial.", "A randomised control study of a fully automated internet based smoking cessation programme.", "Effect of adding a virtual community (bulletin board) to smokefree.gov: randomized controlled trial.", "Comparing the efficacy of two Internet-based, computer-tailored smoking cessation programs: a randomized trial.", "International Spanish/English Internet smoking cessation trial yields 20% abstinence rates at 1 year.", "Comparing two web-based smoking cessation programs: randomized controlled trial.", "Efficacy of a single computer-tailored e-mail for smoking cessation: results after 6 months.", "Effectiveness of smoking cessation self-help materials in a lung cancer screening population.", "Smoking cessation via the internet: a randomized clinical trial of an internet intervention as adjuvant treatment in a smoking cessation intervention.", "Happy ending: a randomized controlled trial of a digital multi-media smoking cessation intervention.", "A digital smoking cessation program delivered through internet and cell phone without nicotine replacement (happy ending): randomized controlled trial." ]

[ "nan", "The Internet provides a medium to administer and evaluate evidence-based interventions for highly prevalent public health problems worldwide. The authors report a series of four Internet smoking cessation studies conducted in English and Spanish. These studies examined both outcome (self-reported 7-day abstinence) and mechanisms related to outcome (the impact of major depressive episodes [MDEs] on the likelihood of quitting). Over 4,000 smokers from 74 countries entered the studies. Studies 1 and 2 evaluated a standard smoking cessation guide (the \"Guía\"). Studies 3 and 4 were randomized trials comparing the Guía+ITEMs (individually timed educational messages) to the Guía+ITEMs+a mood management course. ITEMs were E-mails inviting participants back to the site at specific times. Online follow-up assessments resulted in completion rates of 44%-54% at 1 month and 26%-30% at 6 months in studies 1 and 2. Incentives and follow-up phone calls increased these rates to 70%, 66%, 65%, and 62% at 1, 3, 6, and 12 months in study 4. At 6 months, self-reported 7-day abstinence rates using missing = smoking data were 6% in studies 1 and 2, 10%-14% in study 3, and 20%-26% in study 4. The Guía+ITEMs condition tended to have higher quit rates, which reached significance at the 12-month follow-up in study 3 and at the 3-month follow-up in study 4. Smokers with past (but not current) MDEs tended to be the most likely to abstain and those with current MDEs the least likely. This trend reached significance in studies 1 and 4.", "Although group-based programs remain the most common treatment approach for adolescent smoking cessation, success rates for these programs have been relatively modest, and their reach may be limited. Web-based adjuncts may be one way to boost the efficacy and reach of group-based approaches. The purpose of this study was to evaluate the effectiveness of enhancing the American Lung Association's Not on Tobacco program (NOT) with a Web-based adjunct (NOT Plus). Twenty-nine high schools were randomly assigned to either the NOT program alone or to the NOT Plus condition, which included access to a specially designed Web site for teens, along with proactive phone calls from the group facilitator to the participant. Self-reported smoking behavior was obtained at end-of-program and at a 3-month follow-up. Using hierarchical linear modeling, accounting for the clustering of students in schools, and controlling for student gender, grade, race, and baseline smoking rate, there was a marginally significant (p=.06) condition effect at end-of-treatment and a significant effect at 3-month follow-up (p<.05) favoring the NOT Plus condition. Approximately 57% of adolescents reported visiting the Web site, and among the NOT Plus condition, use of the Web site was associated with cessation significantly at end-of-program (p<.05), but not at 3 months. Adolescents in urban schools were more likely to access the Web site than those in rural schools. Participants who visited the Web site rated it positively on several dimensions. Reasons for not using the Web site will be discussed, as well as its value as an adjunct.", "To determine the efficacy of providing online cessation intervention for college smokers.\n This is a two-group randomized controlled trial. The intervention group received $10 weekly incentives to visit an online college life magazine that provided personalized smoking cessation messages and peer email support. Evaluation assessments occurred at baseline and 8, 20, and 30 weeks after enrollment. The primary outcome is self-reported 30-day abstinence at week 30. Carbon monoxide (CO) breath testing was performed for participants reporting 30-day abstinence at week 30.\n Five-hundred and seventeen college smokers at the University of Minnesota were enrolled via internet health screening (control=260, intervention=257) in the fall of 2004. Intervention participants completed an average of 18.9 (SD 2.5) of 20 weekly website visits over the course of the study. The rate of 30-day abstinence at week 30 was higher for the intervention compared to the control group (41% vs. 23%, p<0.001). CO testing showed low rates of under-reporting. There was no difference in self-reported 6-month prolonged abstinence measured at week 30.\n Providing personalized smoking cessation messages as part of a general interest online college life magazine increased 30-day abstinence by the end of this two semester intervention.", "Relatively little is known about how to use the Internet to promote health behavioral change. This article describes a multiple-contact Internet smoking cessation program with an 8-week web-based course, online tools for self-monitoring of behaviors, and computer-tailored e-mail messages timed to enrollees' quit efforts. In a pilot study in 49 smokers, we found that enrollees returned to the website a median of 2 times and completed an average of 2 of 8 educational modules. In follow-up, respondents (n = 26) rated e-mail and web components of the intervention as equally valuable (5.9 vs. 5.5 of 10, p = 0.44). While site had potentially important effects on smoking behaviors (34% of enrollees either quit smoking or had a 50% reduction in cigarette use), we were not able hold the interest of the majority of enrollees over the intervention period. Problems with the design of the site are discussed.", "To assess the efficacy of World Wide Web-based tailored behavioral smoking cessation materials among nicotine patch users.\n Two-group randomized controlled trial.\n World Wide Web in England and Republic of Ireland.\n A total of 3971 subjects who purchased a particular brand of nicotine patch and logged-on to use a free web-based behavioral support program.\n Web-based tailored behavioral smoking cessation materials or web-based non-tailored materials.\n Twenty-eight-day continuous abstinence rates were assessed by internet-based survey at 6-week follow-up and 10-week continuous rates at 12-week follow-up.\n Using three approaches to the analyses of 6- and 12-week outcomes, participants in the tailored condition reported clinically and statistically significantly higher continuous abstinence rates than participants in the non-tailored condition. In our primary analyses using as a denominator all subjects who logged-on to the treatment site at least once, continuous abstinence rates at 6 weeks were 29.0% in the tailored condition versus 23.9% in the non-tailored condition (OR = 1.30; P = 0.0006); at 12 weeks continuous abstinence rates were 22.8% versus 18.1%, respectively (OR = 1.34; P = 0.0006). Moreover, satisfaction with the program was significantly higher in the tailored than in the non-tailored condition.\n The results of this study demonstrate a benefit of the web-based tailored behavioral support materials used in conjunction with nicotine replacement therapy. A web-based program that collects relevant information from users and tailors the intervention to their specific needs had significant advantages over a web-based non-tailored cessation program.", "The goal of this longitudinal study was to test an innovative approach to smoking cessation that might be particularly attractive to adolescent smokers. The study was a participatory research effort between academic and school partners. The intervention used an Internet-based, virtual reality world combined with motivational interviewing conducted in real-time by a smoking cessation counselor. Participants were 136 adolescent smokers recruited from high schools randomized to the intervention or a measurement-only control condition. Those who participated in the program were significantly more likely than controls to report at the immediate post-intervention assessment that they had abstained from smoking during the past week (p<or=.01), smoked fewer days in the past week (p<or=.001), smoked fewer cigarettes in the past week (p<or=.01), and considered themselves a former smoke (p<or=.05). Only the number of times quit was statistically significant at a one-year follow-up assessment (p<or=.05). The lack of longer-term results is discussed, as are methodological challenges in conducting a cluster-randomized smoking cessation study.", "Initial trials of web-based smoking-cessation programs have generally been promising. The active components of these programs, however, are not well understood. This study aimed to (1) identify active psychosocial and communication components of a web-based smoking-cessation intervention and (2) examine the impact of increasing the tailoring depth on smoking cessation.\n Randomized fractional factorial design.\n Two HMOs: Group Health in Washington State and Henry Ford Health System in Michigan.\n 1866 smokers.\n A web-based smoking-cessation program plus nicotine patch. Five components of the intervention were randomized using a fractional factorial design: high- versus low-depth tailored success story, outcome expectation, and efficacy expectation messages; high- versus low-personalized source; and multiple versus single exposure to the intervention components.\n Primary outcome was 7 day point-prevalence abstinence at the 6-month follow-up.\n Abstinence was most influenced by high-depth tailored success stories and a high-personalized message source. The cumulative assignment of the three tailoring depth factors also resulted in increasing the rates of 6-month cessation, demonstrating an effect of tailoring depth.\n The study identified relevant components of smoking-cessation interventions that should be generalizable to other cessation interventions. The study also demonstrated the importance of higher-depth tailoring in smoking-cessation programs. Finally, the use of a novel fractional factorial design allowed efficient examination of the study aims. The rapidly changing interfaces, software, and capabilities of eHealth are likely to require such dynamic experimental approaches to intervention discovery.", "Evaluation of novel treatment delivery methods, such as the Internet are notably absent from the adolescent smoking treatment literature.\n Adolescent smokers ages 11-18 years were randomized to a clinic-based, brief office intervention (BOI; N=69) consisting of four individual counseling sessions; or to Stomp Out Smokes (SOS), an Internet, home-based intervention (N=70). Adolescents in SOS had access to the SOS site for 24 weeks.\n The 30-day, point-prevalence smoking abstinence rates for BOI and SOS were 12% versus 6% at week 24 and 13% versus 6% at week 36, with no significant treatment differences. Among participants who continued to smoke, SOS was associated with a significantly greater reduction in average number of days smoked than BOI (P=0.006). The BOI was found to be feasible with high session attendance rates. SOS participants accessed the site a mean+/-S.D. of 6.8+/-7.1 days. SOS use dropped to less than one-third of participants by week 3.\n Additional research is needed to tap the potential capabilities of the Internet for adolescent smoking cessation using proactive, personalized, patient-education components.\n Augmenting the SOS type of intervention with more structured, personal and proactive patient-education components delivered in-person or by telephone or electronic mail is recommended.", "Although many smokers seek Internet-based cessation assistance, few studies have experimentally evaluated long-term cessation rates among cigarette smokers who receive Internet assistance in quitting.\n The purpose of this study is to describe long-term smoking cessation rates associated with 6 different Internet-based cessation services and the variation among them, to test the hypothesis that interactive and tailored Internet services yield higher long-term quit rates than more static Web-posted assistance, and to explore the possible effects of level of site utilization and a self-reported indicator of depression on long-term cessation rates.\n In 2004-05, a link was placed on the American Cancer Society (ACS) website for smokers who wanted help in quitting via the Internet. The link led smokers to the QuitLink study website, where they could answer eligibility questions, provide informed consent, and complete the baseline survey. Enrolled participants were randomly assigned to receive emailed access to one of five tailored interactive sites provided by cooperating research partners or to a targeted, minimally interactive ACS site with text, photographs, and graphics providing stage-based quitting advice and peer modeling.\n 6451 of the visitors met eligibility requirements and completed consent procedures and the baseline survey. All of these smokers were randomly assigned to one of the six experimental groups. Follow-up surveys done online and via telephone interviews at approximately 13 months after randomization yielded 2468 respondents (38%) and found no significant overall quit rate differences among those assigned to the different websites (P = .15). At baseline, 1961 participants (30%) reported an indicator of depression. Post hoc analyses found that this group had significantly lower 13-month quit rates than those who did not report the indicator (all enrolled, 8% vs 12%, P < .001; followed only, 25% vs 31%, P = .003). When the 4490 participants (70%) who did not report an indicator of depression at baseline were separated for analysis, the more interactive, tailored sites, as a whole, were associated with higher quitting rates than the less interactive ACS site: 13% vs 10% (P = .04) among 4490 enrolled and 32% vs 26% (P = .06) among 1798 followed.\n These findings show that Internet assistance is attractive and potentially cost-effective and suggest that tailored, interactive websites may help cigarette smokers who do not report an indicator of depression at baseline to quit and maintain cessation.", "The objective of this project was to test the short term (90 days) efficacy of an automated behavioural intervention for smoking cessation, the \"1-2-3 Smokefree\" programme, delivered via an internet website.\n Randomised control trial. Subjects surveyed at baseline, immediately post-intervention, and 90 days later.\n The study and the intervention occurred entirely via the internet site. Subjects were recruited primarily via worksites, which referred potential subjects to the website.\n The 351 qualifying subjects were notified of the study via their worksite and required to have internet access. Additionally, subjects were required to be over 18 years of age, smoke cigarettes, and be interested in quitting smoking in the next 30 days. Eligible subjects were randomly assigned individually to treatment or control condition by computer algorithm.\n The intervention consisted of a video based internet site that presented current strategies for smoking cessation and motivational materials tailored to the user's race/ethnicity, sex, and age. Control subjects received nothing for 90 days and were then allowed access to the programme.\n The primary outcome measure was abstinence from smoking at 90 day follow up.\n At follow up, the cessation rate at 90 days was 24.1% (n = 21) for the treatment group and 8.2% (n = 9) for the control group (p = 0.002). Using an intent-to-treat model, 12.3% (n = 21) of the treatment group were abstinent, compared to 5.0% (n = 9) in the control group (p = 0.015).\n These evaluation results suggest that a smoking cessation programme, with at least short term efficacy, can be successfully delivered via the internet.", "Demand for online information and help exceeds most other forms of self-help. Web-assisted tobacco interventions (WATIs) offer a potentially low-cost way to reach millions of smokers who wish to quit smoking and to test various forms of online assistance for use/utilization and user satisfaction.\n Our primary aim was to determine the utilization of and satisfaction with 2 versions of a smoking cessation website (smokefree.gov), one of which included an asynchronous bulletin board (BB condition). A secondary goal was to measure changes in smoking behavior 3 months after enrollment in the study.\n All participants were adult federal employees or contractors to the federal government who responded to an email and indicated a willingness to quit smoking in 30 days. We randomly assigned participants to either the BB condition or the publicly available version--usual care (UC)--and then assessed the number of minutes of website use and satisfaction with each condition as well as changes in smoking behavior.\n Among the 1375 participants, 684 were randomized to the BB intervention, and 691 to the control UC condition. A total of 39.7% returned a follow-up questionnaire after 3 months, with similar rates across the two groups (UC: n=279, 40.3%; BB: n=267, 39.0%). Among those respondents assigned to the BB condition, only 81 participants (11.8%) elected to view the bulletin board or post a message, limiting our ability to analyze the impact of bulletin board use on cessation. Satisfaction with the website was high and did not differ significantly between conditions (UC: 90.2%, BB: 84.9%, P= .08). Utilization, or minutes spent on the website, was significantly longer for the BB than the UC condition (18.0 vs 11.1, P = .01) and was nearly double for those who remained in the study (21.2) than for those lost to follow-up (9.6, P< .001). Similar differences were observed between those who made a serious quit attempt versus those who did not (22.4 vs 10.4, P= .02) and between those with a quit date on or a few days prior to the enrollment date versus those with a later quit date (29.4 vs 12.5, P = .001). There were no statistically significant differences in quit rates between the BB and UC group, both in intent-to-treat analysis (ITT) and in analyzing the adherence subgroup (respondents) only. Combined across the UC and BB groups, 7-day abstinence was 6.8% with ITT and 17.6% using only participants in the follow-up (adherence). For participants who attempted to quit within a few days of study entry (vs 30 days), quit rates were 29.6% (ITT) and 44.4% (adherence).\n Quit rates for participants were similar to other WATIs, with the most favorable outcomes demonstrated by smokers ready to quit at the time of enrolling in the trial and smokers using pharmacotherapy. Utilization of the asynchronous bulletin board was lower than expected, and did not have an impact on outcomes (quit rates). Given the demand for credible online resources for smoking cessation, future studies should continue to evaluate use of and satisfaction with Web features and to clarify results in terms of time since last cigarette as well as use of pharmacotherapy.", "Online computer-tailored smoking cessation programs have not yet been compared directly.\n To compare the efficacy of two Internet-based, computer-tailored smoking cessation programs.\n Randomized controlled trial conducted in 2003-2004. Visitors to a smoking cessation website were randomly assigned to either an original online, interactive smoking cessation program or to a modified program. Both programs consisted of tailored, personalized counseling letters based on participants' characteristics, followed by monthly email reminders. The original program was based on psychological and addiction theory, and on preliminary research conducted in the same population. The modified program was shorter and contained more information on nicotine replacement therapy and nicotine dependence, and less information on health risks and coping strategies. In both programs, 1 month and 2 months after entering the study, participants were invited by email to answer the same tailoring questionnaire again in order to receive a second counseling letter. Participants in both programs obtained, on average, 1.2 feedback counseling letters over 2.5 months, and 84% received only 1 feedback letter. The outcome was self-reported smoking abstinence (no puff of tobacco in the previous 7 days), assessed 2.5 months after entry in the program. We report results from intention-to-treat (ITT) analyses, where all non-respondents at follow-up were counted as smokers.\n The baseline questionnaire was answered by a total of 11969 current (74%) and former (26%) smokers, and the follow-up survey by 4237 people (35%). In an ITT analysis, abstinence rates in baseline current smokers were respectively 10.9% and 8.9% (odds ratio [OR]=1.24, 95% confidence interval [CI]1.08-1.43, P=.003) in the original and modified programs, and 25.2% and 15.7% (OR=1.81, CI 1.51-2.16, P<.001) in baseline former smokers. While we found statistically significant differences in quit rates in smokers in the contemplation stage favoring the original program (OR=1.54, CI 1.18-2.02, P=.002), no between-group differences in quit rates were observed in smokers in the precontemplation (OR=1.07, CI 0.36-3.14, P=.91) and preparation (OR=1.15, CI 0.97-1.37, P=.10) stages of change.\n In smokers in the contemplation stage of change and in former smokers, the original program produced higher smoking abstinence rates than the modified program.", "There are 1.1 billion smokers worldwide. Traditional smoking cessation methods, such as nicotine replacement therapy and smoking cessation groups, yield between 14% and 27% abstinence rates at 6 months. Evidence-based Internet interventions with comparable abstinence rates could be a powerful global tool to reduce tobacco-related morbidity and mortality.\n We report a randomized control trial in which 500 Spanish-speaking and 500 English-speaking adult Internet users, smoking at least 5 cigarettes/day and intending to quit in the next month, were recruited online from 68 countries. Consenting participants who completed baseline measures, logged cigarettes smoked on 3 days within a week, and set a quit date were randomized to four conditions. Each condition added new elements: Condition 1 was the \"Guía Para Dejar de Fumar,\" a static National Cancer Institute evidence-based stop smoking guide; Condition 2 consisted of Condition 1 plus E-mail reminders to return to the site; Condition 3 consisted of Condition 2 plus mood management lessons; and Condition 4 consisted of Condition 3 plus a \"virtual group\" (an asynchronous bulletin board). Main outcome measures were 7-day point prevalence abstinence at 1, 3, 6, and 12 months after initial quit date.\n There were no significant differences among the four conditions. The overall 12-month 7-day abstinence rates were 20.2% for Spanish speakers and 21.0% for English speakers when those with missing data were assumed to be smoking.\n Internet smoking cessation interventions with such abstinence rates provided globally in additional languages could contribute substantially to tobacco control efforts.", "Smoking cessation remains a significant public health problem. Innovative interventions that use the Internet have begun to emerge that offer great promise in reaching large numbers of participants and encouraging widespread behavior change. To date, the relatively few controlled trials of Web-based smoking cessation programs have been limited by short follow-up intervals.\n We describe the 6-month follow-up results of a randomized controlled trial in which participants recruited online were randomly assigned to either a Web-based smoking cessation program (Quit Smoking Network; QSN) or a Web-based exercise enhancement program (Active Lives) adapted somewhat to encourage smoking cessation.\n The study was a two-arm randomized controlled trial that compared two Web-based smoking cessation programs: (1) the QSN intervention condition presented cognitive-behavioral strategies, and (2) the Active Lives control condition provided participants with guidance in developing a physical activity program to assist them with quitting. The QSN condition provided smoking cessation information and behavior change strategies while the Active Lives condition provided participants with physical activity recommendations and goal setting. The QSN condition was designed to be more engaging (eg, it included multimedia components) and to present much greater content than is typically found in smoking cessation programs.\n Contrary to our hypotheses, no between-condition differences in smoking abstinence were found at 3- and 6-month follow-up assessments. While participants in the QSN intervention condition spent more time than controls visiting the online program, the median number of 1.0 visit in each condition and the substantial attrition (60.8% at the 6-month follow-up) indicate that participants were not as engaged as we had expected.\n Contrary to our hypothesis, our test of two Web-based smoking cessation conditions, an intervention and an attention placebo control, failed to show differences at 3- and 6-month assessments. We explored possible reasons for this finding, including limited engagement of participants and simplifying program content and architecture. Future research needs to address methods to improve participant engagement in online smoking cessation programs. Possible approaches in this regard can include new informed consent procedures that better explain the roles and responsibilities of being a research participant, new program designs that add more vitality (changing content from visit to visit), and new types of reminders pushed out to participants to encourage return visits. Simplifying program content through a combination of enhanced tailoring and information architecture also merits further research attention.", "To date, few Internet-delivered smoking cessation interventions have been tested. This study tested the efficacy, understandability, credibility and personal relevance of an e-mail-delivered computer-tailored smoking cessation intervention. It included tailored action plan feedback, as recent studies have demonstrated the importance of planning in facilitating quitting smoking. Participants (Dutch adults) were randomly assigned to the intervention (computer-tailored e-mail; N = 224) or the control group (generic, non-tailored e-mail; N = 234). The results 6 months after baseline (N = 195) showed that significantly more participants in the intervention group reported not having smoked in the last 24 hours (21.5%) and 7 days (20.4%) in contrast with participants in the control group (9.8 and 7.8%, respectively). Intention-to-treat analyses revealed similar results, though overall lower quitting percentages. Furthermore, participants in the intervention group appreciated the computer-tailored e-mail significantly more in terms of understandability, credibility and personal relevance. Hence, the computer-tailored intervention is effective for the Dutch smoking population motivated to quit smoking. Further research is needed into the efficacy of the intervention for smokers who are not motivated to quit smoking and into the benefits of (multiple) e-mail-delivered tailored letters with tailored action plan feedback over and above tailoring without action plan feedback.", "Randomized controlled trials of smoking interventions have not been well-documented for lung cancer screening populations. In this study, we randomly assigned 171 current smokers who were undergoing low-dose fast spiral chest CT (SCTS) for lung cancer screening to receive either standard written self-help materials or a written list of Internet resources for smoking cessation. At the 1-year follow-up, more of the subjects receiving Internet-based resources reported making a stop attempt (68% versus 48%, P=0.011). However, there were no statistically significant differences in 7-day point prevalence quit rates (5% versus 10%) or advancement in motivational readiness to stop smoking (27% versus 30%), respectively, between the groups. Clearly, more investigation is warranted into how to tailor smoking interventions for cancer screening participants.", "Internet interventions for smoking cessation are ubiquitous. Yet, to date, there are few randomized clinical trials that gauge their efficacy. This study is a randomized clinical trial (N= 284, n= 140 in the treatment group, n= 144 in the control group) of an Internet smoking cessation intervention. Smokers were randomly assigned to receive either bupropion plus counseling alone, or bupropion and counseling in addition to 12 weeks of access to the Comprehensive Health Enhancement Support System for Smoking Cessation and Relapse Prevention (CHESS SCRP; a Web site which provided information on smoking cessation as well as support). We found that access to CHESS SCRP was not significantly related to abstinence at the end of the treatment period (OR= 1.13, 95% CI 0.66-2.62) or at 6 months postquit (OR= 1.48, 95% CI 0.66-2.62). However, the number of times participants used CHESS SCRP per week was related to abstinence at both end of treatment (OR= 1.79, 95% CI 1.25-2.56) and at the 6-month follow-up (OR= 1.59, 95% CI 1.06-2.38). Participants with access to CHESS SCRP logged in an average of 33.64 times (SD=30.76) over the 90-day period of access. Rates of CHESS SCRP use did not differ by ethnicity, level of education or gender (all p>.05). In sum, results suggest that participants used CHESS SCRP frequently, CHESS SCRP use was related to success, but the effects in general did not yield intergroup effects.", "To assess the long-term efficacy of a fully automated digital multi-media smoking cessation intervention.\n Two-arm randomized control trial (RCT). Setting World Wide Web (WWW) study based in Norway.\n Subjects (n = 396) were recruited via internet advertisements and assigned randomly to conditions. Inclusion criteria were willingness to quit smoking and being aged 18 years or older.\n The treatment group received the internet- and cell-phone-based Happy Ending intervention. The intervention programme lasted 54 weeks and consisted of more than 400 contacts by e-mail, web-pages, interactive voice response (IVR) and short message service (SMS) technology. The control group received a self-help booklet. Additionally, both groups were offered free nicotine replacement therapy (NRT).\n Abstinence was defined as 'not even a puff of smoke, for the last 7 days', and assessed by means of internet surveys or telephone interviews. The main outcome was repeated point abstinence at 1, 3, 6 and 12 months following cessation.\n Participants in the treatment group reported clinically and statistically significantly higher repeated point abstinence rates than control participants [22.3% versus 13.1%; odds ratio (OR) = 1.91, 95% confidence interval (CI): 1.12-3.26, P = 0.02; intent-to-treat). Improved adherence to NRT and a higher level of post-cessation self-efficacy were observed in the treatment group compared with the control group.\n As the first RCT documenting the long-term treatment effects of such an intervention, this study adds to the promise of digital media in supporting behaviour change.", "Happy Ending (HE) is an intense 1-year smoking cessation program delivered via the Internet and cell phone. HE consists of more than 400 contacts by email, Web pages, interactive voice response, and short message service technology. HE includes a craving helpline and a relapse prevention system, providing just-in-time therapy. All the components of the program are fully automated.\n The objectives were to describe the rationale for the design of HE, to assess the 12-month efficacy of HE in a sample of smokers willing to attempt to quit without the use of nicotine replacement therapy, and to explore the potential effect of HE on coping planning and self-efficacy (prior to quitting) and whether coping planning and self-efficacy mediate treatment effect.\n A two-arm randomized controlled trial was used. Subjects were recruited via Internet advertisements and randomly assigned to condition. Inclusion criteria were willingness to quit on a prescribed day without using nicotine replacement and being aged 18 years or older. The intervention group received HE, and the control group received a 44-page self-help booklet. Abstinence was defined as \"not even a puff of smoke, for the last seven days\" and was assessed by means of Internet surveys or telephone interviews 1, 3, 6, and 12 months postcessation. The main outcome was repeated point abstinence (ie, abstinence at all four time points). Coping planning and self-efficacy were measured at baseline and at the end of the preparation phase (ie, after 2 weeks of treatment, but prior to cessation day).\n A total of 290 participants received either the HE intervention (n=144) or the control booklet (n=146). Using intent-to-treat analysis, participants in the intervention group reported clinically and statistically significantly higher repeated point abstinence rates than control participants (20% versus 7%, odds ratio [OR] = 3.43, 95% CI = 1.60-7.34, P = .002). Although no differences were observed at baseline, by the end of the preparation phase, significantly higher levels of coping planning (t(261) = 3.07, P = .002) and precessation self-efficacy (t(261) = 2.63, P = .01) were observed in the intervention group compared with the control group. However, neither coping planning nor self-efficacy mediated long-term treatment effect. For point abstinence 1 month after quitting, however, coping planning and self-efficacy showed a partial mediation of the treatment effect.\n This 12-month trial documents a long-term treatment effect of a fully automated smoking cessation intervention without the use of nicotine replacement therapy. The study adds to the promise of using digital media in supporting behavior change." ]

[ "19487623", "15602505", "11466160", "8369641", "8911223", "2745390", "16119478" ]

[ "Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism.", "A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism.", "Effect of fluoxetine on regional cerebral metabolism in autistic spectrum disorders: a pilot study.", "Clinical and neurochemical effects of fenfluramine in children with autism.", "A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder.", "Urinary dopamine metabolites as indicators of the responsiveness to fenfluramine treatment in children with autistic behavior.", "Clinical efficacy of fluvoxamine and functional polymorphism in a serotonin transporter gene on childhood autism." ]

[ "Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders.\n To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders.\n National Institutes of Health-sponsored randomized controlled trial.\n Six academic centers, including Mount Sinai School of Medicine, North Shore-Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School.\n One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders.\n Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d).\n Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form.\n There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P > .99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], -2.0 [3.4] points for the citalopram-treated group and -1.9 [2.5] points for the placebo group; P = .81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus.\n Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645.", "Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system. While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism, as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism. This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders (ASDs). In total, 45 child or adolescent patients with ASD were randomized into two acute 8-week phases in a double-blind placebo-controlled crossover study of liquid fluoxetine. Study design included two randomized 8-week fluoxetine and placebo phases separated by a 4-week washout phase. Outcome measures included measures of repetitive behaviors and global improvement. Low-dose liquid fluoxetine (mean final dose: 9.9+/-4.35 mg/day) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale. The effect size was in the moderate to large range, and the doses used were low. Liquid fluoxetine was only slightly, and not significantly, superior to placebo on CGI autism score partially due to a phase order effect. However, fluoxetine was marginally superior to placebo on a composite measure of global effectiveness. Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects. Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism. Limitations include small sample size and the crossover design of the study. Further replication and long-term maintenance trials are needed.", "The regional metabolic effects of fluoxetine were examined in patients with autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1), entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients received (18)F-deoxyglucose positron emission tomography with co-registered magnetic resonance imaging at baseline and at the end of the period of fluoxetine administration. After treatment, the patients showed significant improvement on the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients with higher metabolic rates in the medial frontal region and anterior cingulate when unmedicated were more likely to respond favourably to fluoxetine. These results are consistent with those in depression indicating that higher cingulate gyrus metabolic rates at baseline predict SRI response.", "Fifteen children with autism were treated with 60 mg d,l-fenfluramine (FEN) or placebo in a double-blind A-B-A protocol followed immediately by double-blind placebo-controlled crossover administration of FEN (total duration 62 weeks). Both biochemical and clinical outcomes were examined. Biochemically, FEN led to an increase in dihydroxyphenylacetic acid (DOPAC) and decreases in whole-blood serotonin (5-HT), plasma norepinephrine (NE), and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG). The decrease in whole-blood 5-HT was seen only during treatment with FEN. However, NE levels did not return to baseline as long as 8 weeks after the first FEN treatment period. Increases in DOPAC were greater during the second FEN treatment period than the first. Persistent changes in catecholamine regulation may be related to previously reported long-term effects on central nervous system 5-HT after FEN. Clinically, FEN led to a modest decrease in parent, but not teacher, ratings of hyperactivity and to a small reduction in sensorimotor abnormalities. Abnormal social and affectual responses also decreased, but this was not directly related to FEN treatment. Effects on cognition were equivocal. Hyperserotonemic subjects did not differ from normoserotonemic subjects in clinical response. Overall, no significant advantage for the use of FEN could be established.", "Autistic disorder is characterized by a fundamental disturbance in social interaction, impairments in communication, and a markedly restricted repertoire of activities and interests. Abnormalities in the serotonin neurotransmitter system have been identified in some persons with autism. No consistently effective and safe drugs have been developed for treating the symptoms of autism.\n Thirty adults with autistic disorder completed a 12-week double-blind, placebo-controlled trial of the potent and selective serotonin uptake inhibitor fluvoxamine maleate. Behavioral ratings were obtained at baseline and after 4, 8, and 12 weeks of treatment.\n Eight (53%) of 15 patients in the fluvoxamine-treated group were categorized as responders compared with none of 15 in the placebo group (P = .001). Fluvoxamine was superior to placebo in reducing repetitive thoughts and behavior (P < .001), maladaptive behavior (P < .001), and aggression (P < .03), and in improving some aspects of social relatedness (P < .04), especially language usage (P < .008). Treatment response was not correlated with age level of autistic behavior, or full-scale IQ. Other than mild sedation and nausea in a few patients, fluvoxamine was well tolerated. No dyskinesias, adverse cardiovascular events, or seizures occurred.\n Fluvoxamine is more effective than placebo in the short-term treatment of the symptoms of autistic disorder in adults. Controlled studies of fluvoxamine and other potent and selective serotonin uptake inhibitors seem warranted in children and adolescents with autism.", "Modifications in serotonin and dopamine metabolism were evaluated in 13 children with autistic behavior and related to their responsiveness to fenfluramine treatment. A double-blind medication-placebo crossover design was used. Each patient received 1.5 mg/kg fenfluramine daily for 3 months followed and preceded by placebo for 1 month. Clinical improvement was observed in 6 children (responders). It included reduction of behavioral symptoms such as motor activity, anxiety, mood disturbances, and distractibility. Modifications of serotonin (5-HT), dopamine (DA), and DA metabolites [homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC)] were assessed at urinary levels. Responders and nonresponders showed a significant decrease of urinary 5-HT levels on fenfluramine. The main differences between the two groups of subjects were found with HVA, the major metabolite of DA. Fenfluramine significantly increased HVA levels in responders whereas no significant modification was found in nonresponders. Moreover the initial level of HVA (lower in responders) significantly differentiated the two groups. These results suggest that the clinical response to fenfluramine could be related to the dopaminergic action of this drug and that urinary DA metabolite levels could be considered as indicators of the responsiveness to fenfluramine treatment in children with autistic behavior.", "We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment. 5-HTTLPR (long (l) or short(s)), was analyzed by the PCR method. Ten out of 18 patients responded to fluvoxamine treatment; allele type analysis revealed that clinical global effectiveness was noted significantly more in the l allele than in the s allele. However, with respect to language use, a significant effectiveness was noted in the s allele. 5-HTTLPR may influence the individual responses to fluvoxamine administration." ]

[ "15084618", "15750359", "10703904", "11505416" ]

[ "Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer.", "A pilot, randomized, double-blinded, placebo-controlled trial of individualized homeopathy for symptoms of estrogen withdrawal in breast-cancer survivors.", "Efficacy of homeopathic treatment of skin reactions during radiotherapy for breast cancer: a randomised, double-blind clinical trial.", "A randomized, controlled clinical trial of the homeopathic medication TRAUMEEL S in the treatment of chemotherapy-induced stomatitis in children undergoing stem cell transplantation." ]

[ "The effectiveness of nonsteroid topical agents for the prevention of acute dermatitis during adjuvant radiotherapy for breast carcinoma has not been demonstrated. The goal of this study was to compare the effectiveness of calendula (Pommade au Calendula par Digestion; Boiron Ltd, Levallois-Perret, France) with that of trolamine (Biafine; Genmedix Ltd, France), which is considered in many institutions to be the reference topical agent.\n Between July 1999 and June 2001, 254 patients who had been operated on for breast cancer and who were to receive postoperative radiation therapy were randomly allocated to application of either trolamine (128 patients) or calendula (126 patients) on the irradiated fields after each session. The primary end point was the occurrence of acute dermatitis of grade 2 or higher. Prognostic factors, including treatment modalities and patient characteristics, were also investigated. Secondary end points were the occurrence of pain, the quantity of topical agent used, and patient satisfaction.\n The occurrence of acute dermatitis of grade 2 or higher was significantly lower (41% v 63%; P <.001) with the use of calendula than with trolamine. Moreover, patients receiving calendula had less frequent interruption of radiotherapy and significantly reduced radiation-induced pain. Calendula was considered to be more difficult to apply, but self-assessed satisfaction was greater. Body mass index and adjuvant chemotherapy before radiotherapy after lumpectomy were significant prognostic factors for acute dermatitis.\n Calendula is highly effective for the prevention of acute dermatitis of grade 2 or higher and should be proposed for patients undergoing postoperative irradiation for breast cancer.", "To pilot an investigation of individualized homeopathy for symptoms of estrogen withdrawal in breast cancer survivors.\n Randomized, double-blinded, placebo-controlled trial.\n Outpatient department of a National Health Service (NHS) homeopathic hospital.\n Fifty-seven (57) women met inclusion criteria and 53 were randomized to the study.\n After 2 weeks of baseline assessment, all participants received a consultation plus either oral homeopathic medicine or placebo, assessed every 4 weeks for 16 weeks.\n The primary outcome measures were the activity score and profile score of the Measure Yourself Medical Outcome Profile (MYMOP).\n Eighty-five percent (85%) (45/53) of women completed the study. There was no evidence of a difference seen between groups for either activity (adjusted difference =-0.4, 95% confidence interval CI -1.0 to 0.2, p = 0.17) or profile scores (adjusted difference = -0.4, 95% CI -0.9 to 0.1, p = 0.13) using this trial design, although post hoc power calculations suggests that 65-175 would be needed per group to detect differences of this magnitude with sufficient precision. Clinically relevant improvements in symptoms and mood disturbance were seen for both groups over the study period.\n Improvements were seen for symptom scores over the study period. However, presuming these improvements were caused by the individualized homeopathic approach, the study failed to show clearly that the specific effect of the remedy added further to the nonspecific effects of the consultation. Future trial design must ensure adequate power to account for the nonspecific impact of such complex individualized interventions while pragmatic designs may more readily answer questions of clinical and cost effectiveness.", "The aim of this study was to assess the effects of Belladonna 7cH and X-ray 15cH associated in the treatment of acute radiodermatitis. A randomized double-blind placebo-controlled clinical trial involving 66 patients who had been operated on for breast cancer and were undergoing radiotherapy was conducted. The following parameters were assessed over ten weeks: breast skin colour, warmth, swelling and pigmentation. The efficacy of the treatment was assessed by the comparison of these parameters taken individually and by calculating an Index of Total Severity (sum of the scores of the four parameters) during radiotherapy, and during recovery, 15 and 30 d after the end of the radiotherapy. The differences of the scores of the Index of Total Severity during Radiotherapy were not statistically significant, but showed a trend towards a better activity of the homoeopathic medicine compared to placebo. Analysis of the data on Total Severity during recovery, showed a statistically significant benefit of the active medicines over placebo. The homeopathic medicines had particular effectiveness on the heat of the skin. The limited number of patients observed and the posology employed could have interfered with the significance of the results. Chemotherapy and hormonotherapy do not seem to affect the results.", "Stomatitis is a common consequence of chemotherapy and a condition for which there is little effective treatment. Although the management of patients with other chemotherapy-related toxicities has improved in recent years, the incidence of stomatitis is increasing because of more intensive treatment and is often a dose limiting factor in chemotherapy. The authors assessed the efficacy of a homeopathic remedy, TRAUMEEL S(R), in the management of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation.\n A randomized, placebo-controlled, double-blind clinical trial was conducted in 32 patients ages 3-25 years who had undergone allogeneic (16 patients) or autologous (16 patients) stem cell transplantation. Of the 30 evaluable patients, 15 were assigned placebo, and 15 were assigned TRAUMEEL S both as a mouth rinse, administered five times daily from 2 days after transplantation for a minimum of 14 days, or until at least 2 days after all signs of stomatitis were absent. Stomatitis scores were evaluated according to the World Health Organization grading system for mucositis.\n A total of five patients (33%) in the TRAUMEEL S treatment group did not develop stomatitis compared with only one patient (7%) in the placebo group. Stomatitis worsened in only 7 patients (47%) in the TRAUMEEL S treatment group compared with 14 patients (93%) in the placebo group. The mean area under the curve stomatitis scores were 10.4 in the TRAUMEEL S treatment group and 24.3 in the placebo group. This difference was statistically significant (P < 0.01).\n This study indicates that TRAUMEEL S may reduce significantly the severity and duration of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation.\n Copyright 2001 American Cancer Society." ]

[ "12074203", "3307858", "9048790", "8021700", "10443094", "2367299", "2043179", "1457907", "59150", "3555580", "15808032", "1520054", "6346830", "8323792", "2051002", "2669346" ]

[ "Effectiveness of quinine in treating muscle cramps: a double-blind, placebo-controlled, parallel-group, multicentre trial.", "Randomised double-blind trial of quinine sulphate for nocturnal leg cramp.", "Randomised controlled trial of hydroquinine in muscle cramps.", "Efficacy of hydroquinine in preventing frequent ordinary muscle cramp outlasts actual administration.", "The relationship between myofascial trigger points of gastrocnemius muscle and nocturnal calf cramps.", "Nocturnal cramp: quinine versus folklore.", "[Treatment of nocturnal leg cramps. A multicenter, double blind, placebo controlled comparison between the combination of quinine and theophylline ethylene diamine with quinine].", "Dialysis leg cramps. Efficacy of quinine versus vitamin E.", "Prevention of muscle cramps in haemodialysis patients by quinine sulphate.", "A quinine a day keeps the leg cramps away?", "N-of-1 trials of quinine efficacy in skeletal muscle cramps of the leg.", "Treatment of nocturnal leg cramps. A crossover trial of quinine vs vitamin E.", "A double-blind comparison of quinine sulphate and placebo in muscle cramps.", "Effectiveness of quinine for night cramps.", "A randomized controlled trial of quinidine in the treatment of cirrhotic patients with muscle cramps.", "Placebo-controlled trial of quinine therapy for nocturnal leg cramps." ]

[ "To determine the efficacy and safety of quinine in treating nocturnal muscle cramps we performed a double-blind, placebo-controlled, parallel-group, multicentre trial in 17 general practice centres in Germany. Ninety-eight patients aged 18-70 years with more than six muscle cramps in two weeks were enrolled. A two-week run-in period without treatment was followed by two weeks of treatment with 400 mg quinine or placebo per day and a wash-out period of two weeks without treatment. The primary outcome measure was the reduction in the number of muscle cramps between the run-in and treatment periods. The intensity of cramps, number of nights with cramps, sleep disturbance and intensity of pain were recorded as secondary outcome measures. At baseline the median number of cramps was 12 in two weeks in both groups. The median reduction between the run-in and therapy phases was eight (95% CI 7-10) versus six (95% CI 3-7) muscle cramps during quinine and placebo treatment; 36 (80%) participants in the quinine group and 26 (53%) in the placebo group had a reduction of at least 50% in the number of muscle cramps. Frequency, intensity and pain at night showed a statistically significant difference in favour of quinine. The improvement was more evident according to physician assessment than patient assessment; this is corroborated by the high placebo response rate. No significant differences were found between the two groups with respect to side-effects. Short term treatment with 400 mg quinine per day can effectively prevent nocturnal leg cramps in adults without relevant side-effects.", "nan", "Although quinine and hydroquinine are commonly prescribed for muscle cramps, controlled clinical trials of these drugs have reported mixed findings about efficacy. We investigated hydroquinine therapy in otherwise healthy adults who had frequent, ordinary muscle cramps.\n This randomised, double-blind, placebo-controlled, parallel-group trial consisted of three consecutive 2-week periods: qualification, treatment, and washout, 68 women and 44 men who had at least three muscle cramps per week were enrolled. During the treatment period, participants were randomly assigned 300 mg daily dose of hydroquinine hydrobromide dihydrate (54 participants) or placebo (58). The frequency, severity (1-10), duration, and location of muscle cramps, as well as any side-effects, were recorded by participant in daily diaries. The primary outcome measures were the number of muscle cramps and the number of days during which the participants had muscle cramps (cramp-days).\n We excluded five participants from both groups from the analysis. Thus, data from 49 hydroquinine-group participants and 53 placebo-group participants were analysed. In both groups the total number of muscle cramps and the number of cramp-days decreased during the treatment period compared with the qualification period. However, these improvements were greater in the hydroquinine group than in the placebo group. The hydroquinine-group participants reported a median of 8 (95% CI 7-12) fewer cramps and median of 3 (1-4) fewer cramp-days, whereas those on placebo reported only 3 (0-5) fewer cramps and 1 (0-5) fewer cramp-days. 32 (65%) of participants in the hydroquinine group had a 50% or greater reduction in the number of muscle cramps. After the onset of cramps, hydroquinine did not reduce the severity or duration of cramps. We also found a sustained effect after treatment had stopped. Hydroquinine was well tolerated, and resulted in only mild side-effects.\n In our study, 300 mg hydroquinine was safe to take in the short-term and significantly more effective than placebo in the prevention of frequent, ordinary muscle cramps. This therapeutic effect outlasted the duration of treatment.", "In order to compare the efficacy of a daily dose of 300 mg hydroquinine hydrobromide and placebo in preventing frequent ordinary muscle cramp, we designed a randomized, double-blind, placebo-controlled study of three consecutive 2-week periods viz. a qualification period, a medication period and a wash-out period. Twenty healthy adult volunteers experiencing at least 3 muscle cramps a week (6 men, 14 women aged 38-78 yrs) were enrolled into this study, and 19 of them completed it. Hydroquinine hydrobromide (300 mg/day) was administered to group 1 (10 women) and placebo to group 2 (4 women, 6 men). The frequency, severity, duration and location of muscle cramps as well as short-term adverse drug effects were recorded in daily diaries. Compared with placebo the decrease in the mean number of muscle cramps (16.1 or 58%) in the active drug treatment group during the medication period was highly significant (Wilcoxon test p = 0.004). During the wash-out period this decrease partly persisted (8.9 or 33%). In this study a daily dose of 300 mg hydroquinine hydrobromide was effective in preventing frequent ordinary muscle cramp in healthy female volunteers. The effects of hydroquinine outlasted its administration. The drug was well tolerated.", "To support that myofascial pain syndrome (MPS) of gastrocnemius muscle is one cause of nocturnal calf cramps, quantitative assessment of the efficacy of trigger point (TrP) injection compared with oral quinine in the treatment of nocturnal calf cramps (NCC) associated with MPS of gastrocnemius muscle was designed. Twenty four subjects with NCC and gastrocnemius TrPs were randomly divided into two groups of twelve for each treatment. Patients in group 1 were treated with xylocaine injection at the gastrocnemius TrP, and 300 mg of quinine sulfate p.o. was prescribed for patients of group 2. The treatment period was four weeks with a follow-up 4 weeks later. Cramps were assessed quantitatively (in terms of frequency, duration, pain intensity, cramp index, and pain threshold of the gastrocnemius TrPs) before treatment, after treatment and at the end of the follow-up respectively. The outcome of treatment in both groups showed a statistically significant reduction in all quantitative aspects of cramps (95% confidence interval). Also the pain threshold of the gastrocnemius TrP was significantly increased in group 1 only when comparing the pre-treatment and at the end of follow-up. In comparing the two groups we found no statistical difference during the period of treatment. The benefit of both strategies lasted up to four weeks following cessation of the treatment but the outcome of all measures (except pain threshold) were found to be significantly better in the group treated with TrP injection. The results of this study support that gastrocnemius trigger point is one cause of NCC and show that the TrP injection strategy for NCC associated with myofascial pain is not only as effective as oral quinine during the treatment period but also better in the prolonged effect at follow-up.", "nan", "164 patients (m = 45, w = 119; age 55.7 +/- 14.7 years) took part in a multicentric controlled parallel-double blind study in which efficacy and tolerability of the combination quinine sulfate (CAS 6119-70-6) plus theophylline ethylene diamine (CTED, CAS 317-34-0) (Limptar) in the treatment of the recurrent nocturnal leg cramps were investigated. Only patients who suffered before the begin of the study in at least three nights per week from leg cramps were included. The duration of the study was three weeks. In the first week all patients were treated in a single blind design with placebo. The subsequent 2 weeks were carried out double-blind. The global efficacy judged by the physicians and investigated for the 126 patients who took the compounds at least four days within the random phase was remarkably better for the combination than for quinine or placebo (very good and good in 87.1 vs. 63.7 vs. 39.5% of the cases; p less than 0.001; x-test). In 117 patients an analysis of the time course of the efficacy could be done from the notes in the diary (minimum duration of treatment 11 d). Already within the first week there was a highly significant decrease of nights with leg cramps within the CTED group (n = 34) from 4.68 (95% confidential interval 2.26-7.0) to 2.25 (0-6.78) in comparison to placebo (n = 40; from 4.32 [1.9-7.0] to 3.69 [1.22-6.91]) and quinine (n = 43; from 4.78 [2.22-7.0] to 3.27 [0-7.0]; F-test; p = 0.0001 resp. 0.0012).(ABSTRACT TRUNCATED AT 250 WORDS)", "A controlled randomized double-blind study was done to determine the frequency and severity of leg cramps in 40 patients on dialysis with a history of leg cramps. All patients entered a 2 month placebo washout and were randomized into a 2 month double-dummy phase of quinine 325 mg at bedtime versus vitamin E 400 IU at bedtime. Of the 29 patients completing the study, 16 received quinine and 13 vitamin E. During placebo washout, the vitamin E group had a mean of 10.4 leg cramps per month, and the quinine group had a mean of 10.9. The vitamin E and quinine groups had a 1 month reduction in leg cramps to 3.3 and 3.6, respectively (p < 0.0005 for both groups combined); this was sustained at 2 months. A severity of pain index showed a statistically significant decrease for both groups. The 95% confidence interval for the difference between the number of leg cramps after vitamin E versus quinine treatment (95% confidence interval, -3.8, +3.2) suggests similar efficacy. Quinine and vitamin E were effective treatments for leg cramps in these patients. Considering the potential toxicity of quinine, vitamin E is recommended as the initial treatment of choice for patients on dialysis with leg cramps.", "Nine patients on maintenance haemodialysis with frequent muscle cramps were given 320 mg quinine sulphate or placebo (in an identical gelatin capsule) at the beginning of each dialysis for a period of 12 weeks. The frequency of cramps was significantly reduced during dialysis in patients receiving quinine sulphate. None of the haematological, auditory, or visual disturbances ascribed to quinine sulphate were noted.", "A double-blind, placebo-controlled, cross-over trial of quinine in leg cramps occurring at rest was conducted in 22 elderly cramp sufferers. Despite demonstration of impaired quinine elimination in the elderly, prescription of the traditional dose of 300 mg quinine bisulphate at night failed to produce a significant (P = 0.1) reduction in the number or severity of cramps. There was a significant relationship between serum quinine concentration and attenuation of cramps. However, the simple expedient of increasing the nightly dose of quinine may carry the concomitant risk of cinchonism.", "Skeletal muscle cramps affect over a third of the ambulatory elderly population. Quinine is the established treatment, but there are safety concerns, and evidence for efficacy is conflicting. A recent meta-analysis established a small advantage for quinine, but identified the need for additional studies. N-of-1 trials compare two treatments, in a randomised, double-blind, multiple crossover study on a patient-by-patient basis. They have been used to compare treatments in osteoarthritis and may be suitable for determining the individual efficacy of quinine.\n To establish efficacy and safety of quinine sulphate use for the treatment of leg-muscle cramp.\n Double-blind, randomised series of n-of-1 controlled trials of quinine versus placebo for muscle cramps.\n New Zealand general practices.\n The participants were 13 general practice patients (six males; seven females; median age = 75 years) already prescribed quinine. Following a 2-week washout, each patient received three 4-week treatment blocks of quinine sulphate and matched placebo capsules with an individual, randomised crossover design. The main outcome measures were: patient diaries of cramp occurrence, duration and severity; capsule counts; and blood quinine levels in the final treatment block.\n Ten patients completed the trial. Three patients were identified for whom quinine was clearly beneficial (P <0.05), six showed non-significant benefit and one showed no benefit. All patients elected to continue quinine post-study.\n Series of n -of-1 studies differentiated patients whom quinine had statistically significant effects; those with trend towards effectiveness; those for whom quinine was probably not effective. Ideally n-of-1 trial should be performed when a patient is commenced on quinine. More cycles in n-of-1 studies of quinine may address issues of statistical power.", "This study compared the efficacy and safety of quinine sulfate, vitamin E, and placebo in the treatment of nocturnal leg cramps.\n A random-order, double-blind, placebo-controlled crossover trial was performed.\n The study was conducted at the Veterans Affairs Medical Center, White River Junction, Vt.\n Twenty-seven male veterans, aged 38 to 73 years, who experienced at least six leg cramps per month were recruited through the general medicine walk-in clinic or were referred from other clinics. Fifty-five subjects were contacted, 30 were enrolled consecutively, and 27 completed the study.\n Subjects received, in random order, quinine sulfate (200 mg at supper and 300 mg at bedtime), vitamin E (800 U at bedtime), or placebo for 4-week periods. These periods were separated by 4-week washout intervals.\n Patients reported cramp frequency, severity, and sleep disturbance caused by cramps.\n Compared with treatment with placebo, quinine reduced the frequency of cramps and sleep disturbance, but not the average cramp severity. Thirteen of 27 patients had at least a 50% reduction in the number of cramps while receiving quinine; the response was usually seen within 3 days. There was evidence of a mild increase in side effects while subjects received quinine. Vitamin E was not effective in reducing leg cramp frequency, severity, or sleep disturbance.\n Quinine sulfate, but not vitamin E, is superior to placebo in the treatment of nocturnal leg cramps.", "Muscle cramps are painful and common in elderly patients but have largely escaped medical investigation. Quinine sulphate is usually the sole drug prescribed, even though firm evidence for its efficacy is not available. The results of the present double-blind cross-over study show that quinine was significantly superior to placebo in decreasing the number, severity and duration of nocturnal cramps. Since quinine is not a primary drug in any other condition, further studies of drugs with similar pharmacological actions may thus improve our management of this painful complaint.", "nan", "In an attempt to evaluate the effect of quinidine in the treatment of patients with cirrhosis and muscle cramps, 31 cirrhotic patients with muscle cramps were randomly divided into two groups and given orally 400 mg of quinidine sulfate per day or placebo, respectively. Baseline clinical and laboratory data for these two groups were similar. Four weeks after oral administration of quinidine, the number of cramps significantly decreased from 14.4 +/- 1.7 (mean +/- S.E.) to 4.4 +/- 1.1 episodes (p less than 0.0001), but it remained unchanged in the placebo group (from 11.8 +/- 1.0 to 11.5 +/- 1.5 episodes, p greater than 0.05). In addition, 88% of the 16 patients on quinidine and 13% of the 15 patients on a placebo showed a greater than 50% reduction in the number of cramps during a 4-week treatment period (p less than 0.0001). The peak and trough serum levels of quinidine in patients having received quinidine for 2 weeks were 1.3 +/- 0.1 and 0.7 +/- 0.1 mg/l, respectively. There was a significant relationship between serum quinidine concentrations and attenuation of cramps. No significant adverse effect was observed during the study, except for five (31%) patients who developed mild diarrhea after quinidine therapy. Diarrhea subsided spontaneously or was controlled by medications without the interruption of quinidine therapy. It was concluded that quinidine is a safe and effective drug for the treatment of cirrhotic patients with muscle cramps.", "A prospective, double-blind, placebo-controlled crossover study of the use of quinine for nocturnal leg cramps was carried out in 8 elderly volunteer patients. The patients were randomly assigned to receive either placebo or 200 mg of quinine sulfate by mouth at bedtime. After 4 weeks of treatment and after a one-week washout period, the group taking quinine switched to placebo and vice versa for another 4 weeks. The differences in the number, duration, and severity of cramps and the side effects were compared. All of the patients had fewer cramps and decreased severity and duration of attacks while receiving quinine. Mild side effects developed in only 2 patients, and these subsided without treatment or discontinuing the medication. We conclude that quinine was effective in relieving nocturnal leg cramps in a selected group of elderly patients." ]

[ "7711427", "8410923", "1325010", "10916100", "8488862", "11347755", "9867064", "11565518", "11353877", "9269212", "15723969", "8541002", "2507061", "15498085", "14960504", "11325669", "8167383", "14586718", "9538979", "10675071", "12706322", "10851564", "11128360", "16020405", "7548979", "8158885", "1310913", "8239321", "11855793", "11921421", "7485207", "9314638", "8452322", "8062609", "3038254", "8960857", "11289051", "8596594", "11796177", "15516696", "8462386", "7859897", "10361863", "11565517", "11422755", "11565519" ]

[ "Effects of captopril treatment versus placebo on renal function in type 2 diabetic patients with microalbuminuria: a long-term study.", "Placebo-controlled trial of lisinopril in normotensive diabetic patients with incipient nephropathy.", "Treatment of arterial hypertension in diabetic humans: importance of therapeutic selection.", "Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy.", "Diabetic microalbuminuria and cilazapril.", "Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes.", "Effects of perindopril on renal histomorphometry in diabetic subjects with microalbuminuria: a 3-year placebo-controlled biopsy study.", "Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.", "Early ACE-i intervention in microalbuminuric patients with type 1 diabetes: effects on albumin excretion, 24 h ambulatory blood pressure, and renal function.", "Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. The EUCLID Study Group.", "Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus.", "Effect of low-dose ramipril on microalbuminuria in normotensive or mild hypertensive non-insulin-dependent diabetic patients. North-East Italy Microalbuminuria Study Group.", "Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy.", "Long-term renoprotection by perindopril or nifedipine in non-hypertensive patients with Type 2 diabetes and microalbuminuria.", "Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study).", "Long-term comparison between perindopril and nifedipine in normotensive patients with type 1 diabetes and microalbuminuria.", "ACE inhibitor mediated reductions in renal size and microalbuminuria in normotensive, diabetic subjects.", "Effects of the angiotensin II type 1 receptor antagonist candesartan, compared with angiotensin-converting enzyme inhibitors, on the urinary excretion of albumin and type IV collagen in patients with diabetic nephropathy.", "Effects of lisinopril and nifedipine on the progression to overt albuminuria in IDDM patients with incipient nephropathy and normal blood pressure. The Italian Microalbuminuria Study Group in IDDM.", "Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators.", "Effect of 5-year enalapril therapy on progression of microalbuminuria and glomerular structural changes in type 1 diabetic subjects.", "The effects of a low-dose regimen of fosinopril on elevated urinary albumin excretion in normotensive type 1 diabetic patients.", "Low-dose ramipril reduces microalbuminuria in type 1 diabetic patients without hypertension: results of a randomized controlled trial.", "Stabilization and regression of albuminuria in Chinese patients with type 2 diabetes: a one-year randomized study of valsartan versus enalapril.", "Possible effect of angiotensin-converting enzyme inhibition on glomerular charge selectivity.", "Renal protective effects of enalapril in hypertensive NIDDM: role of baseline albuminuria.", "Persistent albuminuria in normotensive non-insulin-dependent (type II) diabetic patients: comparative effects of angiotensin-converting enzyme inhibitors and beta-adrenoceptor blockers.", "Angiotensin-converting enzyme inhibitor treatment for young normotensive diabetic subjects: a two-year trial.", "Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study.", "Effects of angiotensin II receptor antagonist on endothelial vasomotor function and urinary albumin excretion in type 2 diabetic patients with microalbuminuria.", "The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group.", "Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria.", "Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients.", "Effects of long-term enalapril treatment on persistent micro-albuminuria in well-controlled hypertensive and normotensive NIDDM patients.", "Converting enzyme inhibition and kidney function in normotensive diabetic patients with persistent microalbuminuria.", "Appropriate Blood Pressure Control in NIDDM (ABCD) Trial.", "Effect of 3 years of antihypertensive therapy on renal structure in type 1 diabetic patients with albuminuria: the European Study for the Prevention of Renal Disease in Type 1 Diabetes (ESPRIT).", "Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.", "Effect of captopril or imidapril on the progression of diabetic nephropathy in Japanese with type 1 diabetes mellitus: a randomized controlled study (JAPAN-IDDM).", "Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy.", "Renal function changes in microalbuminuric normotensive type II diabetic patients treated with angiotensin-converting enzyme inhibitors.", "Effects of captopril on ambulatory blood pressure, renal and cardiac function in microalbuminuric type 1 diabetic patients.", "Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group.", "Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.", "Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients.", "The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes." ]

[ "We evaluated the renal effect of long-term antihypertensive treatment (12 months) with the angiotensin-converting enzyme inhibitor captopril compared to placebo in 15 type 2 diabetic patients with microalbuminuria. The patients were randomly allocated to captopril (n = 9) or placebo (n = 6). After 1-year therapy no significant decrease in blood pressure was demonstrated with captopril (139 +/- 17/80 +/- 9 versus 138 +/- 13/76 +/- 6 mmHg) or placebo (138 +/- 9/75 +/- 6 versus 135 +/- 14/79 +/- 10 mmHg). Only in a small hypertensive subgroup (n = 4) treated with captopril did we find a significant reduction in blood pressure (154 +/- 2/88 +/- 1 versus 142 +/- 7/78 +/- 5 mmHg, P < 0.05). The urinary albumin excretion rate did not change significantly either in the captopril group (95.6 mg/24 h, 25th percentile 138.4, 75th percentile 25.1; versus 127.8 mg/24 h, 25th percentile 29.3, 75th percentile 222) or in the placebo group (99.2 mg/24 h, 25th percentile 58.5, 75th percentile 125.8; versus 120.9 mg/24 h, 25th percentile 62.1, 75th percentile 179.7). There were also no alterations in renal blood flow or filtration rate. In the hypertensive subgroup treated with captopril a reduction in urinary albumin excretion rate after 3 and 6 months of treatment was observed (captopril 73.4 versus 24 and 41 mg/24 h, P < 0.05), but not after 12 months. Triglyceride and cholesterol levels remained constant before and after treatment while glycosylated hemoglobin decreased significantly after 12 months captopril (7.8 +/- 0.9 versus 6.9 +/- 0.7 mg%, P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)", "To study the effects of an angiotensin converting enzyme inhibitor, lisinopril, on renal function in incipient diabetic nephropathy, a prospective double-blind randomised placebo-controlled single centre study was set up at our outpatient diabetic-renal clinic. There were 27 patients with Type I and Type II diabetes with an albumin excretion rate of between 20 micrograms/min and 200 micrograms/min, respectively and no hypertension. Intervention treatment with placebo or low dose lisinopril was for 48 weeks. The main outcome changes were in urinary albumin excretion rate, urinary prostaglandin excretion, and glomerular filtration rate. Secondary outcome measures included changes in BP and heart rate. Of the 32 patients entered into the study, 27 completed 48 weeks treatment (12 lisinopril, 15 placebo). Mean (+/- SD) urinary albumin excretion rate fell from 57.6 (25.7) micrograms/min (n = 15) at visit 1 to 26.8 (26.7) micrograms/min (n = 12) at visit 7 after 48 weeks treatment in the lisinopril group but not in the placebo group: 119.2 (116.6) micrograms/min (n = 17) vs. 113.7 (77.0) micrograms/min (n = 15). There was a least squares mean treatment difference of -67.6 micrograms/min (95% confidence interval (CI), -115.0 to -20.2, P < 0.01) in favour of lisinopril compared with placebo. After 48 weeks treatment seven lisinopril treated patients were normoalbuminuric and five were microproteinuric; three placebo treated patients were normoalbuminuric, nine were microalbuminuric and three were macroproteinuric. Excretion of prostaglandin-F1 alpha (PGF1 alpha) and thromboxane-B2 (TXB2) fell in the lisinopril treated group.(ABSTRACT TRUNCATED AT 250 WORDS)", "This study was undertaken to test the hypothesis that, given equal arterial pressure reductions, the combination of an angiotensin converting enzyme (ACE) inhibitor and calcium antagonist slows declines in renal function and yields greater reductions in albuminuria over either agent alone. This hypothesis was evaluated in four groups of hypertensive, non-insulin dependent, diabetic subjects with renal insufficiency (N = 30). Renal hemodynamics, albuminuria and metabolic parameters were evaluated for a period of one year. Subjects were all placed on a 90 mEq sodium, 0.8 g/kg protein, 1500 calorie American Diabetes Association diet for the entire length of the study. Subjects were followed for two weeks off antihypertensive medications and were subsequently randomized to either lisinopril, alone (group I), sustained release verapamil, alone (group II), reduced doses of both lisinopril and sustained release verapamil (group III), and hydrochlorothiazide with guanfacine (group IV). At the end of one year group III had the greatest reduction in albuminuria (78 +/- 7%, group III vs. 59% +/- 4, group I: P less than 0.05). In addition, the decline in glomerular filtration rate (GFR) was the lowest in this group (0.28 +/- 0.07, group III vs. 0.69 +/- 0.12, group I; P less than 0.05) although there was no significant difference between groups II and IV. The highest side effect profiles were noted in group IV, the least in group III. The greatest reductions in renal hemodynamics occurred in all groups within the first month; however, striking differences between groups were noted (7.4 +/- 2%, group I vs. 1.4 +/- 2%, group III; P less than 0.05). We conclude that the combination of reduced doses of an ACE inhibitor and calcium antagonist attenuate both albuminuria and the rate of decline in glomerular filtration rate. Furthermore, the combination of these classes of agents appear to yield the lowest side effect profile over either agent alone. Lastly, high doses of ACE inhibition alone may be detrimental to renal function in late stage diabetics with renal insufficiency.", "The objectives of this study were to compare the effects of the angiotensin II receptor blocker, losartan, to those of the angiotensin-converting enzyme inhibitor, enalapril, on albuminuria and renal function in relationship to clinic and ambulatory blood pressure (ABP) in hypertensive type 2 diabetic subjects with early nephropathy. The tolerability of these agents and their effect on the metabolic profile were also evaluated.\n The study was a one-year prospective, double-blind trial with losartan and enalapril administered alone or in combination with hydrochlorothiazide and other antihypertensive agents. ABP and renal and biochemical parameters were measured at baseline and after 12, 28, and 52 weeks of active treatment. Ninety-two hypertensive type 2 diabetics with early nephropathy completed the study.\n Both losartan and enalapril administered alone or in combination with other agents induced significant reductions in sitting clinic (P < 0.05) and ABP (P < 0.002) without a statistical difference between groups. Geometric means for urinary albumin excretion (UAE) decreased significantly (P < 0.001) in patients treated with losartan from 64. 1 to 41.5 microg/min and in those treated with enalapril from 73.9 to 33.5 microg/min after 52 weeks of therapy. A significant relationship (P < 0.05) between changes in systolic and diastolic ABP and the decrease in UAE at 52 weeks was seen in both groups. The decline in glomerular filtration rate (GFR) was stabilized at the end of therapy and was identical in both treatment groups. Treatment with enalapril was associated with a significantly higher incidence of cough (P = 0.006) and a rise in serum uric acid (P = 0.002) compared with losartan.\n Our results indicate that a one-year course of antihypertensive therapy with either losartan or enalapril significantly reduces UAE in hypertensive type 2 diabetic patients with early nephropathy. The reduction in UAE with each treatment is similarly related to decrements in ABP. In addition, the rate of decline in GFR is similar in both treatment groups.", "nan", "To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes.\n Ramipril was administered double blind at two different doses (1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo (n = 18) after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55; women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA).\n Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups.\n Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated.", "We conducted a 3-year randomized placebo-controlled double-blind study to determine the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril (PE) on the progress of renal function and histology in subjects with diabetes and microalbuminuria. Forty non-insulin-dependent (NIDDM) and insulin-dependent (IDDM) diabetic subjects, either normotensive or hypertensive, were randomly assigned to receive PE (n = 20) or placebo (n = 20). A percutaneous renal biopsy was performed initially in all patients and repeated in 29 patients after 3 years. The mean glomerular volume, glomerular basement membrane (GBM) thickness, interstitial fibrosis, sclerosed glomeruli, and volume fraction of capillary lumina were measured histomorphometrically. Before treatment, both groups had similar clinical characteristics, blood pressure, glycosylated hemoglobin (Hb), albumin excretion rate, glomerular filtration rate (GFR), serum creatinine, and renal structural damage. Blood pressure was well controlled in both groups. After 3 years' therapy, there was no significant change in renal function and albuminuria in the PE or placebo groups. The increase in GBM thickness in nine paired biopsies was significantly less in PE-treated subjects (P = .0275). Interstitial fibrosis tended to increase less in the PE group, although this did not reach statistical significance. This study indicates that long-term therapy with PE may decrease or delay the progression of structural glomerular damage in microalbuminuric diabetic subjects.", "Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not available for patients with type 2, the most common form of diabetes. We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy.\n A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years. The primary outcome was the composite of a doubling of the base-line serum creatinine concentration, end-stage renal disease, or death. Secondary end points included a composite of morbidity and mortality from cardiovascular causes, proteinuria, and the rate of progression of renal disease.\n A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02). Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25 percent; P=0.006) and end-stage renal disease (risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blood pressure. The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005). The level of proteinuria declined by 35 percent with losartan (P<0.001 for the comparison with placebo).\n Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated.", "To study the effects of ACE-i in type 1 diabetic patients with early microalbuminuria with regard to: i) UAE, ii) 24 h AMBP, including the effect on diurnal BP variation, and iii) renal haemodynamics.\n 58 patients with urinary albumin excretion (UAE) between 20-70 microg/min were treated for two years with either the ACE inhibitor (ACE-i) lisinopril (20 mg od) or placebo in two randomised placebo controlled double blind studies. In a subgroup of patients (n=22) we performed 24 h ambulatory blood pressure measurements (AMBP) and renal function tests (constant infusion technique).\n i) Changes in UAE over the two years were significantly different (p<0.01) in the two groups with final UAE in the lisinopril group of 19.1 microg/min x/divide 2.5 (geometric mean x/divide tolerance factor) and 44.1 microg/min x/divide 2.8 in the placebo group. In the lisinopril group 20 patients (60.6%) reversed to normoalbuminuria compared to 6 patients (24%) in the placebo group (p<0.02). ii) Clinical BP measurements revealed no differences between groups, but by AMBP significant reductions were detectable in the lisinopril group, primarily in night AMBP (systolic/diastolic: - 6.9 +/- 8.6/- 6.0 +/- 5.3 mmHg, p<0.01) as opposed to increases in the placebo group (3.1 +/- 9.3/1.9 +/- 7.3 mmHg). iii) Changes in UAE and changes in filtration fraction (FF) were positively correlated in the intervention group (r=0.9, p<0.01), i.e. the patients who showed the greatest fall in UAE were the ones with the greatest fall in FF.\n ACE-i treatment in patients with low-grade microalbuminuria reduces 24 h AMBP without attenuating diurnal blood pressure variation, reduces UAE significantly, with changes in UAE being strongly associated with changes in FF. Furthermore, compared to placebo, ACE-i reverses micro- to normoalbuminuria in a significant fraction of patients.", "Renal disease in people with insulin-dependent diabetes (IDDM) continues to pose a major health threat. Inhibitors of angiotensin-converting enzyme (ACE) slow the decline of renal function in advanced renal disease, but their effects at earlier stages are unclear, and the degree of albuminuria at which treatment should start is not known.\n We carried out a randomised, double-blind, placebo-controlled trial of the ACE inhibitor lisinopril in 530 men and women with IDDM aged 20-59 years with normoalbuminuria or microalbuminuria. Patients were recruited from 18 European centres, and were not on medication for hypertension. Resting blood pressure at entry was at least 75 and no more than 90 mm Hg diastolic, and no more than 155 mm Hg systolic. Urinary albumin excretion rate (AER) was centrally assessed by means of two overnight urine collections at baseline, 6, 12, 18, and 24 months.\n There were no difference in baseline characteristics by treatment group; mean AER was 8.0 micrograms/min in both groups; and prevalence of microalbuminuria was 13% and 17% in the placebo and lisinopril groups, respectively. On intention-to-treat analysis at 2 years, AER was 2.2 micrograms/min lower in the lisinopril than in the placebo group, a percentage difference of 18.8% (95% CI 2.0-32.7, p = 0.03), adjusted for baseline AER and centre, absolute difference 2.2 micrograms/min. In people with normoalbuminuria, the treatment difference was 1.0 microgram/min (12.7% [-2.9 to 26.0], p = 0.1). In those with microalbuminuria, however, the treatment difference was 34.2 micrograms/min (49.7% [-14.5 to 77.9], p = 0.1; for interaction, p = 0.04). For patients who completed 24 months on the trial, the final treatment difference in AER was 38.5 micrograms/min in those with microalbuminuria at baseline (p = 0.001), and 0.23 microgram/min in those with normoalbuminuria at baseline (p = 0.6). There was no treatment difference in hypoglycaemic events or in metabolic control as assessed by glycated haemoglobin.\n Lisinopril slows the progression of renal disease in normotensive IDDM patients with little or no albuminuria, though greatest effect was in those with microalbuminuria (AER > or = 20 micrograms/min). Our results show that lisinopril does not increase the risk of hypoglycaemic events in IDDM.", "Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker, candesartan cilexetil, on indices of subcutaneous small resistance artery structure in 15 patients with mild hypertension and NIDDM. Eight patients were treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from the gluteal region at baseline and after 1 year of treatment. Small arteries were dissected and mounted on a micromyograph and the media-to-internal lumen ratio was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was assessed. A similar blood pressure-lowering effect and a similar reduction of the media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular collagen content was reduced and metalloproteinase-9 was increased by candesartan, but not by enalapril. Changes of circulating indices of collagen turnover and circulating matrix metalloproteinase paralleled those of vascular collagen. The 2 drugs equally improved endothelial function. In conclusion, antihypertensive treatment with drugs that inhibit the renin-angiotensin-aldosterone system activity is able to correct, at least in part, alterations in small resistance artery structure in hypertensive patients with NIDDM. Candesartan may be more effective than enalapril in reducing collagen content in the vasculature.", "Microalbuminuria predicts early mortality and renal disease in non-insulin-dependent diabetic patients. In insulin-dependent diabetic patients, angiotensin converting enzyme inhibition decreases microalbuminuria and retards the progression of renal disease. The aim of this study was to evaluate the effect of low dose ramipril on albumin excretion rate (AER) and blood pressure in non-insulin-dependent diabetic patients with persistent microalbuminuria (AER > 20 < 200 micrograms/min) and normal blood pressure or mild hypertension. The study was a randomized, double-blind, placebo-controlled clinical trial of 6 months duration at 14 hospital-based diabetes centers in northeastern Italy. Blood pressure, plasma glucose, and body weight were determined every month; AER, serum creatinine, glycosylated hemoglobin, and plasma lipids at baseline, after 1 month, and at the end of the study. Of 122 non-insulin-dependent diabetic patients randomly allocated in blocks of four to receive either ramipril (1.25 mg/day) or placebo, 108 (54 in the ramipril group and 54 in the placebo group) completed the study. At baseline, age, duration of diabetes, body mass index, and glycosylated hemoglobin were similar in the two groups and remained unchanged throughout the study. In the placebo group, AER rose from a baseline median of 65 micrograms/min (range 53 to 76, 95% confidence Interval) to 72 micrograms/min (57 to 87) and to 83 micrograms/min (62 to 104) after 1 and 6 months, respectively, but fell from 62 micrograms/min (48 to 76) to 45 micrograms/min (33 to 57) and to 53 micrograms/min (38 to 69), respectively, in the ramipril group, a significant difference between the groups (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)", "To assess whether inhibition of angiotensin converting enzyme protects kidney function in diabetic nephropathy.\n Open, randomised follow up study of normotensive insulin dependent diabetics with nephropathy either treated or not with captopril for one year.\n Outpatient diabetic clinic in a tertiary referral centre.\n 32 Normotensive patients with insulin dependent diabetes complicated by nephropathy who were randomised either to the treatment group (n = 15) or to the control group (n = 17).\n The treatment group was given captopril (25-100 mg/day) for 12 months, the average dose during the second six months of the study being 40 mg daily. Controls were not treated.\n Albuminuria, arterial blood pressure, and the glomerular filtration rate.\n Mean arterial blood pressure fell by 3 (SE 2) mm Hg in the captopril treated group and rose by 6 (1) mm Hg in the controls. In addition, albuminuria declined by 11% in the captopril treated group and rose by 55% in the controls, fractional albumin clearance fell by 17% in the captopril treated group and increased by 66% in the controls, and the glomerular filtration rate declined by 3.1 (2.8)ml/min/1.73 m2 with captopril and by 6.4 (3.1) ml/min/1.73 m2 in the controls.\n Inhibition of angiotensin converting enzyme arrests the progressive rise in albuminuria in normotensive insulin dependent diabetics with nephropathy.", "To assess the efficacy of an angiotensin converting enzyme (ACE) inhibitor (perindopril), a dihydropyridine calcium channel blocker (sustained release nifedipine) and placebo in preventing the progression of albuminuria and decline in glomerular filtration rate (GFR) in patients with Type 2 diabetes and microalbuminaria.\n A prospective, randomized, open, blinded end point study of 77 patients allocated to three treatment groups (23 perindopril, 27 nifedipine, 27 placebo). Drug doses were adjusted to achieve a decrease in diastolic blood pressure (DBP) of 5 mmHg in the first 3 months and additional therapy was given if hypertension developed (supine DBP > 90 mmHg and/or systolic blood pressure (SBP) > 140 mmHg if < or = 40 years; supine DBP > 90 mmHg and/or SBP > 160 mmHg if > 40 years). Median follow-up was 66 months, with 37 patients being followed for at least 6 years.\n Blood pressure remained within the non-hypertensive range in 83% of perindopril-, 95% of nifedipine- and 30% of placebo-treated patients (P < 0.01). In the first 12 months albumin excretion rate (AER) decreased by 47% only in the perindopril group (P = 0.04). From 12 to 72 months, AER gradients increased by 27% per year only in the placebo group (P < 0.01). After 6 years, macroalbuminuria had developed in 7/15 placebo compared with 2/11 in perindopril and 1/11 nifedipine-treated patients (P = 0.05). GFR did not change in the first 12 months, but thereafter the median GFR gradient (ml/min/1.73 m(2) per year) was -2.4 (P < 0.01) for perindopril-, -1.3 (P = 0.26) for nifedipine- and -4.2 (P = 0.01) for placebo-treated patients. The rate of decline in GFR for the study group as a whole from 12 months to the end of follow-up correlated negatively with mean arterial pressure (MAP) (r = -0.38, P < 0.01). During a 3-month treatment pause in 29 patients AER tended to increase only in the perindopril group (P < 0.07).\n Long-term control of blood pressure with perindopril or nifedipine stabilizes AER and attenuates GFR decline in proportion to MAP in non-hypertensive patients with Type 2 diabetes and microalbuminuria.", "To investigate whether a low dose of the angiotensin converting enzyme (ACE) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria.\n Randomised, double blind, parallel group trial comparing ramipril (1.25 mg/day) with placebo (on top of usual treatment) for cardiovascular and renal outcomes for at least three years.\n Multicentre, primary care study conducted mostly by general practitioners in 16 European and north African countries.\n 4912 patients with type 2 diabetes aged >50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria (urinary albumin excretion > or = 20 mg/l in two consecutive samples), and serum creatinine < or = 150 micromol/l.\n The primary outcome measure was the combined incidence of cardiovascular death, non-fatal myocardial infarction, stroke, heart failure leading to hospital admission, and end stage renal failure.\n Participants were followed for 3 to 6 (median 4) years. There were 362 primary events among the 2443 participants taking ramipril (37.8 per 1000 patient years) and 377 events among the 2469 participants taking placebo (38.8 per 1000 patient years; hazard ratio 1.03 (95% confidence interval 0.89 to 1.20, P = 0.65)). None of the components of the primary outcome was reduced. Ramipril lowered systolic and diastolic blood pressures (by 2.43 and 1.06 mm Hg respectively after two years) and favoured regression from microalbuminuria (20-200 mg/l) or proteinuria (> 200mg/l) to normal level (< 20 mg/l) or microalbuminuria (P < 0.07) in 1868 participants who completed the study.\n Low dose (1.25 mg) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria, despite a slight decrease in blood pressure and urinary albumin. The cardiovascular benefits of a daily higher dose (10 mg) ramipril observed elsewhere are not found with an eightfold lower daily dose.", "The aim of this study is to compare the efficacy of an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium channel blocker in preventing progression to macroalbuminuria and/or a decline in renal function in normotensive patients with type 1 diabetes and microalbuminuria. Forty-two patients were randomized to treatment with either perindopril, slow-release nifedipine, or placebo. In the first 3 months, drug dosage was titrated to achieve a decrease in diastolic blood pressure of at least 5 mm HG: Thirty-three patients had a minimum of 24 months' data, and 25 patients were followed up beyond 36 months (mean, 67 +/- 4 months). Patients were studied every 3 months and at the end of the treatment period; those who remained normotensive discontinued therapy and were followed up for an additional 3 months. Baseline geometric mean albumin excretion rates (AERs) were as follows: perindopril, 66 microg/min; nifedipine, 59 microg/min; and placebo, 66 microg/min. During the first 3 years, 7 of the perindopril-treated but none of the placebo or nifedipine-treated patients reverted to normoalbuminuria (P < 0.01). Median AERs at 3 years of treatment in each group were 23 microg/min for perindopril, 122 microg/min for nifedipine, and 112 microg/min for placebo patients (P < 0.01). In patients with more than 3 years' follow-up, median AERs decreased by 45% in the first year and then stabilized in the perindopril group, but increased by 17.6% in the nifedipine group and 27.6% in the placebo group (P < 0.03) in the first year, then increased progressively. In these same patients, there was a significant decline in glomerular filtration rate in the nifedipine group (-7.8 +/- 1.8 mL/min/1.73 m(2)/y), but not in the other two groups (perindopril, -1.0 +/- 1.2 mL/min/1.73 m(2)/y; placebo, -1.3 +/- 1.1 mL/min/1.73 m(2)/y; P = 0.004). At the end of the study, cessation of treatment for 3 months was associated with a doubling of AERs in the perindopril-treated group, but no change in the other two groups (P < 0.001). In conclusion, long-term perindopril therapy is more effective than nifedipine or placebo in delaying the progression of diabetic nephropathy and reducing AER to the normoalbuminuric range (<20 microg/min) in normotensive patients with type 1 diabetes and microalbuminuria.", "Recent studies utilizing converting enzyme inhibitors (CEI) in diabetic rats document reductions in both renal hypertrophy and albuminuria. Four separate clinical studies in normotensive patients with diabetes demonstrate reduction of microalbuminuria with CEIs independent of blood pressure reduction. The present pilot study examines the results of reducing an elevated glomerular filtration rate on changes in renal size and microalbuminuria in normotensive, hyperfiltering insulin-dependent diabetic (IDDM) patients. Fifteen IDDM patients were randomized to either placebo or the CEI, lisinopril. Dosage of lisinopril was titrated over 3 months to reduce glomerular filtration rate (GFR) to < or = 2.33 mL/sec. Evaluation at 18 months demonstrated the lisinopril group had a marked reduction in renal size (16.9 +/- 1.1, baseline versus 12.8 +/- 0.9 cm, 18 months; p < 0.05) and microalbuminuria (92 +/- 11 micrograms/min, baseline versus 23 +/- 26 micrograms/min, 18 months; p < 0.05). No change in renal size was noted in the placebo group (15.4 +/- 0.8, baseline versus 14.9 +/- 0.7 cm, 18 months; NS) and albuminuria increased (118 +/- 15 micrograms/min, baseline versus 293 +/- 32 micrograms/min, 18 months; p < 0.05). Mean arterial pressure at 18 months was significantly lower in the lisinopril group compared to placebo (102 +/- 4, placebo versus 87 +/- 6 mm Hg, CEI, p < 0.05). This study supports previous animal studies that document reductions in both microalbuminuria and renal size by a CEI. The overall impact of these findings on preservation of renal function cannot be assessed, however, in this short-term study.", "We previously reported that the angiotensin II type 1 receptor antagonist candesartan was effective in reducing blood pressure and microalbuminuria in hypertensive patients with diabetic nephropathy after angiotensin-converting enzyme (ACE) inhibitors were replaced due to side effects. In the present study, the clinical effects of candesartan were investigated and compared with ACE inhibitors in patients with stage 2 or 3A diabetic nephropathy, mainly with respect to the effects on the urinary excretion of albumin and type IV collagen.\n Forty-nine patients (26 males/23 females) with diabetic nephropathy (stage 2 or 3A), including normotensive patients, were the study subjects. The patients were treated with either an ACE inhibitor (23 patients) or candesartan (26 patients) for 11 +/- 3 months. The urinary excretion of albumin and urinary type IV collagen was measured.\n Posttreatment blood pressure tended to decrease, but such a decrease did not reach a statistically significant level, nor did it show any intergroup difference. The urinary albumin excretion was positively correlated with pretreatment mean blood pressure and left ventricular mass index, but the urinary type IV collagen excretion did not show such correlations. The urinary albumin excretion decreased significantly after treatment to a similar extent in both groups, whereas the urinary type IV collagen excretion decreased significantly only in the candesartan group.\n It was revealed that ACE inhibitors and candesartan reduced urinary albumin excretion to a similar extent in patients with diabetic nephropathy. From the results of the present study, it is inferred that the renoprotective effect of candesartan in diabetic nephropathy may partially differ from that of ACE inhibitors.", "Intervention trials on renal function in IDDM patients with microalbuminuria (MA) should adopt the rate of decline of glomerular filtration rate (GFR) as an outcome measure. However, normotensive IDDM patients with MA show no change in GFR over a follow-up period of 10 years. Thus, in the present study, we used the cumulative incidence of progression to albuminuria (albumin excretion rate [AER] > 200 micrograms/min) from MA as the primary endpoint and the yearly increase in AER at a rate of 50% above baseline as the secondary end-point of renal function.\n Ninety-two normotensive IDDM patients underwent double-blind, double-dummy treatment with either lisinopril or slow-release nifedipine in comparison with placebo. Ten patients discontinued the study during the 3-year follow-up period.\n During the 3-year follow-up period, 7 of 34 placebo-treated (20.6%), 2 of 32 lisinopril-treated (6.3%), and 2 of 26 nifedipine-treated (7.7%) patients progressed to clinical albuminuria (Fisher's exact test, P < 0.03). Time-to-event analysis indicated a reduction in the risk of progression to macroalbuminuria of 58.1% (95% CI 27.8-68.4%) in the 32 patients on lisinopril (P < 0.02) and of 62.5% (95% CI 32.5-73.4%) in the 26 patients on nifedipine (P < 0.02) after adjustment for mean blood pressure, glycated hemoglobin, and baseline AER in comparison with the 34 patients on placebo. Baseline AER was 71 micrograms/min (range: 20.7-187.3) in progressors and 73 micrograms/min (range: 20.2-174.1) in nonprogressors (NS). The percentage of patients who showed a > 50% yearly increase of AER above baseline values was significantly lower in the lisinopril group (13 of 32, 40.6%, P < 0.02), but not in the nifedipine group (15 of 26, 57.7%), than in the placebo group (23 of 34, 67.6%). The lisinopril group had significantly lower blood pressure values during follow-up than either the nifedipine (P < 0.05) or the placebo (P < 0.01) group.\n Our data show that both lisinopril and nifedipine are effective in delaying the occurrence of macroalbuminuria in normotensive IDDM patients with MA. As overt proteinuria strongly predicts end-stage renal failure, both treatments appear capable of preventing such a complication in normotensive IDDM patients with MA. However, lisinopril appears more powerful in slowing the course of nephropathy.", "Diabetes mellitus is a strong risk factor for cardiovascular and renal disease. We investigated whether the angiotensin-converting-enzyme (ACE) inhibitor ramipril can lower these risks in patients with diabetes.\n 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation study, aged 55 years or older, who had a previous cardiovascular event or at least one other cardiovascular risk factor, no clinical proteinuria, heart failure, or low ejection fraction, and who were not taking ACE inhibitors, were randomly assigned ramipril (10 mg/day) or placebo, and vitamin E or placebo, according to a two-by-two factorial design. The combined primary outcome was myocardial infarction, stroke, or cardiovascular death. Overt nephropathy was a main outcome in a substudy.\n The study was stopped 6 months early (after 4.5 years) by the independent data safety and monitoring board because of a consistent benefit of ramipril compared with placebo. Ramipril lowered the risk of the combined primary outcome by 25% (95% CI 12-36, p=0.0004), myocardial infarction by 22% (6-36), stroke by 33% (10-50), cardiovascular death by 37% (21-51), total mortality by 24% (8-37), revascularisation by 17% (2-30), and overt nephropathy by 24% (3-40, p=0.027). After adjustment for the changes in systolic (2.4 mm Hg) and diastolic (1.0 mm Hg) blood pressures, ramipril still lowered the risk of the combined primary outcome by 25% (12-36, p=0.0004).\n Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes. The cardiovascular benefit was greater than that attributable to the decrease in blood pressure. This treatment represents a vasculoprotective and renoprotective effect for people with diabetes.", "A 5-year randomized, double blind, placebo-controlled study was carried out to determine the effect of the angiotensin-converting enzyme (ACE) inhibitor enalapril (E) on the progress of renal function and histology in subjects with type 1 diabetes and microalbuminuria. Seventy three type 1 diabetic patients with BP <140/90 and with persistent albuminuria (AER 20-200 microg/min) and normal renal function were randomly assigned to receive E (n=37) or placebo (n=36). A percutaneous renal biopsy was successfully performed in 69 patients and repeated in 59 patients after 5 years. The mean glomerular volume (MGV), mesangial volume (Vv mes) and glomerular basement membrane thickness (GBMT) were measured histomorphometrically. Before treatment, both groups had similar clinical characteristics, blood pressure, HbA(1c), albumin excretion rate (AER), glomerular filtration rate (GFR), serum creatinine and renal structural damage. Blood pressure was well controlled in both groups. In the patients treated with E, albuminuria decreased significantly (P<0.05) and only 8.1% (3/37) of subjects progressed to clinical albuminuria (AER >300 mg/24 h) compared with 30.5% (11/36) in the placebo group. The E treatment resulted in absolute risk reduction of 22.4 percentage points for the development of clinical albuminuria over a 5-year period (P<0.01). After 5 years of treatment, GBM thickness showed a consistent, though statistically insignificant, increase in the placebo group, whereas it remained stable in the E group. A significant increase in MGV and Vv mes was also observed in the placebo group on completion of the study. The present study indicates that long term therapy with E may decrease or delay the progression of structural glomerular damage in microalbuminuric diabetic subjects without marked hypertension (BP <140/90).", "Normotensive type 1 diabetics with persistent albuminuria were randomized between 12 months' treatment with low-dose fosinopril (10 mg/d) and placebo in a 24-month, double-blind, crossover trial. Metabolic and cardiovascular variables were measured every three months and two-dimensional and M-mode echocardiography was performed before and after each treatment phase. Low-dose fosinopril led to 70% reduction in urinary albumin excretion (UAE) (220 +/- 199 vs 82 +/- 67 mg/24-h, p < 0.05), but UAE did not change during placebo treatment; the maximal change became apparent after 3 months and was reversible once treatment was stopped. Even though blood pressure (BP) did not change during fosinopril treatment, there was a significant correlation between baseline UAE and diastolic BP (r = 0.77, p = 0.027) and between change in UAE and change in systolic BP (r = 0.84, p = 0.01). The change in UAE approached borderline significance in correlation with the change in triglyceride concentration (r = 0.66, p = 0.07). Low-dose fosinopril favorably affects the \"cardiorenal syndrome\" seen in type 1 diabetics with persistent microalbuminuria.", "To assess if low (1.25 mg) and/or standard (5 mg) doses of the ACE inhibitor ramipril could prevent progression of microalbuminuria (incipient diabetic nephropathy) in normotensive type 1 diabetic patients.\n This study, using a multicenter randomized placebo-controlled double-blind parallel group, was conducted over 2 years in 28 outpatient diabetic clinics in the U.K. and Ireland. We screened 334 type 1 diabetic patients with suspected microalbuminuria and normal blood pressure; of these, 140 patients 18-65 years of age with a diagnosis of type 1 diabetes and persistent microalbuminuria, defined as urinary albumin excretion rate (AER) of 20-200 microg/min, were enrolled in the study.\n The proportion of patients progressing to macroalbuminuria was reduced in the ramipril groups but did not reach statistical significance over 2 years. AER was significantly lower at year 2 in the combined ramipril-treated patients versus placebo (P = 0.013). More patients on ramipril regressed to normoalbuminuria (<20 microg/min), with 11% for 1.25 mg ramipril, 20% for 5 mg ramipril, and 4% for placebo (P = 0.053). Blood pressure was significantly reduced to a similar extent with both 1.25 and 5 mg ramipril. Supine systolic blood pressure increased from 130 to 134 mmHg in the placebo group and fell in the 1.25 mg ramipril group (from 132 to 129 mmHg) and in the 5 mg ramipril group (from 134 to 130 mmHg) (P = 0.003, compared with placebo). No statistically significant changes were observed in glomerular filtration rate (GFR) between the placebo- and ramipril-treated groups during the 2-year period.\n Microalbuminuria is reduced significantly by ramipril treatment in type 1 diabetic patients without hypertension. Although the magnitude of the response was greater, there is no significant difference between responses to 1.25 or 5 mg ramipril. Small but highly significant reductions in systolic and mean arterial pressures occur in ramipril-treated patients. GFR is stable at this stage of the evolution of diabetic nephropathy and is unaffected by ramipril treatment for 2 years.", "This study was designed to compare the short-term (1-y) tolerability and antiproteinuric efficacy of enalapril and valsartan in patients with type 2 diabetes. Forty-two patients with normal renal function or early-stage nephropathy were recruited in Hong Kong and randomized to valsartan 80 mg/day or enalapril 5 mg/day; the doses were increased to 160 mg and 10 mg daily, respectively, as tolerated. Early-morning urine was analyzed for albumin and creatinine and 24-hour urinary albumin excretion at baseline and 1 year after therapy began. Twenty-two patients were randomized to valsartan and 20 to enalapril. The 2 treatment groups were similar in terms of age, sex distribution, and duration of diabetes or hypertension. Blood pressure decreased to a similar extent (-2.5% to -5.0%) with each drug. Similarly, the 24-hour urinary albumin excretion decreased by 5% to 6% with each drug. The albumin-creatinine ratio in early-morning urine samples and plasma creatinine levels decreased in the valsartan group and increased in the enalapril group, but the difference was not significant. Plasma potassium levels were stable in both groups at the end of study. Cough was reported by 7 (35%) patients receiving enalapril and none of those receiving valsartan (P=.003). In conclusion, enalapril and valsartan both reduced blood pressure and albuminuria to a similar extent with 1 year of therapy in Chinese patients with type 2 diabetes and normal renal function or early-stage nephropathy. Fewer adverse events were reported with valsartan, but both drugs appear to be relatively safe.", "Angiotensin-converting enzyme (ACE) inhibitors are known to reduce urinary albumin excretion (UAE) in diabetic patients. Animal studies have shown that, besides diminishing the glomerular capillary pressure, ACE inhibitors might reduce albuminuria by influencing glomerular charge selectivity through glomerular preservation of heparan sulphate proteoglycan. In humans, an indirect measurement of glomerular charge selectivity can be obtained by calculating the glomerular charge selectivity index (SI), a clearance ratio of IgG/IgG4, two identically sized but differently charged molecules. The aim of the present study was to evaluate the effect of ACE inhibition on charge selectivity by comparing SI in type I (insulin-dependent) diabetic patients with microalbuminuria after 6 years of treatment either with or without captopril. Thirty-five of 45 patients participating in a prospective randomized study evaluating the effect of captopril in preventing the development of diabetic nephropathy were included in the present study, 17 being treated with captopril, 18 left as untreated controls. The selectivity index was calculated after measuring s-IgG, u-IgG, s-IgG4, and u-IgG4. The results demonstrated a higher selectivity index in the captopril-treated group [1.21 (0.51-1.94) median (range)] compared to the control group [0.94 (0.31-1.87)], however, the difference was not statistically significant (p = 0.16). A negative correlation between the selectivity index and UAE was demonstrated in the captopril-treated group (r = -0.77; p = 0.0004), whereas the correlation in the control group did not reach statistical significance (r = -0.3; p = 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)", "The primary results of a three-year prospective, double-blind, placebo-controlled trial in non-insulin-dependent diabetic (NIDDM) patients show that an anti-hypertensive regimen, which includes the ACE inhibitor enalapril, preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors (J Am Soc Nephrol 3:335, 1992). The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis. Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [baseline glomerular filtration rate (GFR) 30 to 100 ml/min/1.73 m2]. Twenty-four hour urinary excretion of albumin (UAE), protein, urea nitrogen, creatinine and isotopically determined GFR were measured at baseline and six month intervals. Glycemic control and blood pressure regulation were assessed every three months. The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline (UAE > 300 mg/24 hr) as compared to patients with baseline sub-clinical proteinuria (UAE < or = 300 mg/24 hr). Antihypertensive treatment with enalapril preserved GFR significantly better (P < 0.01) in the patients with sub-clinical proteinuria at baseline (UAE < or = 300 mg/24 hr) than other antihypertensive treatments which excluded the ACE inhibitor. Furthermore, only 7% of the enalapril-treated group progressed to clinical albuminuria compared to 21% of control treated patients. Although the enalapril-treated group had a lower mean blood pressure during the maintenance period, no correlation between blood pressure (systolic, diastolic or mean arterial) and rate of change of GFR was observed.(ABSTRACT TRUNCATED AT 250 WORDS)", "1. Some non-insulin-dependent (type II) diabetic patients show albuminuria without arterial hypertension. In these patients, angiotensin-converting enzyme inhibitors reduce urinary albumin excretion without producing any changes in systemic blood pressure and renal haemodynamics. However, up to now it has not been clear whether these favourable renal effects are specifically related to angiotensin-converting enzyme inhibition or not. 2. Twelve type II diabetic outpatients with persistent macroalbuminuria (greater than 300 mg/daily on at least three consecutive occasions), without any other signs of renal disease and whose blood pressure was persistently below 140/90 mmHg, were studied. 3. In a randomized sequence and in a double-blind fashion, after a 2-month run-in period, patients were allocated to receive 5 mg of enalapril or 50 mg of atenolol daily for the next 6 months. At the end of this first period and after 6 months on placebo in a cross-over fashion, active treatment was replicated. Blood pressure and urinary albumin excretion were measured every 2 months, whereas the other variables studied were determined at the end of each period. 4. Kidney function and blood pressure did not change significantly, whereas albuminuria decreased significantly, after both of the drugs. 5. These data suggest that the inhibition of tissue angiotensin formation and the consequent reduction in glomerular permeability, rather than changes in renal and systemic haemodynamics, are the common mechanisms by which both enalapril and atenolol decreased albuminuria in our patients.", "Microangiopathy characterizes both diabetic retinopathy and nephropathy. It is currently unclear which diabetic subjects should be treated with angiotensin-converting enzyme (ACE) inhibitors. A double-blind, placebo-controlled protocol was implemented using captopril to treat subjects with Type I diabetes, early diabetic nephropathy (albumin excretion rates, 20-200 micrograms/min), and normal blood pressures. After two years, the final eye grades were improved in two treated subjects but not in any of the controls. Three control and one treated subject showed worsening of their eye grade after two years (P < .001, by chi-square test). Significant differences in renal albumin excretion were not seen between the two groups. The distribution of changes in retinal grades in the treatment group compared with the placebo group was improved after two years. Studies of larger numbers of patients will be necessary to determine if ACE inhibitors should be used routinely in subjects with diabetic retinopathy and to determine which subjects are most likely to respond.", "We compared the efficacy of treatment protocols with an angiotensin converting enzyme (ACE) inhibitor alone (enalapril, 5 mg) or angiotensin II (ATII) receptor blocker (losartan, 50 mg) or both enalapril plus losartan in patients with microalbuminuria in a prospective, randomized clinical trial. Normotensive type 2 diabetic patients with microalbuminuria documented by at least 3 consecutive urinary albumin excretion analyses were recruited for the study. Patients were grouped randomly into one of the protocols which consisted of treatment with 5 mg enalapril daily (group 1; n=12), 50 mg losartan daily (group 2; n=12) or both drugs (group 3; n=10). They were reevaluated with regard to HbA1c levels, lipid profiles, blood pressure and urinary albumin excretion rates (UAER) at 3-month intervals for 12 months. Mean age, duration of diabetes, body mass index, plasma lipid profiles and blood pressure levels were similar at the initial visit. In group 1, UAER returned to normal levels in 10 patients. Normalization of UAER occurred in 8 and 7 patients in groups 2 and 3, respectively. Percentage of reduction in UAERs at the end of 12 months were 58%, 59% and 60% (p=0.0001; p=0.0002; p=0.0003, respectively). The amount of reduction in UAER did not differ significantly among the three groups (p=0.346). ACE inhibitors and angiotensin II receptor blockers have similar efficacy in treating diabetic microalbuminuria, and the combination of the two drugs does not add any further benefit.", "Microalbuminuria is associated with dysfunction of the vascular endothelium in patients with diabetes mellitus. The objective of the present study was to determine whether treatment with losartan at a dose sufficient to lower urinary albumin excretion was accompanied by an improvement in endothelial function in type 2 diabetic patients with microalbuminuria.\n Endothelial function was measured in 80 type 2 diabetic patients with microalbuminuria and 68 non-diabetic controls using high-resolution vascular ultrasound. The diabetic patients were randomised to receive either losartan 50 mg daily or placebo in a 6-month double-blind study. Urinary albumin excretion and endothelial function were assessed at baseline, 3 and 6 months.\n Both endothelium-dependent (p<0.01) and -independent vasodilation (p<0.01) were significantly impaired in diabetic patients with or without history of hypertension compared to the non-diabetic controls. At baseline, the losartan- and placebo-treated groups were comparable in their clinical characteristics. Blood pressure did not change significantly in either group throughout the study. Urinary mean albumin excretion rate (MAER) decreased in the losartan-treated group (p<0.01) whereas an increase was observed in the placebo group (p<0.05). At 6 months, the losartan-treated group had significantly lower MAER than the placebo-treated group [54.5 (58.3) vs 78.5 (100.5) microg/min, p<0.05; median (interquartile range)]. No significant differences were found in endothelium-dependent or -independent vasodilation.\n Type 2 diabetic patients with microalbuminuria have impaired endothelium-dependent and -independent vasodilation. Treatment with low-dose losartan is sufficient to reduce microalbuminuria in these patients without alteration in endothelial function and systemic blood pressure.\n Copyright 2002 John Wiley & Sons, Ltd.", "To determine whether angiotensin-converting enzyme (ACE) inhibition with captopril reduces the progression of microalbuminuria to overt proteinuria in normotensive patients with insulin-dependent diabetes mellitus (IDDM).\n This study was a prospective randomized, double-blind, placebo-controlled trial involving 26 centers in the United States and Canada. One hundred forty-three subjects, 14 to 57 years of age, with IDDM for 4 to 33 years, blood pressure < 140/90 mm Hg in the absence of antihypertensive therapy, and persistent albumin excretion 20 to 200 micrograms/min were randomized to double-blind treatment with captopril 50 mg or placebo BID. Albumin excretion rate (AER), blood pressure, and glycohemoglobin were determined every 3 months, and creatinine clearance (CrCl) and urea excretion were measured every 6 months.\n Within 24 months, 6.0% (4/67) of captopril-treated subjects and 18.6% (13/70) of placebo-treated subjects progressed to clinical proteinuria, defined as AER > 200 micrograms/min and at least 30% above baseline (risk reduction = 67.8%, P = 0.037). AER increased at an annual rate of 11.8% (95% confidence interval [CI] -3.3% to 29.1%) in the placebo group, while it declined by 17.9% (CI -29.6% to -4.3%) in the captopril group (P = 0.004). CrCl decreased by 4.9 mL/min per 1.73 m2 per year in the placebo group, while it remained stable in the captopril group (0.9 mL/min per 1.73 m2 per year, P = 0.039 between groups). Ten subjects required treatment for hypertension; 8 in the placebo group and 2 in the captopril group. There was little correlation between the 24-month changes in mean arterial blood pressure and AER in either group. Glycohemoglobin and urinary urea excretion did not differ between groups.\n After 24 months of therapy with captopril, compared with placebo, normotensive subjects with IDDM experienced significantly less progression of microalbuminuria to clinical proteinuria, reduced albumin excretion, and preserved CrCl rate. The ACE inhibitor, captopril, was well tolerated.", "This study determines the long-term efficacy of the ACE inhibitor, enalapril, in reducing the progression of microalbuminuria to clinical albuminuria in normotensive patients with type 2 diabetes.\n There were 103 normotensive type 2 diabetic patients with persistent albumin excretion rate (AER) 20-200 micrograms/min and normal renal function followed for 5 years in a prospective randomized single-blind placebo-controlled trial. AER, blood pressure, fasting plasma glucose, and HbA1 were measured very 3-4 months and glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary urea every 12 months.\n In the patients treated with enalapril, AER decreased from 55 +/- 33 to 20 +/- 59 micrograms/min (geometric mean +/- SD), whereas in the placebo group, AER increased from 53 +/- 31 to 85 +/- 90 micrograms/min after 5 years. Within 5 years, 7.7% (4/52) of enalapril-treated subjects and 23.5% (12/51) of placebo-treated subjects progressed to clinical albuminuria defined as AER > 200 micrograms/min and at least 34% above baseline (risk reduction = 66.7%, P < 0.001). AER increased at an annual rate of 12.3% (95% CI 9.8-14.9) in the placebo group, while it declined by 16.7% (95% CI -18.3 to -15.2) in the enalapril group (P < 0.001). In addition, 8 of the 12 placebo-treated patients had evidence of coronary artery disease. The rest of the parameters remained practically unchanged in the two groups.\n After 5 years of therapy with enalapril, compared with placebo, normotensive subjects with type 2 diabetes experienced significantly less progression of microalbuminuria to clinical albuminuria, reduced AER, and preserved GFR.", "To evaluate the long-term effect of angiotensin-converting enzyme inhibition on proteinuria and on the rate of decline in kidney function in patients with type II diabetes mellitus and microalbuminuria.\n Randomized, double-blind, placebo-controlled trial. Each patient was followed for 5 years.\n Six clinics for diabetes mellitus coordinated by a department of medicine in a university hospital in Israel.\n Ninety-four normotensive, type II diabetic patients with microalbuminuria and normal renal function.\n The patients were randomly assigned to receive enalapril, 10 mg per day, or placebo. Any increase in blood pressure was treated with long-acting nifedipine.\n Albuminuria, blood pressure, serum creatinine, fasting blood glucose, and glycosylated hemoglobin levels, every 3 to 4 months.\n In the patients treated with enalapril, albuminuria decreased from 143 +/- 64 (mean +/- SD) mg/24 h to 122 +/- 67 mg/24 h during the first year. Thereafter, we observed a slow increase to 140 +/- 134 mg/24 h after 5 years. In the placebo group, albuminuria increased from 123 +/- 58 mg/24 h to 310 +/- 167 mg/24 h after 5 years. (Difference in rate of change in proteinuria [P < 0.05]). Kidney function (expressed as mean reciprocal creatinine) declined by 13% in the placebo group and remained stable (-1%) in the enalapril group (P < 0.05). Control of blood glucose levels remained stable, in both groups, throughout the study. The mean blood pressure was stable in the enalapril group (initial group mean, 99 +/- 2.1 mm Hg; fifth-year mean, 100 +/- 3.2 mm Hg) and increased in the placebo group from an initial mean value of 97 +/- 3.2 mm Hg to 102 +/- 3.4 mm Hg at the end of the study period (P = 0.082).\n In normotensive patients with diabetes mellitus type II, the institution of angiotensin-converting enzyme inhibition during early stages of diabetic nephropathy results in long-term stabilization of plasma creatinine levels and of the degree of urinary loss of albumin. These effects are probably independent of the antihypertensive action of these agents.", "To determine whether long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor has a beneficial effect on the urinary microalbumin excretion and renal function in non-insulin-dependent diabetes mellitus (NIDDM) patients, enalapril (5 mg/day) was administered for 48 months.\n -Fifty-two patients with NIDDM who had persistent microalbuminuria in the range of 20-300 mg/24 h, serum creatinine < 106.1 microM (1.2 mg/dl), supine systolic blood pressure (BP) < 150 mmHg, supine diastolic BP < 90 mmHg, and HbA1c < 10% were divided into four groups. Twenty-six patients with normotension were divided at random into two groups; one group received enalapril (5 mg/day) (NE group), the other did not receive enalapril (NC group). In the same way, 26 other patients who were already well-controlled with nifedipine (30 mg/day) over a long-term period (4-6 years) were divided at random into two groups; one received enalapril (5 mg/day) (HE group), the other did not receive enalapril (HC group).\n After 48 months, urinary albumin excretion (UAE) was markedly reduced in group NE from 102.4 x/divided by 1.3 to 55.5 x/divided by 1.3 mg/24 h (P < 0.005), whereas no significant change occurred in group NC. In the well-controlled hypertensive groups, a significant reduction in UAE occurred in group HE (P < 0.05), whereas no significant change occurred in group HC. No changes in creatinine clearance, BP, or blood glucose control were seen during the study.\n Treatment with enalapril for 48 months may have a beneficial effect on the decline of microalbumin excretion in NIDDM patients.", "The effects of a long term reduction in blood pressure on the kidney function of normotensive diabetic patients who had persistent microalbuminuria (30-300 mg albumin/24 hours) were studied in two groups of 10 such patients before and during six months of treatment with either 20 mg enalapril or placebo daily. Treatments were assigned randomly in a double blind fashion. Before treatment both groups had similar clinical characteristics, weight, diet, total glycosylated haemoglobin, median albumin excretion rate (enalapril group 124 mg/24 h, placebo group 81 mg/24 h), and mean arterial pressure (enalapril group 100 (SD 8) mm Hg, placebo group 99 (6) mm Hg). During treatment weight, urinary urea excretion, and total glycosylated haemoglobin remained unchanged. The mean arterial pressure decreased in the enalapril group but not in the placebo group (enalapril group 90 (10) mm Hg, placebo group 98 (8) mm Hg). The median albumin excretion rate also fell in the enalapril group but not in the placebo group (enalapril group 37 mg/24 h, placebo group 183 mg/24 h.) The glomerular filtration rate rose in the enalapril group from 130 (23) ml/min/1.73 m2 to 141 (24) ml/min/1.73 m2, and total renal resistances and fractional albumin clearance decreased while fractional albumin clearance increased in the placebo group. These results show that in patients who have diabetes but not hypertension a reduction in blood pressure by inhibition of converting enzyme for six months can reduce persistent microalbuminuria, perhaps by decreasing the intraglomerular pressure.", "The ABCD (Appropriate Blood Pressure Control in Diabetes) Trial is a large, prospective, randomized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus (NIDDM) designed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in NIDDM. The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and an angiotensin-converting-enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations aged 40-74 years, 470 hypertensive patients (diastolic blood pressure of > or = 90.0 mmHg at time of randomization) and 480 normotensive patients (diastolic blood pressure of 80.0 mmHg at time of randomization). The study duration is 5 years and is scheduled to end in May of 1998. Patients are randomized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy. Patients are also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control is necessary. The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance. Secondary outcome measures are urinary albumin excretion, left ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity and mortality will also be evaluated. Given the data showing the impact of hypertension on complications in NIDDM, the ABCD Trial is designed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM.", "In the treatment of diabetic nephropathy, ACE inhibitor therapy reduces albumin excretion and slows the rate of decline in glomerular filtration rate (GFR). Our study was designed to investigate whether these effects lay in amelioration of the underlying glomerular structural abnormalities. A total of 54 type 1 diabetic patients with albuminuria and blood pressure (BP) <150/90 mmHg were randomized to receive 10 mg enalapril once daily, 10 mg nifedipine retard twice daily, or placebo in a multicenter double-blind study of 3 years' duration. Renal biopsy was performed at baseline and follow-up, and tissue was analyzed by standard morphometric methods. BP, GFR, albumin excretion rate (AER), and HbA1c were measured every 6 months. Enalapril lowered AER after 6 months by 26% (P < 0.05); however, this reduction was not sustained at 3 years. There was no significant effect of nifedipine or placebo on AER. GFR decreased by a similar average rate of 4.1 ml x min(-1) x year(-1) (95% CI 2.6-5.6) in all three groups. BP and HbA1c were unchanged throughout the study in all groups. At baseline, nearly all biopsies showed classic appearances of diabetic glomerulopathy. There was no detectable effect of enalapril compared with either nifedipine or placebo on renal structure over 3 years. However, we found that patients with increased AER have established glomerulopathy and a progressive average decline in GFR of 4.1 ml x min(-1) x year(-1) in the absence of overt hypertension, and baseline AER appeared predictive of subsequent mesangial volume fraction (r = 0.20, P = 0.0018). In this small cohort of nonhypertensive patients studied for 3 years, disease evolution appears unaffected by treatment with either enalapril or nifedipine.", "Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases.\n In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis.\n At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group.\n Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.", "to clarify and confirm the renoprotective effects of ACEIs in Japanese type 1 diabetics.\n a double-blind randomized study using two ACEIs, imidapril (a prodrug of imdaprilat without an SH-residue) and captopril as well as placebo was performed. Seventy-nine eligible cases were randomized to receive captopril 37.5 mg (n=26), imidapril 5 mg (n=26) or their placebos (n=27) daily in a double-blind manner.\n urinary albumin excretion (UAE), determined every half year, was significantly decreased by the ACEIs (placebo vs. ACEIs F=11.316, P=0.001, placebo vs. captopril F=4.260, P=0.043, placebo vs. imidapril F=14.341, P<0.001) during the study period (the mean; 1.48 years). Although the HbA(1C) levels and systolic blood pressure (BP) between the three groups were not different, glycemic and BP control significantly affected UAE. Systolic BP in the placebo group tended to be higher by 7-10 mmHg throughout the study.\n these results suggest that the ACE inhibitors, imidapril and captopril, prevent the increase in UAE in micro and macroalbuminuric patients with type 1 diabetes mellitus and that the target BP might be less than 130/80 mmHg.", "Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors in persons with type 2 diabetes.\n In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure; the rates of end-stage renal disease and cardiovascular events; and the rate of death from all causes.\n After five years, the change in the glomerular filtration rate was -17.5 ml per minute per 1.73 m2 (where the minus sign denotes a decrement) in the telmisartan-treated subjects, as compared with -15.0 ml per minute per 1.73 m2 in the enalapril-treated subjects; the treatment difference was thus -2.6 ml per minute per 1.73 m2 (95 percent confidence interval, -7.1 to 2.0 ml per minute per 1.73 m2)[corrected] The lower boundary of the confidence interval, in favor of enalapril, was greater than the predefined margin of -10.0 ml per minute per 1.73 m2, indicating that telmisartan was not inferior to enalapril. The effects of the two agents on the secondary end points were not significantly different after five years.\n Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes. These findings do not necessarily apply to persons with more advanced nephropathy, but they support the clinical equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events.\n Copyright 2004 Massachusetts Medical Society.", "To determine the effects of captopril on microalbuminuria and renal function in normotensive type II diabetic patients.\n A total of 26 patients were randomized in two homogeneous groups for clinical and analytical data in a 6-mo follow-up study. Group A received captopril (initial dose: 12.5 mg daily, increased according to tolerance); group B was untreated.\n Microalbuminuria decreased only in the treated group at 6 mo (P = 0.044) and a significant (P = 0.027) mean percentage change on microalbuminuria excretion between the groups was observed. Filtration fraction decreased in group A (baseline: 0.23 +/- 0.03; 6 mo: 0.22 +/- 0.04) and increased in group B (baseline: 0.22 +/- 0.04; 6 mo: 0.25 +/- 0.04) with a significant mean percentage change between the groups at 6 mo (P = 0.032). The mean percentage change in microalbuminuria was significantly correlated with a mean percentage change in diastolic blood pressure throughout the trial. Neither metabolic control nor sodium or protein intake changed in either group during the trial.\n These results suggest that captopril can help arrest microalbuminuria in normotensive type II diabetic patients, with a decrease in diastolic blood pressure and filtration fraction after a 6-mo treatment.", "To study the effect of Captopril on ambulatory blood pressure, renal and cardiac function and extracellular volume in microalbuminuric Type 1 diabetic patients.\n Randomized, double blind placebo controlled study of two years duration.\n University clinic.\n Twenty-two patients without hypertension.\n Patients received 50 mg Captopril or placebo twice a day.\n Ambulatory blood pressure, renal function, extracellular volume, and echocardiographic indices of cardiac function and dimensions were assessed annually. Clinic blood pressure and urinary albumin excretion were measured every 3 months.\n Twenty-four hour mean arterial blood pressure was unchanged in the Captopril group (mean +/- SD) (baseline 93 +/- 4 and follow up 91 +/- 8 mmHg) and in the placebo group (96 +/- 7 and 97 +/- 10 mmHg, NS). Night/day ratio of blood pressure was unaffected. Glomerular filtration rate was unchanged and renal plasma flow increased in the Captopril (557 +/- 97 and 600 +/- 112 ml min-1) versus the placebo group (574 +/- 85 and 535 ml min-1, p = 0.05). Filtration fraction was reduced in the Captopril versus the placebo group (p < 0.05). Extracellular volume and echocardiographically derived parameters were unaffected. The relative change in day time mean arterial blood pressure in the Captopril group correlated with changes in urinary albumin excretion (Spearmans r = 0.85, p < 0.05) unlike clinic mean arterial blood pressure (r = 0.33, p = 0.35).\n Diurnal rhythm of blood pressure was unaffected by long term administration of Captopril. Renal plasma flow was increased and filtration fraction reduced. A significant association between changes in urinary albumin excretion and blood pressure after Captopril was revealed only by the implementation of ambulatory blood pressure measurements.", "Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, placebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance >60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of nondiabetic nephropathy. The remaining 22 were randomized ( 11 to Perindopril [PE], 11 to placebo [PO]), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (+1562 mg/d) but declined in PE patients (-156 mg/d) (P < 0.05). Morphometric analysis was performed by light microscopy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 +/- 5.3 versus 40.2 +/- 11.1%; P = 0.001) but was unchanged in PE patients (33.8 +/- 4.9 versus 34.7 +/- 6.6%; P = 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril prevents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.", "It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure.\n We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration, the development of end-stage renal disease, or death from any cause. We also compared them with regard to the time to a secondary, cardiovascular composite end point.\n The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group (P=0.02) and 23 percent lower than that in the amlodipine group (P=0.006). The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group (P=0.003) and 37 percent lower in the irbesartan group than in the amlodipine group (P<0.001). Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups (P=0.07 for both comparisons). These differences were not explained by differences in the blood pressures that were achieved. The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group (P=0.008) and 21 percent more slowly than in the amlodipine group (P=0.02). There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point.\n The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of the reduction in blood pressure it causes.", "The purpose of this study was to assess whether long-term (8 years) inhibition of angiotensin-converting enzyme (ACE) protects kidney function in normotensive type 1 diabetic patients with diabetic nephropathy.\n We performed an open randomized follow-up study of normotensive type 1 diabetics with nephropathy either treated (N = 15) or not (N = 17) with captopril twice per day (average 74, range 12.5 to 125 mg/day). The main outcome measures were arterial blood pressure, albuminuria, and glomerular filtration rate (GFR; 51Cr-EDTA plasma clearance, twice yearly).\n Arterial blood pressure (mm Hg) was kept constant in the captopril group, at baseline (mean, SEM), 128/78 (3/2) and during follow-up 129/77 (4/1) but increased significantly in the control group from 127/79 (2/1) to 137/84 (5/2) (P < 0.01). Furthermore, 8 out of the 17 control subjects required treatment with blood pressure-lowering drugs because they developed hypertension. The fractional albumin clearance (x10-5) remained unchanged in the captopril group: baseline [10.8 (1.25) geometric mean and antilog (SEM)] during the eight years [11.8 (1.47)], while a significant rise occurred in control patients: 13.3 (1.23) to 26.2 (1.42) (P < 0.05). Baseline GFR was nearly identical: 111 (6) and 115 (4) mL/min/1.73 m2 in the captopril and control group, respectively. The median (range) rate of decline in GFR (mL/min/year) was 1.7 (10.7 to -2.0) in the captopril group versus 2.8 (17.7 to -2.6) in the control group (P = NS).\n The beneficial effect of captopril in arresting the rise in systemic blood pressure and albuminuria is long lasting. A loss in GFR is minimal in most patients with diabetic nephropathy if normotension is sustained by prospective treatment with ACE inhibitors or restored by implementation of other antihypertensive medications with the development of hypertension.", "Microalbuminuria and hypertension are risk factors for diabetic nephropathy. Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes, but similar data are lacking for hypertensive patients with type 2 diabetes. We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria.\n A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational, randomized, double-blind, placebo-controlled study of irbesartan, at a dose of either 150 mg daily or 300 mg daily, and were followed for two years. The primary outcome was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level.\n The base-line characteristics in the three groups were similar. Ten of the 194 patients in the 300-mg group (5.2 percent) and 19 of the 195 patients in the 150-mg group (9.7 percent) reached the primary end point, as compared with 30 of the 201 patients in the placebo group (14.9 percent) (hazard ratios, 0.30 [95 percent confidence interval, 0.14 to 0.61; P< 0.001] and 0.61 [95 percent confidence interval, 0.34 to 1.08; P=0.081 for the two irbesartan groups, respectively). The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group, 143/83 mm Hg in the 150-mg group, and 141/83 mm Hg in the 300-mg group (P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups). Serious adverse events were less frequent among the patients treated with irbesartan (P=0.02).\n Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria." ]

[ "15364042", "14643092" ]

[ "Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia.", "Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial." ]

[ "Lamotrigine, a novel anticonvulsant drug having modulatory effects on glutamatergic neurotransmission, improves mood and cognition parameters in bipolar disorder. Recent studies suggest that when added to clozapine, lamotrigine treatment may result in significant positive symptoms reductions in schizophrenia. Similar effects were not observed in an open trial in which lamotrigine was used as adjuvant to nonclozapine antipsychotics.\n Thirty-eight treatment-resistant schizophrenia inpatients receiving conventional and atypical antipsychotics enrolled in a 10-week, double-blind, placebo-controlled study, in which they were randomized in a 2:1 ratio to receive adjuvant treatment with lamotrigine, gradually titrated to a 400 mg/day dose, or placebo. Of these, 31 completed the trial. Measures of clinical efficacy and side effects were determined every other week. Serum levels of amino acids were assessed at the beginning and end of the study.\n In primary last observation carried forward analysis, no statistically significant between-group differences were observed; however, the completers' analyses revealed that lamotrigine treatment resulted in significant (p < or = .05) reductions in positive and general psychopathology symptoms, as measured by the Positive and Negative Syndrome Scale. No significant differences in lamotrigine effects were noted between conventional versus atypical antipsychotics. Lamotrigine treatment was well tolerated, and glutamate serum levels remained stable throughout the study.\n These preliminary findings 1) support the hypothesis that lamotrigine adjuvant treatment may improve positive symptoms and general psychopathology in schizophrenia, 2) suggest that beneficial effects may be achieved when lamotrigine is added to both conventional and atypical antipsychotics, and 3) warrant additional, larger scale trials.", "There is no evidence from randomized, controlled trials that demonstrate effectiveness for any pharmacological treatment in clozapine-resistant schizophrenia. Since the introduction of chlorpromazine, all antipsychotics with proven efficacy on positive symptoms have been dopamine antagonists, but recent experimental data suggest that ketamine-induced positive schizophreniform symptoms in healthy subjects can be controlled by a glutamate antagonist lamotrigine. The hypothesis tested was that lamotrigine is more effective than placebo in the treatment of positive schizophrenic symptoms when combined with clozapine.\n Thirty-four hospitalized treatment-resistant patients having chronic schizophrenia participated in a double-blind, placebo-controlled, 14-week, crossover trial where 200 mg/day lamotrigine was gradually added to their ongoing clozapine treatment. Clinical assessments were made by the Positive and Negative Syndrome Scale at the beginning and end of each treatment period.\n In intention-to-treat analysis, lamotrigine treatment was more effective in reducing positive (effect size.7, p =.009) and general psychopathological (effect size.6, p =.030) symptoms, whereas no improvement was observed in negative symptoms.\n These results provide the first evidence from a randomized controlled trial of an effective pharmacological treatment with an anticonvulsant agent in treatment-resistant schizophrenia and indicate that both positive and general psychopathological symptoms in patients with schizophrenia can be controlled by a drug that is not a dopamine antagonist. The results are in line with previous experimental data suggesting that excessive glutamate neurotransmission contributes to the positive symptoms of schizophrenia." ]

[ "8892714", "16353319", "8941062", "16278618", "3056498", "10740331", "11384629", "11910651", "15259284", "8429800", "9572210", "10739508", "16875644", "11974556", "12627044", "11387299", "1532445", "15259289", "10076125", "8861084", "11770191", "8569016", "8487239", "1929686", "12592236", "7772012", "12133397", "10515673", "11226444", "9089564", "11727357", "7936513", "12941676", "15259280", "8178840", "11731187", "16278615", "11910662", "2548135", "16294460", "16315025", "1536215", "12117397" ]

[ "The comparative effect on bone density, endometrium, and lipids of continuous hormones as replacement therapy (CHART study). A randomized controlled trial.", "Bleeding profile and endometrial safety of continuous combined regimens 1 mg 17beta-estradiol/trimegestone versus 1 or 2 mg 17beta-estradiol/norethisterone acetate in postmenopausal women.", "Comparison of two continuous combined estrogen progestogen regimens in postmenopausal women: a randomized trial.", "Oral hormone therapy with 17beta-estradiol and 17beta-estradiol in combination with norethindrone acetate in the prevention of bone loss in early postmenopausal women: dose-dependent effects.", "Comparison of four continuously administered progestogen plus oestradiol combinations for climacteric complaints.", "Piperazine oestrone sulphate and interrupted norethisterone: effects on the postmenopausal endometrium.", "Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate.", "Comparison of the efficacy and endometrial safety of two estradiol valerate/dienogest combinations and Kliogest for continuous combined hormone replacement therapy in postmenopausal women.", "A low-dose start in hormone replacement therapy provides a beneficial bleeding profile and few side-effects: randomized comparison with a conventional-dose regimen.", "A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment.", "Bleeding pattern and endometrial changes during continuous combined hormone replacement therapy. The Ogen/Provera Study Group.", "Optimizing continuous-combined hormone replacement therapy for postmenopausal women: a comparison of six different treatment regimens.", "Effects of tibolone and continuous combined conjugated equine estrogen/medroxyprogesterone acetate on the endometrium and vaginal bleeding: results of the OPAL study.", "Endometrial safety and bleeding patterns during a 2-year study of 1 or 2 mg 17 beta-estradiol combined with sequential 5-20 mg dydrogesterone.", "Comparison of the difference in histopathology and cell cycle kinetics among the postmenopausal endometrium treated with different progestins in sequential-combined hormone replacement therapy.", "A prospective randomized controlled study comparing two doses of gestodene in cyclic combined HRT preparations on endometrial physiology.", "Sequential estrogen and progestogen therapy: assessment of progestational effects on the postmenopausal endometrium.", "Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.", "Progestational effects of combinations of gestodene on the postmenopausal endometrium during hormone replacement therapy.", "17 beta-estradiol and norethisterone acetate in low doses as continuous combined hormone replacement therapy.", "Acceptability and patterns of endometrial bleeding in estradiol-based HRT regimens: a comparative study of cyclical sequential combinations of trimegestone or norethisterone acetate.", "Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial.", "Evaluation of low-dose estrogen and progestin therapy in postmenopausal women. A double-blind, prospective study of sequential versus continuous therapy.", "The effects of estrone (Ogen) on spinal bone density of postmenopausal women.", "A randomized, double-blind, placebo-controlled, multicenter study that assessed the endometrial effects of norethindrone acetate plus ethinyl estradiol versus ethinyl estradiol alone.", "Continuous combined piperazine oestrone sulphate and medroxyprogesterone acetate hormone replacement therapy--a study of bleeding pattern, endometrial response, serum lipid and bone density changes.", "[Comparative study on two different dosages of conjugated equine estrogen continuously combined with medroxyprogesterone in prevention of postmenopausal osteoporosis].", "Adverse endometrial effects during long cycle hormone replacement therapy. Scandinavian Long Cycle Study Group.", "Constant estrogen, intermittent progestogen vs. continuous combined hormone replacement therapy: tolerability and effect on vasomotor symptoms.", "HRT and exercise: effects on bone density, muscle strength and lipid metabolism. A placebo controlled 2-year prospective trial on two estrogen-progestin regimens in healthy postmenopausal women.", "A 1-year comparison of the efficacy and clinical tolerance in postmenopausal women of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone.", "Assessment of less than monthly progestin therapy in postmenopausal women given estrogen replacement.", "Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial.", "Endometrial safety and tolerability of triphasic sequential hormone replacement estradiol valerate/medroxyprogesterone acetate therapy regimen.", "Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group.", "Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: a randomized comparative dose-ranging study.", "Long-term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind, multicenter trial.", "Bleeding patterns and endometrial histology during administration of low-dose estradiol sequentially combined with dydrogesterone.", "A prospective 1-year study of estrogen and progestin in postmenopausal women: effects on the endometrium.", "A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women.", "Effects of two different regimens of continuous hormone replacement therapy on endometrial histopathology and postmenopausal uterine bleeding.", "Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women.", "Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial." ]

[ "To compare the effect of continuous norethindrone acetate (NA)-ethinyl estradiol (EE2) combinations with matching unopposed EE2 or placebo.\n A 2-year, double-blind, placebo-controlled, parallel-group clinical trial.\n Outpatients at 65 centers.\n Asymptomatic or mildly symptomatic women aged 40 years or older who had undergone the onset of spontaneous menopause within the last 5 years and who had an intact uterus.\n Patients were equally randomized to placebo or 1 of 8 treatment groups: 0.2 mg of NA and 1 microg of EE2; 0.5 mg of NA and 2.5 microg of EE2; 1 mg of NA and 5 microg of EE2; 1 mg of NA and 10 microg of EE2; 1 microg of EE2; 2.5 microg of EE2; 5 microg of EE2; or 10 microg of EE2.\n Bone mineral density (BMD) measured by quantitative computed tomography, serum lipids, and endometrial effects as assessed by rate of hyperplasia and proliferative status.\n Twelve hundred sixty-five patients entered the study. Bone mineral density increased significantly from baseline (P<.001) in the 1 mg NA-5 microg EE2 and the 1 mg NA-10 microg EE2 treatment groups at each annual assessment. Among the unopposed EE2 groups, only the 10-microg group had increased BMD above baseline, but also was accompanied by an unacceptably high rate of endometrial hyperplasia. The NA-EE2 treatment groups had a significant linear dose-response trend for increasing BMD. Increased endometrial proliferation and hyperplasia occurred with increasing unopposed estrogen doses. The combination of NA and EE2 effectively protected the endometrium against hyperplasia. The percentage of change in the ratio of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol was positive for all treatment groups. The increase in triglyceride levels associated with EE2 was attenuated with NA-EE2 treatment.\n Daily treatment with NA-EE2 was well tolerated and protected the endometrium from EE2-induced proliferation and hyperplasia. The NA-EE2 treatments produced a dose-related significant increase in BMD that was not present with unopposed EE2 treatment. The overall effect of NA-EE2 treatments on lipid measures was favorable.", "To compare the bleeding profile and endometrial safety of continuous combined 1 mg 17beta-estradiol (17beta-E2) and 0.125 mg trimegestone (TMG) with those of two continuous combined 17beta-E2 and norethisterone acetate (NETA) regimens.\n This was a double-blind, randomized, multicenter study conducted in 12 European countries and Israel over a 2-year period. Healthy postmenopausal women with an intact uterus were given either 1 mg 17beta-E2/0.125 mg TMG, 2 mg 17beta-E2/1 mg NETA or 1 mg 17beta-E2/0.5 mg NETA for up to 26 cycles, each of 28 days.\n The percentage of amenorrheic women was greater in most cycles up to cycle 13 in the 1 mg 17beta-E2/0.125 mg TMG group than in the comparator groups. The mean number of bleeding days was similar in the 1 mg 17beta-E2/0.125 mg TMG and the 1 mg 17beta-E2/0.5 mg NETA groups, but greater in the 2 mg 17beta-E2/1 mg NETA group. No endometrial hyperplasia was observed for any group.\n Continuous combined 1 mg 17beta-E2/0.125 mg TMG exhibits a more favorable bleeding profile than 1 mg 17beta-E2/0.5 mg NETA up to 1 year, while providing an adequate protective effect on the endometrium.", "To compare two different continuous regimens of estrogens: conjugated estrogens or estrone sulfate with medroxyprogesterone acetate (MPA). To evaluate the impact of these two regimens on bleeding pattern, endometrial histology, lipid metabolism, and climacteric symptoms.\n Prospective, open label, single center, randomized trial.\n The menopause clinic, Centre Universitaire de Santé de l'Estrie, Université de Sherbrooke, Quebec, Canada.\n Fifty-nine postmenopausal women seeking treatment for symptomatic menopause.\n Patients were randomized to two groups. Both groups received 2.5 mg/d MPA plus 0.625 mg/d conjugated estrogens (group A: 31 patients) or 0.625 mg/d estrone sulfate (group B: 28 patients). Lipid metabolism, endometrial biopsies, and endometrial thickness (measured by vaginal ultrasound) were determined at 52 and 104 weeks.\n Six women (10%) withdrew from the study (irregular bleeding and side effects). Fifty-three patients completed the study. Amenorrhea was produced in 92.6% and 96.1% by 52 weeks, and 100% by 104 weeks for groups A and B, respectively. Endometrial atrophy was observed by histology in 92.4% by 52 weeks and in 100% by 104 weeks in both groups. The correlation between an endometrial thickness (vaginal ultrasound) of < or = 4 mm and histologic diagnosis of endometrial atrophy was found in 41 of 53 patients. In both groups the climacteric symptoms were improved and the lipid profile showed a beneficial effect.\n No significant difference was found between the two continuous regimens. Amenorrhea and atrophic endometrium occurred in 92.4% after 52 weeks of treatment. A favorable change in lipid metabolism even with the addition of MPA to estrogens was noted. Irregular bleeding was reduced and the long-term compliance with the continuous regimen was high (90%).", "A 2-year multicenter, double-blind, randomized, placebo-controlled study examined the efficacy and safety of different doses of 17beta-estradiol (E(2)) alone and continuous-combined oral formulations of E(2) and norethindrone acetate (NETA) versus placebo in the prevention of bone loss in newly menopausal women.\n Patients were randomized to one of seven groups: placebo, E(2) 0.25 mg, E2 0.5 mg, E(2) 1 mg, E(2) 1 mg/NETA 0.25 mg, E(2) 1 mg/NETA 0.5 mg, or E(2) 2 mg/NETA 1 mg. Treatment was a once-daily tablet taken for 26 months. The primary efficacy endpoint was the change in bone mineral density (BMD) at the lumbar spine, measured by dual-energy x-ray absorptiometry, at screening and at 13, 19, and 26 months. BMD changes at the femoral neck and trochanter were also assessed. Biochemical markers of bone metabolism were measured at baseline, and at 3, 6, 13, 19, and 26 months. Histological diagnoses of endometrial samples were tabulated for each treatment group.\n A total of 327 women were randomized and 189 women completed the 2-year trial. BMD at the lumbar spine decreased 2.3% in the placebo group. The lowest dose of unopposed E(2) prevented bone loss at the spine and hip. Significant increases in spine BMD compared with placebo occurred in all groups of treatment with E(2) and were more pronounced in the combination groups. Compared with placebo, women receiving active treatment experienced greater reductions in bone resorption markers. The effects were evident by 6 months and generally remained stable thereafter. Adverse events, primarily associated with the endometrium, were the most common reasons for discontinuation.\n There is a dose-dependent effect of E(2) on BMD. The addition of NETA seems to enhance the response in BMD observed with E(2). Low doses of E(2) (1 mg and lower) can be considered for the prevention of osteoporosis, while titrating the hormone dose to individual patient's needs.", "Sixty women with climacteric complaints who had not menstruated for at least 1 year were randomly allocated to receive one of four hormonal replacement regimens. All four formulations were administered daily and continuously and each contained 2 mg of micronized oestradiol-17 beta in combination with either norethisterone acetate 1 mg (group A) or 0.5 mg (group B) or megestrol acetate 5 mg (group C) or 2.5 mg (group D). The clinical efficacy was the same although the alleviation of vasomotor symptoms was somewhat slower in those women receiving preparation A. The endometrium was atrophied in nearly all biopsies. Irregular uterine bleeding was almost entirely confined to the earlier phase of the study and was substantially less with the formulation containing 1 mg norethisterone acetate. It is concluded that a continuous oestradiol-progestogen combination can be used for long-term treatment of climacteric complaints in postmenopausal women and that after 4 months the clinical efficacy is the same irrespective of the type and dose of progestogen administered.", "To assess the effects on the postmenopausal endometrium of two doses of oral piperazine oestrone sulphate and interrupted norethisterone in comparison with a continuously combined regimen and placebo.\n A prospective randomised trial.\n Two hundred healthy postmenopausal women.\n Random assignment to two years of treatment with alternating three-day cycles of 1.5 mg piperazine oestrone sulphate and 1.5 mg piperazine oestrone sulphate + 0.7 mg norethisterone (highEP), or alternating three-day cycles of 0.75 mg piperazine oestrone sulphate and 0.75 mg piperazine oestrone sulphate + 0.35 mg norethisterone (lowEP), or 2 mg 17 beta-oestradiol continuously combined with 1 mg norethisterone acetate (E2+NETA), or placebo.\n Effect of treatment on endometrial histology, endometrial thickness, occurrence of uterine bleeding, endometrial oestrogen and progesterone receptor content, endometrial isocitrate dehydrogenase activity, and serum placental protein 14.\n The incidence of bleeding declined with time. In the second treatment year, the women receiving lowEP reported on average 7.3 days of bleeding, highEP 16.7 days, and E2+NETA 11.2 days. Histological assessment of endometrial biopsies revealed an atrophic or slightly secretory endometrium. Serum placental protein 14 increased slightly, but was statistically highly significant, during treatment, but no cyclical variation was observed. Endometrial isocitrate dehydrogenase was low in all three hormone groups and the same low level of endometrial oestrogen receptor and progesterone receptor was found comparable to the level in the placebo group.\n Histological and biochemical assessment of the endometrium showed that interrupted hormone replacement therapy induced the same pattern in endometrial parameters as continuous combined hormone replacement therapy.", "To evaluate the efficacy of lower doses of conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) for relieving vasomotor symptoms and vaginal atrophy.\n A randomized, double-blind, placebo-controlled trial (the Women's Health, Osteoporosis, Progestin, Estrogen study).\n Study centers across the United States.\n Two thousand, six hundred, seventy-three healthy, postmenopausal women with an intact uterus, including an efficacy-evaluable population (n = 241 at baseline).Intervention(s): Patients received for 1 year (13 cycles; in milligrams per day) CEE, 0.625; CEE, 0.625 and MPA, 2.5; CEE, 0.45; CEE, 0.45 and MPA, 2.5; CEE, 0.45 and MPA, 1.5; CEE, 0.3; CEE, 0.3 and MPA, 1.5; or placebo.\n Number and severity of hot flushes and Papanicolaou smear with vaginal maturation index (VMI) to assess vaginal atrophy.\n In the efficacy-evaluable population, reduction in vasomotor symptoms was similar with CEE of 0.625 mg/d and MPA of 2.5 mg/d (the most commonly prescribed doses) and all lower combination doses. CEE of 0.625 mg/d alleviated hot flushes more effectively than the lower doses of CEE alone. VMI improved in all active treatment groups.\n Lower doses of CEE plus MPA relieve vasomotor symptoms and vaginal atrophy as effectively as commonly prescribed doses.", "To compare the efficacy and endometrial safety of two estradiol valerate/dienogest combinations with Kliogest in the treatment of postmenopausal symptoms.\n This was a double-blind, randomized, multicenter study.\n Patients were randomized to estradiol valerate 2.0 mg/dienogest 2.0 mg (Climodien), estradiol valerate 2.0 mg/dienogest 3.0 mg (E2Val 2/DNG 3); or estradiol 2.0 mg/estriol 1.0 mg/norethisterone acetate 1.0 mg (Kliogest) once daily for 1 year. The primary efficacy variable was the Kupperman index. Endometrial safety was determined primarily by biopsy.\n Climodien and E2Val 2/DNG 3 were therapeutically equivalent to Kliogest (mean changes in Kupperman index -20.1, -19.0 and -18.3, respectively). No statistically significant differences existed between treatment groups in the severity of postmenopausal symptoms. The incidences of endometrial atrophy were similar in all groups. Climodien appeared to be superior to Kliogest in terms of vaginal bleeding pattern, whereas E2Val 2/DNG 3 was associated with a slightly higher incidence and greater intensity of vaginal bleeding. The incidences of adverse events were similar in all groups. A greater proportion of women in the Kliogest and E2Val 2/DNG 3 groups experienced vaginal bleeding, whereas breast problems were more common with Climodien. Climodien and E2Val 2/DNG 3 induced desirable changes in insulin-like growth factor I (decrease) and sex hormone binding globulin (increase) that were not seen with Kliogest.", "To compare bleeding control, efficacy and safety of two dose-ranging continuous combined hormone replacement therapy (HRT) regimens with those of a conventional continuous combined HRT.\n An open, 2-year, multicenter study was conducted in 393 postmenopausal women recruited from 16 study sites. The women were randomized to three continuous combined HRT regimens. One group (n = 131) started with 1 mg of estradiol valerate (E2V) plus 2.5 mg of medroxyprogesterone acetate (MPA), the second group (n = 130) received 1 mg E2V + 5 mg MPA and the third (n = 132) 2 mg estradiol (E2) and 1 mg norethisterone acetate (NETA). In the two E2V/MPA groups the initial E2V dose of 1 mg was increased to 2 mg after six cycles (one cycle = 28 days) to evaluate the effect of dose increase on bleeding control.\n The E2V/MPA regimens with a lower estrogen dose induced less bleeding and other adverse effects during the first six cycles than did the E2/NETA regimen. Bleeding disturbances and breast tenderness resulted in significantly more discontinuations in the E2/NETA group. After the estrogen dose increase in the E2V/MPA regimens, all groups showed comparable bleeding patterns and adverse effect profiles. The lower E2V dose was as effective as standard-dose E2 in relieving climacteric symptoms. All regimens provided excellent endometrial safety. No hyperplasias were reported.\n Continuous combined HRT should be started, and continued, with the lowest effective doses. An increase of the estrogen dose is recommended only if the initial dose is not sufficient for symptom control.", "A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered.", "To establish the optimum oral daily dose of micronized medroxyprogesterone acetate, given in combination with a fixed oral dose of estrone (E1) sulfate as hormone replacement therapy, that provides endometrial protection and induces cessation of vaginal bleeding.\n This multicenter, randomized, double-blind study was conducted for 2 years. Five hundred sixty-eight postmenopausal women were randomized to take E1 sulfate 1.25 mg daily and one of three doses of medroxyprogesterone acetate (2.5, 5, or 10 mg) daily. Any vaginal bleeding was recorded by patients in a daily diary, and endometrial biopsies were performed at entry into the study and at 3, 12, and 24 months.\n Forty-two percent of all women reported some bleeding at month 3 of therapy. However, by month 6, 76.5, 80.1, and 80.9% of women were amenorrheic in the 2.5-, 5-, and 10-mg medroxyprogesterone acetate groups, respectively. Over time, the percentage of women with no bleeding increased in each group, and by 24 months 91.5, 89.9, and 94.3% were amenorrheic in the 2.5- and 10-mg medroxyprogesterone acetate groups, respectively. Approximately 10% of women continue to have some bleeding, regardless of the dose of medroxyprogesterone acetate. There were no statistically significant differences in the number of women with bleeding at any time point between the three groups. There were no cases of endometrial hyperplasia reported in the study population over the 2 years.\n All three studied doses of medroxyprogesterone acetate, given in combination with 1.25 mg of E1 sulfate, provide adequate endometrial protection and render approximately 80% of women amenorrheic by 6 months of therapy.", "We sought to determine the optimum estradiol valerate-medroxyprogesterone acetate regimens for efficacy and safety.\n We performed a 24-month, randomized, double-blind phase II study. Four hundred nineteen women who were postmenopausal for at least 3 years were placed in six parallel treatment groups and received 1 or 2 mg estradiol valerate with either 2.5 or 5 mg medroxyprogesterone acetate. In two groups the dose of estradiol valerate was increased from 1 to 2 mg estradiol valerate after 6 months.\n A marked improvement of climacteric symptoms was observed, and most women had no bleeding even during the first 3 months of treatment. The best bleeding pattern was achieved with 1 mg estradiol valerate and 2.5 or 5 mg medroxyprogesterone acetate, and in most groups the bleeding pattern improved over time. No cases of hyperplasia were observed.\n All regimens alleviated climacteric symptoms and provided excellent bleeding control, even during the early weeks of treatment. A choice of various dose combinations offers flexibility of dosing, thus enabling therapy to be tailored to the needs of individual women.", "The primary objective of the Osteoporosis Prevention and Arterial effects of tiboLone study was to compare the effect of tibolone and placebo on the progression of the common carotid artery intima-medial thickness; the common carotid artery intima-medial thickness and bone data will be presented elsewhere. A secondary objective was to assess the effects of tibolone (2.5 mg), continuous combined conjugated equine estrogen/medroxyprogesterone acetate [0.625/2.5 mg], and placebo on the endometrium and vaginal bleeding; these results are the subject of this report.\n This 3-year, three-arm, international, randomized, double-blind, parallel group, placebo-controlled clinical trial enrolled 866 postmenopausal women (aged 45-79 years). The endometrium was assessed by annual transvaginal ultrasound scans and end-of-study biopsies (United States/United Kingdom centers only). Vaginal bleeding was recorded in daily diaries.\n Endometrial thickness measured by transvaginal ultrasound scan increased slightly during the first year with tibolone and conjugated equine estrogen/medroxyprogesterone acetate, without any further progression. After 3 years, there were no significant differences between the tibolone, conjugated equine estrogen/medroxyprogesterone acetate, and placebo groups in the incidence of proliferation (1.4%, 4.8%, and 0%, respectively), endometrial hyperplasia (0% in all groups), or cancer (1, 0, and 1 case, respectively). During the first 3 months, bleeding/spotting rates were greater with conjugated equine estrogen/medroxyprogesterone acetate (48%) than with tibolone (18%; P < .001) or placebo (3%; P < .001). During 3 years of treatment, the incidence of bleeding/spotting was 66%, 48%, and 23% for conjugated equine estrogen/medroxyprogesterone acetate, tibolone, and placebo, respectively. The mean number of bleeding/spotting days was greater in the conjugated equine estrogen/medroxyprogesterone acetate than the tibolone or placebo groups (61, 28, and 7 days, respectively; P = .023 vs tibolone; P < .0001 vs placebo). The mean number of bleeding/spotting episodes was also greater in the conjugated equine estrogen/medroxyprogesterone acetate group (13 episodes) compared with the tibolone group (six episodes; P < .001) and placebo group (four episodes; P < .001). Vaginal bleeding was more commonly reported as an adverse event with conjugated equine estrogen/medroxyprogesterone acetate than tibolone (26.4% vs 10.8%, P < .0001) and as the reason for premature discontinuation (9% vs 2%, P = .001).\n Compared with conjugated equine estrogen/medroxyprogesterone acetate, tibolone has a better tolerability profile with respect to vaginal bleeding but with a similar endometrial safety. These results reinforce the endometrial safety profile of tibolone.", "To assess the endometrial safety and bleeding patterns of 17 beta-estradiol sequentially combined with dydrogesterone.\n Endometrial safety and bleeding patterns were assessed in 579 postmenopausal women randomized to oral treatment with placebo, 1 mg/day 17 beta-estradiol sequentially combined with 5 or 10 mg/day dydrogesterone for the last 14 days of each 28-day cycle, or 2 mg/day 17 beta-estradiol sequentially combined with 10 or 20 mg/day dydrogesterone for the last 14 days of each 28-day cycle. Treatment was continued for 26 cycles. Proliferative endometrium, endometrial hyperplasia and endometrial malignancy in the end-of-study biopsy were considered as inadequate progestational responses.\n Biopsies were not available in 137 women mainly because of an insufficient treatment period or non-compliance. An adequate progestational response was seen in more than 98% of the 442 women who underwent biopsy after treatment. Bleeding data were not available in 193 women, most of whom did not remain on treatment for the full 26 cycles. The 1-mg 17 beta-estradiol dose was associated with less cyclic and intermittent bleeding than the 2-mg dose. Higher doses of dydrogesterone were associated with a higher incidence of cyclic bleeds and a later day of onset, while duration, severity and regularity were similar in all groups irrespective of estradiol or dydrogesterone dose.\n Sequential combinations of 1 mg 17 beta-estradiol with 5 or 10 mg dydrogesterone and 2 mg 17 beta-estradiol with 10 or 20 mg dydrogesterone are associated with very good endometrial safety. The incidence of bleeding is lower with the 1-mg dose of 17 beta-estradiol.", "To investigate the difference in histopathology and cell cycle kinetics in the menopausal endometrium treated with sequential-combined hormone replacement therapy (HRT) using different types and doses of progestins.\n A randomized, double-blind, 1-year study was conducted. In a menopause clinic of a university hospital, 241 postmenopausal women using HRT were included for the study of histopathology and cell cycle analysis. Conjugated equine estrogens, 0.625mg/day, were administered for 25 days (days 1-25) of each month, and the following were also administered for 14 days (days 12-25): in group A ( n= 102), medroxyprogesterone acetate (MPA), 5 mg/day; in group B ( n= 66), MPA, 10mg/day; and in group C ( n= 73), dydrogesterone, 20mg/day. Endometrial sampling was performed after at least 10 months of treatment. Fifty-two premenopausal women were also enrolled for the comparative studies (group Y). The S-G2-M fractions in the cell cycle were used as the marker of proliferation.\n Most menopausal endometria were normal regardless of the regimens of HRT. Endometrial hyperplasia was only found in two cases (both in group A). The S-G2-M fractions of the endometrial cells in all three menopausal groups showed no statistically significant difference. It appeared that S-G2-M fractions increased from normal postmenopausal to normal premenopausal endometria to postmenopausal hyperplasia to premenopausal hyperplasia. The S-G2-M fractions of the normal menopausal endometrial cells were lower than those of the premenopausal controls either in normal or in hyperplastic categories.\n Our study showed that there is no difference between the effect of MPA and dydrogesterone used in sequential-combined HRT based on the cycle kinetics of the menopausal endometrium.", "Postmenopausal women taking oestradiol 17-beta 2 mg daily were randomized to receive either 25 or 50 microg gestodene from day 17 to 28 of the cycle in a double-blind study. Placental protein P14 (PP14) and CA 125 concentrations in uterine flushing, endometrial morphology and irregular bleeding after 12 cycles of study were observed. Eleven and 12 women in the 25 and 50 microg groups respectively completed the study. There were no significant differences in pre-treatment biochemical and morphological indices between the groups. The median PP14 concentration increased from 332 to 5800 ng/ml (P < 0.001) and from 145 to 27 160 ng/ml (P < 0.001) in the 25 and 50 microg gestodene groups respectively. No between-group significant rise of PP14 was observed. Similarly, no significant change was seen between the initial and post-treatment concentrations of CA 125 for either group. All biopsies were atrophic at inception of the study, and both regimens produced secretory endometrial transformation in the majority of biopsies. No between-group difference was observed in the morphometric indices measured, or any significant correlation between the concentrations of PP14 or CA 125 and morphology. The mean number of days of withdrawal bleeding (3.8 and 4.2 days for 25 and 50 microg respectively) were similar. In conclusion, both regimens produced a significant rise in uterine flushing concentrations of PP14, but not CA 125. PP14 is a sensitive biochemical marker in the assessment of endometrial response to hormone replacement therapy.", "Healthy postmenopausal women were randomly assigned to groups receiving 28-day treatment cycles of estradiol (E2) valerate (2 mg, days 1-21) combined with medroxyprogesterone acetate (10 mg, days 12-21) (N = 18), 17 beta-estradiol (1.5 mg, days 1-24) combined with desogestrel (150 micrograms, days 13-24) (N = 20), or placebo (N = 18). The progestational effects on the endometrium were assessed by histology, uterine bleeding pattern, and biochemical markers of secretion measured in endometrial tissue (E2 and isocitrate dehydrogenase) and serum (placental protein 14). After 2 years of therapy, 24 women in the hormone groups had secretory endometrium and 13 had atrophic endometrium; in the placebo group, the results were one and 15, respectively. Withdrawal bleeding generally started between days 9-12 after the addition of progestogen in the E2-medroxyprogesterone acetate group, and between days 14-17 in the E2-desogestrel group. All three biochemical markers of secretion were increased in each of the hormone-treated groups compared with the placebo group (P less than .01-.001). Serum placental protein 14 was twice as high in the secretory as in the atrophic phase (P less than .01). Isocitrate dehydrogenase, but not E2 dehydrogenase, was also higher in the secretory phase (P less than .05). Only serum placental protein 14 was significantly related to the uterine bleeding pattern (P less than .01). We conclude that serum placental protein 14 reflects both endometrial histology and bleeding pattern and may be a useful marker of progestational effects on the endometrium. The markers of secretion measured in endometrial tissue are not as reliable for endometrial histology or bleeding pattern.", "To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis.\n A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily.\n BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo).\n The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.", "The aim of the study was to assess the dose-response effects on the postmenopausal endometrium of 3 sequential combined hormone replacement regimens and 1 continuous combined hormone replacement regimen of estradiol and gestodene. Study Design: In this 2-year double-blind, placebo-controlled study, 278 healthy postmenopausal women received either 2 mg estradiol sequentially combined with 50 microg or 25 microg gestodene, 1 mg estradiol sequentially or continuously combined with 25 microg gestodene, or placebo.\n All 4 hormone treatment regimens produced a safe endometrial histologic appearance. The regimens that were based on the lower dose of 1 mg estradiol was associated with less uterine bleeding than were those that were based on 2 mg estradiol. For sequentially opposing the 2 mg dose of estradiol, the dose of 25 microg gestodene was less efficient in producing secretory activity than was the dose of 50 microg gestodene. The measurement of placental protein 14 in serum reflected the secretory transformation of the endometrial buildup.\n The reduction in bleeding episodes associated with regimens with lower estradiol doses may lead to improved long-term therapy compliance by menopausal women. The potency of progestogens can be assessed by measuring the serum concentration of placental protein 14.", "To evaluate low doses of 17 beta-estradiol (E2) and norethisterone acetate (NETA) as continuous combined hormone replacement therapy (HRT) in their effects on vasomotor symptoms, bleeding episodes, endometrial histology and mastalgia.\n Sixty postmenopausal women were randomly allocated to three treatment groups and were given 1 mg E2 and 0.25 mg NETA (A), 1 mg E2 and 0.5 mg NETA (B) and 2 mg E2 and 1.0 mg NETA (C) in daily doses. The treatment period was 1 year.\n A similar statistically significant reduction of climacteric symptoms (P < 0.05) was found in all groups. Bleedings, mainly as spottings, occurred most commonly during the first treatment months. Fewer bleeding episodes and a higher percentage of amenorrhea was noted in group B compared to the other groups but did not reach statistical significance. All endometrial biopsies showed atrophy. Women in group A and B had less severe mastalgia (P < 0.05) compared to group C, given higher doses of steroids.\n Postmenopausal women taking 1 mg of E2 plus 0.5 mg NETA as continuous combined HRT reported a marked reduction of climacteric complaints and good bleeding control. No endometrial proliferation was detected after 1 year of treatment. This type of therapy may be beneficial especially for elderly women, in whom bleeding may be annoying.", "This randomized, double-blind, multicenter study was planned to compare the efficacy and tolerance of a novel oral regimen containing estradiol (2.0 mg) sequentially combined with trimegestone, at a daily dose of either 0.25 mg or 0.5 mg, with a standard hormone replacement therapy containing estradiol and norethisterone acetate (E2 + NETA) in the treatment of climacteric symptoms.\n The study was conducted over 13 cycles, each of 28 days, and involved 487 subjects, of whom 349 completed the study.\n All three treatments were equally effective in alleviating hot flushes and showed a progressive and significant reduction in the value of the Kupperman index. The treatments diminished equally effectively urogenital signs and symptoms. All treatments were well tolerated and the incidences of adverse events associated with each treatment were similar across the treatment groups. The duration of expected withdrawal bleeding was shorter in the estradiol + trimegestone 0.5 mg group than in the estradiol + trimegestone 0.25 mg or E2 + NETA group.\n All treatments were effective and well tolerated, providing significant relief from climacteric symptoms. Treatment with estradiol + trimegestone 0.5 mg provided the most favorable bleeding pattern.", "To report the histological findings of the endometrium of postmenopausal women who were randomized to receive placebo, estrogen only, or one of three estrogen plus progestin (E+P) regimens in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.\n A 3-year multicenter, randomized, double-masked, placebo-controlled trial.\n A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy.\n Participants were randomized and stratified in equal numbers to one of the following treatments in 28-day cycles: placebo, 0.625 mg/d of conjugated equine estrogens (CEE), 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate (MPA) for the first 12 days, 0.625 mg/d of CEE plus 2.5 mg/d of MPA, or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone (MP) for the first 12 days.\n Histology of endometrium collected at baseline, annual, or unscheduled visits by biopsy, curettage, or hysterectomy.\n Intention to treat.\n During follow-up women assigned to estrogen alone were more likely to develop simple (cystic), complex (adenomatous), or atypical hyperplasia than those given placebo (27.7% vs 0.8%, 22.7% vs 0.8%, and 11.8% vs 0%, respectively) for the same types of hyperplasia (P < .001). Participants administered one of the three E+P regimens had similar rates of hyperplasia as those given placebo (P = .16). The occurrence of hyperplasia was distributed evenly across the 3 years of the trial. Women taking estrogens alone also had more unscheduled biopsies (66.4% vs 8.4%; P < .001) and curettages (17.6% vs 0.8%; P < .001) than women receiving placebo. The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens (P = .38). Of the 45 women with complex (adenomatous) or atypical hyperplasia, study medications were discontinued in all, and the biopsy results of 34 (94%) of 36 women with hyperplasia reverted to normal with progestin therapy. The remainder had dilatation and curettage (n = 2) or hysterectomy with (n = 2) or without (n = 6) prior medical therapy, or refused further biopsies (n = 1). One woman developed adenocarcinoma of the endometrium while receiving placebo.\n At a dosage of 0.625 mg, the daily administration of CEE enhanced the development of endometrial hyperplasia. Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only therapy.", "In this prospective, double-blind study, we evaluated the efficacy and safety of low-dose estrogen and progestin replacement therapy in 36 postmenopausal women who were administered oral medroxyprogesterone acetate (MPA) cyclically or continuously in combination with conjugated equine estrogen (CEE) 0.625 mg daily. In the sequential group, MPA (5.0 mg) was administered daily for 12 days of each 25-day treatment cycle. In the two continuous groups, MPA was administered without interruption at a daily dose of either 2.5 mg or 5.0 mg for 12 treatment cycles. Of the 36 women in the study, 29 women completed the one-year protocol. The clinical and metabolic responses were assessed before and every three cycles during the 12 cycles of treatment. Endometrial biopsies and lumbar bone density scans were performed before and during the last week of the 12th treatment cycle. Vasomotor and urogenital symptoms improved in all women. Cyclic menstrual bleeding occurred in all patients on sequential therapy, and proliferative endometrium was noted in two of these women. All patients in both continuous treatment groups experienced amenorrhea after the fifth cycle of therapy, and all endometrial biopsies were atrophic or inactive. From the 3rd through the 12th month of cycle, favorable lipid and lipoprotein changes occurred in all treatment groups. Lumbar bone mineral density improved significantly (P < .05) by an average of 6.41% in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effects of cyclical treatment with estrone sulfate (0.3, 0.625, or 1.25 mg), plus calcium carbonate, on spinal trabecular bone density were compared with placebo in 120 postmenopausal women in this 2-year, multicenter, double-blind study. While the placebo and 0.3-mg treatment groups lost bone density (-3.6% and -5.1%), the 0.625- and 1.25-mg treatment groups experienced no significant change from baseline at 24 months (-0.8% and +0.7%). The 1.25-mg treatment group was significantly different from the placebo group at 12, 18, and 24 months. Although the 0.625-mg treatment group was significantly different from the placebo group only at 18 months, the data suggest that 0.625 and 1.25 mg of estrone sulfate had different effects than placebo and 0.3 mg of estrone sulfate and, given with supplemental calcium, are effective doses for the prevention of spinal bone loss.", "The purpose of this study was to determine the incidence of endometrial hyperplasia in subjects who receive continuous norethindrone acetate and ethinyl estradiol combinations versus unopposed ethinyl estradiol.\n Nine hundred forty-five postmenopausal women were randomly selected for 12 months of treatment with one of six blinded norethindrone acetate/ethinyl estradiol combinations (milligrams of norethindrone acetate/micrograms of ethinyl estradiol: 0/5, 0.25/5, 1/5, 0/10, 0.5/10, or 1/10) or to open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate. Endometrial hyperplasia and endometrial proliferation were assessed by biopsy at screening, months 6 and 12.\n Endometrial hyperplasia developed in 26 subjects: Placebo, 0/5 and 0.25/5 (1 subject each) and 0/10 (23 subjects). Significantly less endometrial proliferation was measured in the 1/5 norethindrone acetate/ethinyl estradiol and other norethindrone acetate/ethinyl estradiol combination groups and in the 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate group, than in unopposed ethinyl estradiol groups (6 months: P <.004; 12 months: P <.001). Treatment with 1/5 norethindrone acetate/ethinyl estradiol and with other norethindrone acetate/ethinyl estradiol combinations significantly reduced endometrial proliferation compared with 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (6 and 12 months: P <.02).\n Norethindrone acetate protects the endometrium from estrogen-induced hyperplasia and changes in proliferative status. In addition, norethindrone acetate/ethinyl estradiol-treated subjects had significantly less endometrial proliferation compared with 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate-treated subjects.", "This pilot study was conducted to establish the optimum oral dosage of medroxyprogesterone acetate (Provera) given daily in combination with a fixed dose of piperazine oestrone sulphate (Ogen), as hormone replacement therapy. A group of 32 nonhysterectomized, symptomatic menopausal women were randomly allocated to receive piperazine oestrone sulphate 1.25 mg daily and medroxyprogesterone acetate 2.5 mg, 5 mg or 10 mg daily for a 2-year period. This was an open study and the patients were reviewed at 3-monthly intervals for 2 years. Vaginal bleeding was reported by 58% of patients after the first 3 months of treatment. There was a gradual decline in the reported incidence of bleeding over the following 6 months particularly by women in the 5 mg and 10 mg Provera group. Only 10% of patients were still recording slight bleeding in the 10 mg group at 12 months. By 24 months all the women in the 5 mg and 10 mg Provera groups had ceased bleeding. There were 2 patients in the 2.5 mg Provera group with persistent proliferative endometrium at 24 months. All the remaining patients had atrophic endometrium. There was no significant difference in serum lipid changes between the 3 groups, but there was an overall reduction in total cholesterol, triglycerides and low density lipoprotein cholesterol in all women. There was no significant difference in bone mineral density changes between the groups over the 2-year period. Endometrial protection with increased incidence of amenorrhoea, without significant adverse effects, was seen with the use of 5 mg and 10 mg of provera.", "To investigate the effects of two dosages of conjugated equine estrogen (CEE) in preventing bone loss in early postmenopausal women.\n Two hundreds and thirty six early postmenopausal women were randomly given one of the following regimens for two years. Groups A (GA): CEE 0.625 mg + medroxyprogesterone (MPA domestic made) 2 mg + caltrate-D (Ca-D) 1 tablet daily; Group B (GB): CEE 0.3 mg + MPA 2 mg + Ca-D 1 tablet daily; Group C (GC): Ca-D 1 tablet daily alone. The observation endpoints included: (1) bone mineral density (BMD) of lumbar 2 - 4 (L(2 - 4)) measured by duel energy X-ray absorptiometry (DEXA, Lunar DPX-L) before and 1, 2 years after treatment; (2) vaginal bleeding recorded daily and endometrium thickness yearly by transvaginal ultrasonography. Endometrium biopsies were performed if its thickness greater than 5 mm.\n Two hundreds and thirteen (90%) cases completed 1-year study, 176 (75%) 2 year study. In GA L(2 - 4) BMD significantly increased both after 1 and 2 year treatment as compared with pretreatment value (P < 0.001). While in GB, L(2 - 4) BMD significantly elevated only after 1 year treatment, but did not reach significance during the end of 2 year therapy. In contrast, L(2 - 4) BMD decreased by 0.4% and 1.6% respectively after 1, 2 year of GC although without significance. Compared among the three group, the increments of mean L(2 - 4) BMD after 1 year treatment in GA and GB were significantly different from, that in GC (+2.3%, +2.7% versus -0.4%, P < 0.001, P < 0.05 respectively). So were the values after 2 year treatment (+3.7%, +0.7% versus -1.6%, P < 0.001, P < 0.05 respectively). As compared the mean L(2 - 4) BMD between GA and GB, the difference reached significance only after 2 year (P < 0.01), but not after 1 year treatment (P > 0.05). The vaginal bleeding rate in GA during the first month and 1, 2 year after treatment were higher than those in GB and GC (52% versus 16%, 9%; 43% versus 12%, 2.8%; 34% versus 8%, 3.3%). Endometrium biopsies were carried in 153 cases (27 had endometrium thicker than 5 mm) in GA and GB. No atypical hyperplasia was found, but 2 cases showed simple hyperplasia in the GA. One case in GA developed superficial thromphlebitis during the 1 year treatment.\n Both 0.625 mg and 0.3 mg daily of CEE continuously combined with domestic MPA are effective in preventing postmenopausal osteoporosis. The former has more stronger effect than the latter, but needs higher dose of MPA when combined continuously in order to decrease the vaginal bleeding rate and preventing endometrium hyperplasia.", "Treatment with unopposed estrogen is known to increase the risk of endometrial hyperplasia, atypia, and carcinoma, and therefore the administration of a progestin during hormone replacement therapy (HRT) is recommended. The addition of a progestin may cause unwanted side effects. Progestin administration of various durations are therefore used in HRT.\n Data were obtained about endometrial histopathology, bleeding interval and compliance in 240 early postmenopausal women receiving HRT with a progestin administered for 10 days during 12 week or 4 week cycles of estrogen administration. These regimens were studied for as long as 4 years. The daily estrogen given was 17beta-estradiol 2 mg per day which was reduced to 1 mg day during the last 6 days of each cycle. The progestin used was norethindrone acetate, given at a dose of 1 mg per day.\n The incidence of endometrial hyperplastic changes, i.e. simple or complex hyperplasia, atypia or cancer, was significantly higher in the 12 weeks cycle than in the monthly cycle group (P = 0.003), with an overall annual incidence of 5.6% in the 12 weeks cycle group and 1% in the monthly cycle group. One case of atypical hyperplasia and one case of endometrial adenocarcinoma was observed in the long cycle group. Long cycle treatment produced more irregular bleeding pattern. Accordingly, the rate of drop-out due to bleeding was significantly higher in the long cycle group (P<0.01).\n We conclude that the long cycle HRT modality investigated did not improve compliance and may increase the risk of endometrial hyperplasia and eventually cancer compared to conventional HRT with a monthly cycle. Caution using long cycle HRT regimens is advisable, and careful monitoring of the endometrium during treatment is recommended.", "To compare the efficacy and tolerability of a novel oral constant estrogen plus intermittent progestogen hormone replacement therapy (HRT) regimen to a continuous combined HRT regimen in postmenopausal women.\n Subjects were randomly assigned to receive treatment with either constant 17beta-estradiol (E2), 1 mg, plus intermittent norgestimate (NGM) 90 microg (3 days off, 3 days on) (n=221) or E2 2 mg/norethisterone acetate (NETA) 1 mg (n=217) for 1 year. Treatments were evaluated based on the incidence of hot flushes and uterine bleeding.\n Both regimens had similar bleeding profiles and provided comparable vasomotor symptom relief. However, breast discomfort and edema were experienced by twice as many subjects who received E2/NETA.\n The constant E2/intermittent NGM regimen was well tolerated and possesses similar efficacy compared with a continuous combined E2/NETA regimen and may be considered whenever HRT without withdrawal bleeding is deemed appropriate.", "To evaluate the effect of 1- or 3-monthly sequential combinations of estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) on menopausal symptoms, bone density, muscle strength and lipid metabolism in postmenopausal women.\n Changes in bone mineral density (BMD), isometric muscle strength, serum lipids and climacteric symptoms were evaluated in 78 women, 49-55 years of age, with a spontaneous menopause 0.5-3 years earlier. Treatment group I received 2 mg E2V tablets for 11 days, followed by 2 mg E2V + 10 mg MPA for 10 days and placebo for an additional 7 days; treatment group II received 2 mg E2V for 70 days, 2 mg E2V + 20 mg MPA for 14 days, and placebo for 7 days. The placebo group received placebo continuously for 24 months. Each group was further randomised to exercise and non-exercise subgroups.\n Both hormone regimens significantly reduced menopausal symptoms, and prevented equally well the decrease of BMD both in the lumbar spine and proximal femur. A positive effect of exercise on BMD was observed in the placebo group. No synergistic effect of exercise and estrogen on BMD could be shown. Both hormone regimens increased the isometric strength of back extensor muscles. Serum total and LDL cholesterol decreased during the first year with both estrogen regimens.\n Estrogen-progestin regimens were equally effective in the control of menopausal symptoms and preventing bone loss, increasing muscle strength and lowering serum cholesterol.", "This double-blind, randomized, multi-center study compared the efficacy and clinical tolerance of a combined formulation containing 2 mg estradiol (E2) and 0.5 mg trimegestone (TMG) with a standard hormone replacement therapy containing estradiol valerate (E2V) and norgestrel (NG) in the treatment of climacteric symptoms. The study was conducted over 13 cycles, each of 28 days, and involved 634 subjects, of whom 481 completed the study. The primary efficacy variable was the percentage of subjects who showed at least a 50% reduction from baseline in the mean daily number of hot flushes in cycle 3. This was observed in 98.5% of the subjects in the E2 + TMG group and 93.3% of the subjects in the E2V + NG group (95% confidence interval of the difference, -8.6, -1.9). Significant differences in favor of the E2 + TMG combination were observed in the reduction in the mean daily number and severity of hot flushes, and in the percentage of subjects who had hot flushes at baseline but no hot flushes during treatment. There were no significant differences between the treatments in the Kupperman index and in urogenital signs or symptoms. Treatment with the E2 + TMG combination was well tolerated and the incidences of adverse events were similar in the two treatment groups. Breast pain was the main adverse event, possibly related to treatment that resulted in discontinuation. The mean number of bleeding days per cycle was significantly lower with the E2 + TMG combination than with the E2V + NG combination. The incidences of endometrial hyperplasia were low and comparable in both treatment groups. It was concluded that the E2 + TMG combination was either equivalent or superior to the E2V + NG combination in the treatment of hot flushes and other climacteric symptoms, and that its bleeding profile was favorable.", "To study progestin administration at less than monthly intervals in postmenopausal women given continuous estrogen replacement.\n Eighty postmenopausal women received 0.625 mg/day of conjugated equine estrogens for 48 weeks. Using a double-masked design, the subjects were randomized to medroxyprogesterone acetate 10 mg/day for 14 days every 28 or 84 days, or the same dosage for 28 of 84 days. Bleeding patterns, endometrial histology, and serum lipids were assessed.\n The total days of bleeding during the 48-week study were significantly reduced (P < .05) in the women given the progestin for 14 days every 3 months (mean +/- standard deviation 29 +/- 16 days) than with the other two regimens. In all groups, secretory endometrium was reported in 17-39%. At 24 but not 48 weeks, simple hyperplasia was observed in one subject in each of the less than monthly progestin groups. Significant increases (P < .05) of high-density lipoprotein cholesterol were observed before but not after medroxyprogesterone acetate in the women receiving it less than monthly. No change was seen with monthly progestin.\n In this direct comparison, medroxyprogesterone acetate given for 14 days every 3 months elicited less vaginal bleeding than standard monthly administration. Only a single woman had simple hyperplasia with each regimen of progestin given every 84 days. Medroxyprogesterone acetate given for 14 days every 3 months represents a possible alternative to standard monthly therapy if coupled with regular assessment of the endometrium.", "Estrogen therapy is known to prevent osteoporosis, but studies have shown that conventional doses increase adverse events. Whether lower doses, one quarter of standard treatment, prevent bone loss is not known.\n To examine the effect of 3 years of treatment with 0.25 mg/d of micronized 17beta-estradiol on bone mineral density (BMD) and bone turnover in healthy older postmenopausal women.\n Randomized, double-blind, placebo-controlled trial conducted from July 24, 1998, through June 14, 2002, at a university general clinical research center in the United States. Healthy, community-dwelling women (N = 167) who were older than 65 years at enrollment.\n Dosage of 0.25 mg/d of micronized 17beta-estradiol (n = 83) or placebo (n = 84); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months.\n The BMD of the hip, spine, wrist, and total body measured annually for 3 years. Serum and urine biochemical markers of bone resorption and formation and sex hormones were measured at baseline, 3 months, and during years 1 and 3 of treatment.\n Mean BMD increased at all sites for participants taking low-dose estrogen (17beta-estradiol) compared with placebo (P<.001). Compared with participants receiving placebo, participants taking low-dose estrogen had BMD increases of 2.6% for the femoral neck; 3.6%, total hip; 2.8%, spine; and 1.2%, total body. Markers of bone turnover, N-telopeptides of type 1 collagen, and bone alkaline phosphatase decreased significantly (P<.001) in participants taking low-dose estrogen compared with placebo. Estradiol, estrone, and sex hormone-binding globulin levels increased in the estrogen-treated group compared with placebo. The adverse effect profile was similar; specifically, there were no statistically significant differences in breast tenderness, changes in endometrial thickness or pathological effects, or annual mammographic results between the 2 groups. The number of abnormal mammograms over 3 years was 15 for the low-dose estrogen group and 10 for the placebo group (8 occurred at baseline) (P =.26). There were no reports of breast cancer during the study.\n In older women, a dosage of 0.25 mg/d of 17beta-estradiol increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects. Future studies evaluating the effect of low-dose estrogen on fractures are indicated.", "Two randomized comparative multicenter studies were conducted to establish the endometrial safety and tolerability of a triphasic sequential hormone replacement estradiol valerate/medroxyprogesterone acetate (E2V/MPA) therapy regimen.\n Study 1 was a randomized, double-blind, clinical phase III study in 399 postmenopausal women, following parallel-group design with two groups. The duration of study treatment was 12 or 13 cycles of 28 days. A double-dummy technique was used to ensure blinding in the study. The investigational drugs were E2V/MPA triphasic and E2V/MPA biphasic (Diviseq and Divina, respectively; Orion Pharma). In study 2, a total of 341 subjects were randomly allocated by computer into two parallel groups receiving either E2V/MPA or estradiol/norethisterone acetate triphasic (E2/NETA, Trisequens; Novo Nordisk A/S) for 12-13 cycles. The study was an open, clinical phase III trial with a randomized, parallel-group design. Endometrial biopsies combined with transvaginal ultrasound were undertaken before and at the end of treatment during the progestogen phase. Bleeding patterns and symptom control were assessed throughout both studies.\n E2V/MPA triphasic was found to have similar endometrial effects and bleeding patterns to those with E2V/MPA biphasic and E2/NETA triphasic. Climacteric symptoms were relieved as quickly and effectively as with the two comparator treatments. No adverse drug reactions specific to E2V/MPA triphasic were observed. At the end of the study, the proportions of secretory samples were 67.1% for the combined E2V/MPA triphasic groups, 65.6% for the E2V/MPA biphasic group and 71.6% for the E2/NETA triphasic group. One case of hyperplasia occurred in the E2V/MPA triphasic group. Thus the incidence of hyperplasia for the combined groups was 0.33%.\n The triphasic E2V/MPA regimen was well tolerated and produced endometrial effects similar to those of the two comparators. Extending estrogen during the so-called treatment-free week with a lower dose of estradiol was effective in controlling vasomotor symptoms.", "We evaluated four oral combinations of conjugated estrogens (Premarin) and medroxyprogesterone acetate in preventing endometrial hyperplasia, which can occur with conjugated estrogens alone.\n This was a 1-year prospective, double-blind, randomized, multicenter study in 1724 postmenopausal women. All five groups took conjugated estrogens (0.625 mg) daily. The respective medroxyprogesterone acetate dosages were 2.5 and 5.0 mg daily (groups A and B) and 5.0 and 10.0 mg for 14 days per 28-day cycle (groups C and D).\n Among the 1385 patients with valid biopsy data, endometrial hyperplasia developed in 20% in the conjugated estrogens-treated group and < or = 1% in each of the four conjugated estrogens/medroxyprogesterone acetate-treated groups. The incidence of endometrial hyperplasia did not differ significantly between any of the conjugated estrogens/medroxyprogesterone acetate regimens. However, none of the patients receiving the two higher medroxyprogesterone acetate dosages (groups B and D) had endometrial hyperplasia.\n The endometrial hyperplasia incidence was significantly lower in women treated with conjugated estrogens and medroxyprogesterone acetate than in women treated with conjugated estrogens alone.", "We compared two different continuous combined hormone replacement therapy (HRT) regimens of estradiol valerate (E(2)V) and medroxyprogesterone acetate (MPA) with a combination of micronized estradiol (E(2)) and norethisterone acetate (NETA) to determine bleeding pattern, control of climacteric symptoms, lipid profile, endometrial and general safety in a 1-year multicenter study.\n 440 postmenopausal women were randomized to three treatment groups to receive: 1 mg E(2)V+2.5 mg MPA; 1 mg E(2)V+5 mg MPA; or 2 mg of E(2)+1 mg NETA. After the first 6 months, the E(2)V dose was increased to 2 mg in both E(2)V/MPA groups. Information on bleeding was recorded on diaries by the women and intensity of climacteric symptoms was assessed using VAS scales. Physical and laboratory examinations, endometrial biopsy and vaginal ultrasonography were performed at baseline and follow-up visits.\n Significantly fewer bleeding days were experienced in the first 3 months by women taking E(2)V/MPA compared with women taking E(2)/NETA. When the dose of E(2)V was increased in the E(2)V/MPA groups, an increase in maximum bleeding intensity was observed in the group receiving 2.5 mg of MPA, but not in the group taking 5 mg of MPA. All dose combinations effectively relieved climacteric symptoms and beneficial effects on the lipid profile were seen after 6 months in all groups. Tolerability and endometrial safety were good and no cases of hyperplasia were observed. More women discontinued treatment prematurely in the E(2)/NETA group compared with either of the E(2)V/MPA groups. The overall continuation rates ranged from 70 to 86%.\n These results confirm that lower dose combinations of continuous combined HRT are usually sufficient to control symptoms or avoid breakthrough bleeding. However, if higher E(2)V dose is needed for symptom control, it should be combined with the higher dose of progestin (5 mg) to avoid bleeding disturbances. Flexible treatment regimens should be available for individualized HRT.", "The purpose of this multicenter, double-blind, randomized, parallel-group study was to determine the effect of thirteen 28-day cycles of drospirenone combined with estradiol, compared with estradiol alone, on the endometrium of postmenopausal women.\n Postmenopausal women not on hormone therapy but with an intact uterus were enrolled (N = 1,147); 1,142 were evaluated. Participants were randomly assigned to treatment with 1.0 mg of estradiol alone (E(2) monotherapy) or 1.0 mg of estradiol plus 0.5, 1.0, 2.0, or 3.0 mg of drospirenone (DRSP/E(2)). Endometrial biopsies were performed at baseline, at 7 months if indicated, and at study end in the 13th month. Safety was evaluated with peripheral blood samples for hematology, liver and renal function, and lipids, along with vital signs and interval medical evaluations.\n When compared with estradiol alone, combinations of drospirenone and estradiol were effective in protecting against endometrial hyperplasia. The probability of hyperplasia was 0.060 (95% CI, 0.043-0.078) for the E(2) monotherapy group, 0.007 for the 2-mg DRSP/E(2) group, and nonsignificant for the remaining drospirenone/estradiol groups. Endometrial bleeding decreased in all treatment groups over time. The combination of drospirenone and E(2) relieved menopausal symptoms and resulted in improvements in health-related quality-of-life measures. There were no significant adverse events, and effects on triglycerides, total cholesterol, and high-density lipoprotein cholesterol were positive.\n The use of drospirenone combined with estradiol provides protection against endometrial hyperplasia, reduces endometrial bleeding with time, and relieves menopausal symptoms. There were no safety issues and blood pressure was reduced in women with hypertension.", "To determine bleeding patterns and endometrial response in postmenopausal women taking low-dose (1 mg) estradiol in a sequential combined formulation with 5 or 10 mg dydrogesterone.\n A total of 151 postmenopausal women were allocated randomly to 5 or 10 mg dydrogesterone during cycle days 15-28 in a sequential oral formulation with 1 mg estradiol continuously during 13 cycles of 28 days. Occurrence of vaginal bleeding was recorded daily and analyzed in accordance with World Health Organization (WHO) standards. Endometrial biopsies, obtained at baseline and cycle days 25-27 of the final treatment cycle, were interpreted independently by two pathologists.\n The study was completed by 131 women (87%). The percentage of women with bleeding (mean +/- SD) was 57.2 +/- 3.6% in the 1/5-mg group and 65.8 +/- 4.2% in the 1/10-mg group (p < 0.001); cross-sectional analysis showed that, in every cycle, there were more women with bleeding in the 1/10-than in the 1/5-mg group (p < 0.001). With regard to the day of onset of bleeding, the mean difference between groups was 1.4 +/- 1.1 days (p < 0.001). There was no difference in duration of bleed (5 days), or intensity or incidence of intermittent bleeding (3-14% per cycle). Both regimens resulted in high rates of amenorrhea in each cycle (26-49%), but only 14/151 (9%) women were amenorrheic throughout. Three patients (2%) discontinued owing to bleeding problems. Endometrial protection was adequate in 98.3% (1/5-mg group) and 98.5% (1/10-mg group) with only one case of proliferation (1/10-mg group) and one of simple hyperplasia (1/5-mg group).\n The bleeding pattern associated with low-dose (1 mg) estradiol sequentially combined with 5 or 10 mg dydrogesterone shows a high rate of amenorrhea in each cycle; there is a dydrogesterone dose effect on the occurrence and day of onset of bleeding. Bleeding episodes that occur show a regular pattern and are of slight intensity. The endometrial safety of both regimens is high.", "The endometrial response to oral, cyclic conjugated equine estrogens with and without the randomized addition of medroxyprogesterone acetate was evaluated in 95 postmenopausal women with respect to morphology and bleeding patterns. At 1 year, therapy with 0.625 mg conjugated equine estrogens or 1.25 mg conjugated equine estrogens for 25 days of a 30-day cycle and 5 mg medroxyprogesterone acetate added to the last 11 days of the conjugated equine estrogens cycle was associated with hyperplasia in 0 and 10% of the patients, respectively (P = not significant). Hyperplasia developed in 30 and 57% of the patients who received the above conjugated equine estrogens and placebo regimens, respectively. Irregular, breakthrough bleeding occurred in 14% of the conjugated equine estrogens/medroxyprogesterone acetate users and in 54% of the conjugated equine estrogens/placebo users. The results of this study indicate that 1 year of therapy with 0.625 mg conjugated equine estrogens and 5 mg medroxyprogesterone acetate provided the most satisfactory endometrial protection against hyperplasia and was associated with relatively low rates of breakthrough bleeding.", "To compare the bleeding profiles and endometrial protection of two sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a sequential estradiol valerate (E2V)/norethisterone (NET) regimen.\n This was a randomized, double-blind, multicenter study conducted in eight countries in healthy, postmenopausal women with an intact uterus. A total of 1218 women were enrolled into the initial 1-year study (13 cycles), and subsequently 531 of these received treatment for a further year (26 cycles). Treatment regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg 17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg NET on days 17-28.\n Mean percentage of women reporting onset of withdrawal bleeding episodes during the week following discontinuation of progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other two treatments, showing a more efficient progestogen effect on the endometrium and good predictability of bleeding onset with this treatment. The mean numbers and average lengths of bleeding episodes were similar in the three treatment groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25 mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens demonstrated a good protective effect on endometrial proliferation, with the 0.25 mg TMG dose showing a lower incidence of proliferative endometrium.\n The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the endometrium, with an overall favorable bleeding profile.", "To compare the effects of frequently used two different regimens of combined continuous hormone replacement therapy; 0.625 mg conjugated equine estrogen (CEE) + 2.5 mg medroxyprogesterone acetate (MPA) and 1 mg 17beta estradiol (E2) + 0.5 mg norethindrone acetate (NETA), on endometrial histopathology and postmenopausal uterine bleeding.\n Two hundred and forty-six outpatient subjects aged 41-57 years were enrolled in the study conducted at the menopause clinic between November 2003 and November 2004. One hundred and thirty-nine patients were assigned to receive 0.625 mg conjugated equine estrogen + 2.5 mg medroxyprogesterone acetate (CEE/MPA), whereas 107 patients were to receive 17beta estradiol + 0.5 mg norethindrone acetate (E2/NETA). Inclusion criteria of the study were: normal values of endometrial thickness at basal evaluation, women with intact uterus, at least 12 months of amenorrhea, normal vaginal smear, bilateral mammography and biochemical blood parameters. All women were questioned every 3 months for vaginal bleeding/spotting. Endometrial sampling was performed by Pipelle catheter in the 12th month of therapy.\n For the first 3 months, vaginal bleeding/spotting rate for the CEE/MPA group was 38.7%, whereas it was higher (45%) in the E2/NETA group. For the second 3-month period, vaginal bleeding/spotting frequencies were 41.1 and 37.8%, respectively. In the third 3-month period 30.6 and 29.6%, and in the fourth 3-month period, 18.5 and 12.5% of the patients reported vaginal bleeding or spotting. None of the results of endometrial sampling have shown findings of cancer histopathology.\n Compared to CEE/MPA regimen, E2/NETA therapy has not shown more favorable effects on postmenopausal bleeding abnormalities. Irregular endometrial proliferation was seen more with the E2/NETA regimen.", "With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.", "Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain.\n To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States.\n Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.\n Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).\n The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.\n On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.\n Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD." ]

[ "3776752" ]

[ "The management of urinary incontinence in local authority residential homes for the elderly." ]

[ "Urinary incontinence occurring at least once weekly was found in 32% of residents in 30 Local Authority Residential Homes for the Elderly. Incontinence was significantly commoner among female residents. One hundred and seventy-four incontinent residents were randomly selected in order to assess the effect of medical intervention (study group). A further 104 incontinent residents were selected to act as controls (control group). The vast majority of the study group showed evidence of chronic brain failure and 40% had impaired mobility. Almost half had been incontinent since admission. Urodynamic studies were required for management in only two (1.1%). Most (93%) were managed in accordance with a clinical diagnosis of an unstable bladder. There was a reduction in daytime incontinence in 40% of the study group, but this was matched by a reduction in 29% of the control group and the difference was not significant. The reduction in nocturnal incontinence in 41% of the treatment group was significantly different from 23% of the control group (P = 0.016)." ]

[ "7818255" ]

[ "Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis." ]

[ "A randomized, double-blinded, placebo-controlled, clinical trial of low-dose, weekly, oral methotrexate was performed in 60 patients with clinically definite chronic progressive multiple sclerosis (MS) attending a referral-based outpatient MS clinic. Study patients were 21 to 60 years old with a disease duration of longer than 1 year. Patients' Expanded Disability Status Scale scores were 3.0 to 6.5 (ambulatory with moderate disability). Patients were first stratified by Expanded Disability Status Scale scores, 3.0 to 5.5 and 6.0 to 6.5, and then were randomized to receive methotrexate or placebo treatment. Treatment consisted of weekly, oral, low-dose (7.5 mg) methotrexate or identical placebo for 2 years, followed by observation for as long as 1 year. A composite outcome measurement instrument was used and consisted of (1) Expanded Disability Status Scale, (2) ambulation index, (3) Box and Block Test, and (4) 9-Hole Peg Test. Failure of therapy was indicated by a designated change that was sustained for more than 2 months in one or more components of this composite measure. Significantly less progression of impairment as measured by validated tests of upper-extremity function was observed in the methotrexate treatment group in the absence of clinically significant toxicity. We conclude that low-dose, weekly, oral methotrexate offers a new, relatively nontoxic treatment option for patients with chronic progressive MS." ]

[ "12745558", "16616557", "15695996", "10485722", "16641396", "12767566", "7867399", "15987864" ]

[ "A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour.", "Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.", "Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial.", "Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.", "Vitamins C and E and the risks of preeclampsia and perinatal complications.", "Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas.", "Selenium supplement in the prevention of pregnancy induced hypertension.", "Multivitamin supplementation of HIV-positive women during pregnancy reduces hypertension." ]

[ "In a previous study from this institution, patients at high risk for preterm labour were screened for the presence of bacterial vaginosis (BV). When BV was present, they were randomised to receive either treatment (metronidazole) or placebo (vitamin C). There were significantly more patients with preterm labour in the metronidazole group. The aim of this double-blind randomised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour. Patients with a history of preterm labour in a preceding pregnancy were randomised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks' gestation. They attended a dedicated premature labour clinic. Significantly more women delivered before term in the group that received vitamin C, but there was no difference in the outcome of the babies between the two groups. Supplementation with vitamin C did not prevent premature labour.", "Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors.\n We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 .\n Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]).\n Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.", "We sought to determine the effect of supplemental antioxidant vitamins C and E on the rate of preeclampsia in high-risk pregnant women.\n Women at risk for preeclampsia (previous preeclampsia, chronic hypertension, pregestational diabetes, or multifetal gestation) were recruited at 14 to 20 weeks' gestation and randomly assigned to receive either 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily in addition to their regular prenatal vitamins. The primary outcome was the occurrence of preeclampsia. An estimated sample size of 220 women in each arm was determined to be necessary to demonstrate a 50% reduction in the rate of preeclampsia.\n Funding was terminated after 109 women had been recruited; 9 were lost to follow-up or withdrew. We analyzed data from the remaining 100 women to look for differences in outcome and to estimate the required sample size for future studies. The rate of preeclampsia was not different: 17.3% in women who received supplemental vitamins C and E, versus 18.8% in the placebo group. Assuming a baseline rate of preeclampsia in the placebo group between 15% and 20%, we can estimate that 500 to 950 women in each arm will be required to show a clinically important reduction in the rate of preeclampsia.\n The potential benefit of vitamin C and E supplementation to prevent preeclampsia in women with clinical risk factors is smaller than we estimated. Future studies of antioxidant vitamin supplementation in this population will require more than 500 women in each arm.", "Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia.\n 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study.\n Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002).\n Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.", "Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.\n We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.\n Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).\n Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).\n Copyright 2006 Massachusetts Medical Society.", "To observe the effect of the antioxidant lycopene on the occurrence of pre-eclampsia and intrauterine growth retardation in primigravida women.\n A total of 251 primigravida women were enrolled in this prospective, randomized controlled study in the second trimester. A total of 116 women were given oral lycopene (Group I) in a dose of 2 mg twice daily while 135 women were given a placebo (Group II) in the same dose until delivery. The criteria for recruitment included gestational age of 16-20 weeks, singleton pregnancy, absence of any medical complication and willingness on the part of the women to participate in the study. The women were followed-up until delivery for development of pre-eclampsia, mode of delivery and fetal outcome.\n The two groups were comparable in their maternal characteristics. Pre-eclampsia developed in significantly less women in the lycopene group than in the placebo group (8.6% vs. 17.7%, P=0.043 by chi-square test). Mean diastolic blood pressure was significantly higher in the placebo group (92.2+/-5.98 mmHg vs. 86.7+/-3.80 mmHg, P=0.012). Mean fetal weight was significantly higher in the lycopene group (2751.17+/-315.76 g vs. 2657+/-444.30 g, P=0.049). The incidence of intrauterine growth retardation was significantly lower in the lycopene group than in the placebo group (12% vs. 23.7%, P=0.033).\n The results of the present study suggest that the antioxidant lycopene reduces the development of pre-eclampsia and intrauterine growth retardation in primigravida women.", "The effect of selenium (Se) supplement on pregnancy was studied in 52 pregnant women with high risk factors of pregnancy induced hypertension (PIH). They were given natural Se dietetic liquid (100 micrograms/d) for 6-8 weeks during late pregnancy, and 48 controls were given placebo. They received similar routine prenatal care. The results revealed that Se supplement on the pregnant women prevented and decreased the incidence of PIH and gestational edema, and elevated the mother's blood Se level by 0.1008 +/- 0.091 ppm in the treated group while decreased by 0.0402 +/- 0.046 ppm in the control group (P < 0.01). The umbilical blood Se level was 0.2756 +/- 0.100 ppm in the treated group and 0.1544 +/- 0.051 ppm in the control (P < 0.01). The differences of the neonatal birth weight and the amount of postpartum hemorrhage between the two groups were not significant.", "Hypertension during pregnancy increases fetal growth retardation, preterm deliveries, and perinatal deaths, and yet its causes remain unclear. In HIV-infected women, preterm birth additionally increases the risk of HIV transmission to the infant. Oxidative stress and endothelial cell dysfunction of the placenta have been implicated in the development of hypertension during pregnancy. Vitamin intake can reduce oxidative stress and improve endothelial function. We therefore evaluated the effect of multivitamin (20 mg thiamine, 20 mg riboflavin, 25 mg B-6, 50 microg B-12, 500 mg C, 30 mg E, and 0.8 mg folic acid) and vitamin A supplements (30 mg beta-carotene plus 5000 IU preformed vitamin A) in relation to hypertension during pregnancy (systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg at any time during pregnancy). In a double-blind, placebo-controlled, randomized, clinical trial, conducted among 1078 HIV-positive pregnant Tanzanian women, those who received multivitamins were 38% less likely to develop hypertension during pregnancy than those who did not [relative risk (RR) = 0.62, 95% CI 0.40-0.94, P = 0.03]. There was no overall effect of vitamin A on hypertension during pregnancy (RR = 1.00, 95% CI 0.66-1.51, P = 0.98). Hypertension during pregnancy was more likely in women with high baseline systolic blood pressure (>120 vs. < or = 120 mm Hg) (RR = 6.02, 95%CI 2.59-13.97, P < 0.001), and those with higher mid-upper arm circumference (RR = 1.12, 95% CI 1.04-1.19, P = 0.002). Taking multivitamins containing vitamins B, C, and E during pregnancy may be an inexpensive and effective strategy to improve the health of the mother and baby." ]

[ "16832124" ]

[ "A randomized controlled trial of prophylactic antibiotics (co-amoxiclav) prior to embryo transfer." ]

[ "Bacterial contamination of the transfer catheter during embryo transfer is associated with poor clinical outcomes. Antibiotics at the time of embryo transfer may improve outcomes. We evaluated the effect of co-amoxiclav on the rates of bacterial contamination of transfer catheters and clinical pregnancy.\n On the day of oocyte collection, 350 patients were randomized, with sequentially numbered opaque-sealed envelopes containing treatment allocation assigned randomly by computer, to receive co-amoxiclav on the day before and the day of embryo transfer, or no antibiotics. Following transfer, the catheter tips were cultured and assessed to identify the organism(s) isolated and to quantify the level of the contamination. Couples were followed for 8 weeks to determine whether they had achieved clinical pregnancy. Outcome assessors were blinded to the treatment allocation, and the analysis was by intention to treat.\n Antibiotics significantly reduced catheter contamination rates (49.4 versus 62.3%, RR = 0.79, 95% CI: 0.64, 0.97, P = 0.03). There was no difference detected in clinical pregnancy rates between the two groups (36.0 versus 35.5%, P = 0.83) although there was a significant (P = 0.03) association between the level of bacterial contamination and clinical pregnancy rates.\n Co-amoxiclav reduces catheter contamination, but this is not translated into better clinically relevant outcomes such as clinical pregnancy rates. Our findings do not support the routine use of antibiotics at embryo transfer." ]

[ "19624440", "11641678", "9794673", "9764616", "17240231", "15954870", "15339772", "7936516", "2047061", "9662313", "16966110", "10389710", "15738009", "10838341", "12375540", "1448266", "11042301", "2406438", "15694083", "18222450", "8018638", "9731852" ]

[ "Randomised placebo-controlled trial of outpatient (at home) cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour--clinical trial with analyses of efficacy and acceptability. The IMOP study.", "Vaginally administered misoprostol for outpatient cervical ripening in pregnancies complicated by diabetes mellitus.", "The effects of mifepristone on cervical ripening and labor induction in primigravidae.", "Cervical ripening with mifepristone before labor induction: a randomized study.", "Outpatient vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening and labor induction postterm: a randomized controlled study.", "Outpatient misoprostol cervical ripening without subsequent induction of labor to prevent post-term pregnancy.", "Misoprostol outpatient cervical ripening without subsequent induction of labor: a randomized trial.", "Patient-administered outpatient intravaginal prostaglandin E2 suppositories in post-date pregnancies: a double-blind, randomized, placebo-controlled study.", "Sequential outpatient application of intravaginal prostaglandin E2 gel in the management of postdates pregnancies.", "Management of pregnancies beyond forty-one weeks' gestation with an unfavorable cervix.", "A randomized controlled trial of acupuncture for initiation of labor in nulliparous women.", "Prostaglandin E2 cervical ripening without subsequent induction of labor.", "Outpatient misoprostol compared with dinoprostone gel for preinduction cervical ripening: a randomized controlled trial.", "Attempted vaginal birth after cesarean section: a multicenter comparison of outpatient prostaglandin E(2) gel with expectant management.", "Outpatient cervical ripening with prostaglandin E2 and estradiol.", "Labor induction in women at term with mifepristone (RU 486): a double-blind, randomized, placebo-controlled study.", "Outpatient cervical ripening with intravaginal misoprostol.", "Intracervical prostaglandin in postdate pregnancy. A randomized trial.", "Use of misoprostol on an outpatient basis for postdate pregnancy.", "Outpatient cervical ripening with nitric oxide donor isosorbide mononitrate prior to induction of labor.", "Mifepristone for labour induction after previous caesarean section.", "Antepartum cervical ripening: applying prostaglandin E2 gel in conjunction with scheduled nonstress tests in postdate pregnancies." ]

[ "To determine whether isosorbide mononitrate (IMN), self-administered vaginally by women at home, improves the process of induction of labour.\n Randomised double blind placebo-controlled trial.\n Large UK maternity hospital.\n Nulliparous women with a singleton pregnancy, cephalic presentation > or = 37 weeks gestation, requiring cervical ripening prior to induction of labour.\n IMN (n = 177) or placebo (n = 173) self-administered vaginally at home at 48, 32 and 16 hours prior to the scheduled time of admission for induction.\n Admission to delivery interval and women's experience of induction of labour.\n IMN did not shorten the admission to delivery interval as compared with placebo [mean difference of -1.6 hours (95% CI -5.1,1.9, P = 0.37)], despite being more effective than placebo in inducing a change in Bishop score [mean difference of 0.65 (95% CI 0.14,1.17, P = 0.013)]. While both groups found the overall experience of home treatment to be positive, (mean score of 3.8/10 +/- 2.3/10 for the IMN group, where 1 = extremely good and 10 = not at all good) women in the placebo group found it marginally more positive than those in the IMN group (just over half a unit on a 10-point scale, P = 0.043). There were no differences between the groups in the pain or anxiety experienced or willingness to take the treatment in a subsequent pregnancy.\n IMN self-administered vaginally at home does not shorten admission to delivery interval despite a significant effect on cervical ripeness assessed using the Bishop score. However, women report positive views on cervical ripening at home, and the setting deserves further investigation.", "To compare the use of vaginally administered misoprostol to placebo for outpatient labor induction in patients with diabetes.\n In this double-masked, controlled clinical trial, pregnant women with diabetes and gestational age of >38(1/2) weeks were randomized to receive 25 microg misoprostol or placebo vaginally on days 1 and 4 of a 7-day outpatient cervical ripening period. If necessary, inpatient labor induction was managed by using a standard protocol.\n Of 120 women included in the study, 57 received misoprostol and 63 received placebo. Most of the women had been diagnosed with gestational (Class A) diabetes. Similar numbers of misoprostol and placebo-treated women delivered within 7 days of the first dose (31/57 [54%] vs 36/63 [57%], P =.63). The mean (+/-SEM) interval from induction to delivery was similar (8530.5 minutes +/-1439.7 minutes vs 6712.5 minutes +/-606.4 minutes, P =.23).\n Vaginally administered misoprostol was no more effective than placebo in reducing the need for inpatient labor induction or the induction-delivery interval. Outpatient cervical ripening with use of vaginally administered misoprostol was well tolerated.", "To compare the effects of 50 mg or 200 mg of oral mifepristone with placebo on cervical ripening and induction of labor in primigravid women at term with unfavorable cervices.\n This was a double-blind study in which 80 primigravidae at term with a modified Bishop score of 4 or less were randomly assigned to one of three treatment groups. They were assessed at 24-hour intervals for 72 hours, after which labor was induced if it had not occurred spontaneously.\n Two hundred milligrams of mifepristone resulted in a favorable cervix (with a Bishop score greater than 6 or in spontaneous labor) in significantly more women than placebo (P = .01). An improvement in cervical ripening was seen in the group given 50 mg of mifepristone, but this was not statistically significant. There were more cesarean deliveries performed for fetal distress in the group treated with 200 mg of mifepristone than placebo, but this was not statistically significant and was not associated with any differences between groups in terms of neonatal outcome.\n Mifepristone, a progesterone antagonist, is known to cause softening and dilation of the human early pregnant cervix and an increase in uterine activity. It is theoretically attractive for use as an adjunct in cervical priming and labor induction. In this study, 200 mg of mifepristone was significantly more likely to result in a favorable cervix than placebo.", "To determine the efficacy and safety of mifepristone for cervical ripening in post-term pregnancies.\n Women with post-term pregnancies and Bishop scores less than 6 were assigned randomly to mifepristone (41 patients) or placebo (42 patients). Mifepristone was given orally in a dose of 400 mg. Efficacy was assessed by change in the Bishop score within 48 hours after treatment; a score of 6 or greater was considered a \"strict\" success. An \"extended\" success rate was defined, including all patients with scores of at least 6 or those who delivered within 48 hours of treatment. Antenatal safety was assessed by fetal heart rate testing before and throughout labor. Neonatal safety was assessed by Apgar score, arterial or venous pH of cord blood, and blood glucose level during the first 48 hours. Analysis used Student t test for continuous variables, Kruskal-Wallis test for ordinal data, and chi2 for categoric variables.\n Strict success was achieved in 10 of 18 mifepristone patients (55%) evaluated for Bishop score on day 2 versus 8 of 29 placebo patients (27.5%) (P=.004). Extended success was achieved in 33 mifepristone patients (80.5%) and 21 placebo patients (50.0%) (P=.004). There were no statistical differences with regard to number of cesareans or fetal and neonatal safety.\n Mifepristone proved effective for cervical ripening and reduced the time to delivery compared with placebo, but it did not improve the rate of cesarean. Our study did not include enough pregnancies to reach conclusions about fetal or neonatal safety.", "Our aim was to examine the efficacy, safety, and acceptability of isosorbide mononitrate for cervical ripening and labor induction in women in an outpatient setting.\n Two hundred pregnant women of at least 42 weeks' gestation with an unripe cervix were randomly selected to receive vaginally either 40 mg isosorbide mononitrate or placebo tablets.\n Twenty-two women treated with isosorbide mononitrate went into labor within 24 hours compared to 8 women in the placebo group (P < .05). In women who did not go into labor, cervical status was similar in the 2 groups the next day. Headache was a common side effect. No maternal or fetal side effects of clinical importance were registered.\n Outpatient cervical ripening and labor induction with isosorbide mononitrate seems to be an effective, safe, and well tolerated procedure. The definitive clinical efficacy and safety needs to be evaluated in larger series of patients.", "Interventions that may help shorten the duration of pregnancy in an African setting where facilities for fetal monitoring in post-term pregnancy are limited, and induction is not without its hazards, are needed.\n To determine whether outpatient administration of intravaginal misoprostol safely decreases the interval to delivery in postdate pregnancies.\n Open randomized controlled trial.\n Zonal district hospitals, Kwale, Southern Nigeria (August 2000 to October 2001).\n Seventy-seven women were randomized at 40 weeks gestation to receive either 25 microg misoprostol intravaginally (38) or gentle cervical assessment only (39) on an outpatient basis. Subjects were then allowed to go into spontaneous labor unless an indication for induction developed.\n Interval to delivery, duration of labor, and incidence of side-effects.\n Misoprostol was associated with significant decrease in mean time to delivery (4.5 +/- 4.1 versus 7.4 +/- 5.2 days; P = 0.008), earlier gestational age at delivery (40.6 +/- 0.6 versus 41.4 +/- 0.05 weeks; P < 0.001) and shorter duration of active labor (6.1 +/- 4.0 versus 8.2 +/- 5.3 h; P = 0.028), without any significant increase in fetal distress, low Apgar score at delivery or other side-effects.\n Outpatient administration of low-dose misoprostol can safely shorten the length of gestation in postdate pregnancies.", "To estimate the effect of outpatient administration of a single dose of vaginal misoprostol at term on the interval to delivery in women with unfavorable cervices.\n Randomized, double blind, placebo-controlled trial comparing a single 25-microg outpatient intravaginal dose of misoprostol to placebo in pregnant women with Bishop scores less than 9 at 40 weeks or greater. After placement of the study medication, subjects were permitted to go into spontaneous labor unless an indication for induction developed. Analysis was by intent to treat. The interval to delivery, defined as the time from medication placement to delivery, was compared by Student t test and by survival analysis with the log-rank test.\n Thirty-three women were randomly assigned to receive misoprostol, and 35 were assigned to receive placebo. The mean interval to delivery was significantly less in the misoprostol group, 4.2 +/- 4.1 compared with 6.1 +/- 3.6 days, P =.04. The interval to delivery for only the nulliparous patients was significantly less in the misoprostol group, 4.2 +/- 4.0 compared with 7.2 +/- 3.7 days, P =.02. The survival curves for the interval to delivery were significantly different (P =.04 by log-rank test) with 4.1 days median interval to delivery for misoprostol compared with 9.2 days for placebo. There were no adverse outcomes in either group.\n A single 25-microg outpatient intravaginal dose of misoprostol is effective in decreasing the interval to delivery in women with unfavorable cervices at term.", "To shorten post-date pregnancies in a safe, effective manner by outpatient acceleration of cervical ripening.\n Eighty patients with uncomplicated pregnancies at or beyond 41 weeks' gestation and a cervical Bishop score less than 9 were randomized to daily self-administered, 2-mg intravaginal prostaglandin E2 (PGE2) or placebo suppositories. Each followed a standard post-date antepartum surveillance protocol. Patients were admitted for spontaneous labor or for induction if the Bishop score reached 9, antepartum testing was nonreassuring, exclusion criteria were fulfilled, or if the gestational age reached 44 weeks.\n Fewer suppositories were used in the PGE2 group (four versus seven; P = .006), resulting in earlier gestational age on admission (295 versus 297 days; P = .021) and lower antepartum testing charges ($476.97 versus $647.29; P = .001). Labor and delivery time was significantly decreased in nulliparas (10.7 +/- 5.1 versus 15.3 +/- 7.6 hours; P = .035).\n Daily low-dose, patient-administered PGE2 vaginal suppositories can decrease the gestational length and cost of uncomplicated post-date pregnancies by reducing the time to achieve a favorable cervix, the need for antepartum testing, and, potentially, post-date-related complications.", "A randomized blinded investigation was undertaken to determine the efficacy and safety of sequentially applied intravaginal prostaglandin E2 (PGE2) gel for accelerating cervical ripening in an outpatient setting in low-risk prolonged pregnancies. Fifty women with uncomplicated pregnancies at or beyond 41 weeks' gestation and Bishop scores below 9 received twice-weekly outpatient administration of gel containing 2.0 mg of PGE2 or placebo. Thirty nulliparas and 20 multiparas were enrolled. The PGE2 gel failed to improve cervical ripening over placebo, as judged by Bishop scores. There was no difference between the groups in gestational age on admission to the labor and delivery suite, number of gel applications, requirement for oxytocin, incidence of cesarean delivery, or neonatal outcome. Only two patients (4%) experienced regular uterine contractions after gel insertion; these subsided spontaneously in both. None of the subjects experienced labor, tetanic contractions, evidence of fetal distress, or any other side effects related to gel insertion. We conclude that PGE2 gel in this dosage may be used safely in an outpatient setting, but more frequent application or earlier initiation may be required to produce a clinical effect.", "Our purpose was to determine the optimal management of pregnancies beyond 41 weeks' gestation with a cervix unfavorable for induction.\n All uncomplicated pregnancies that reached 41 weeks' gestation with a Bishop score of < or = 4 were randomly assigned to one of three groups: (1) daily cervical examinations, (2) daily membrane stripping, or (3) daily placement of prostaglandin gel until 42 weeks.\n In 105 pregnancies the Bishop score on admission to labor and delivery was significantly greater in the groups receiving prostaglandin or stripping of the membranes versus the control group, whereas the converse was time of gestational age at delivery (p = 0.0001). Fewer patients required induction in the two treatment groups (20%, 17%) versus the control (69%) patients (p < 0.0001).\n Daily membrane stripping or daily placement of prostaglandin gel is successful in reducing the number of inductions at 42 weeks for postdatism.", "To evaluate the utility of outpatient acupuncture for labor stimulation.\n Nulliparous women at 39 4/7 weeks or greater with a singleton gestation and Bishop score of less than 7 were randomized to usual medical care (control group) versus usual care and three outpatient acupuncture treatments (acupuncture group). Each treatment consisted of eight needles applied to bilateral points LI4, SP6, UB31, and UB32. The primary outcome was time elapsed from the time of randomization to delivery. Secondary outcomes included rates of cesarean section and induction of labor. Medical records were abstracted for maternal demographic, medical, and delivery outcome data. A priori sample size calculation revealed that 56 women were required to detect a 72-hour difference in delivery time with a power of 83% and an alpha of 0.05. Student's t-test, Chi-square, and Kaplan-Meier statistics were used to compare groups.\n Fifty-six women were randomized and completed the study procedures. Race, age, gestational age, and cervical Bishop score were similar in both groups. Mean time to delivery occurred 21 hours sooner in the acupuncture group, but this difference did not reach statistical significance (p = 0.36). Compared to controls, women in the acupuncture group tended to be more likely to labor spontaneously (70% vs. 50%, p = 0.12) and less likely to deliver by cesarean section (39% vs. 17%, p = 0.07). Of women who were not induced, those in the acupuncture group were more likely to be delivered than the controls at any point after enrollment (p = 0.05).\n Acupuncture is well tolerated among term nulliparous women and holds promise in reducing interventions that occur in post-term pregnancies.", "To determine whether outpatient administration of intracervical prostaglandin (PG) E2 gel decreases the interval to delivery and duration of labor.\n A randomized, double-blind, placebo-controlled trial compared the intracervical placement of 0.5 mg PGE2 gel with placebo in 61 pregnant women at 38 weeks' or greater gestation with Bishop scores less than 9. Transvaginal cervical length, fetal fibronectin, and Bishop score were assessed before gel placement. Subjects were then allowed to go into spontaneous labor unless an indication for induction developed.\n Thirty women were assigned to PGE2 and 31 to placebo. There were no significant demographic differences between the groups and there were no differences in cervical length, fetal fibronectin status, or Bishop scores. Fifteen women in the PGE2 group and five in the placebo group went into labor and delivered within the first 2 days after gel placement (P = .007). The median interval to delivery was significantly shorter in the PGE2 group, at 2.5 days, compared with placebo, at 7 days (P = .02). Nulliparas in the PGE2 group had a median interval to delivery of 2 days, compared with 7 days for nulliparas receiving placebo (P = .03). Active phases of labor were significantly shorter in the PGE2 group and for women with a negative fetal fibronectin test who received PGE2.\n Outpatient administration of intracervical PGE2 gel shortened intervals to delivery and shortened labor.", "To determine whether a single outpatient dose of intravaginal misoprostol (versus intracervical dinoprostone gel) reduces the oxytocin use for induction. Despite the numerous trials examining misoprostol for induction, the efficacy of a single outpatient dose of misoprostol followed by oxytocin induction is unknown.\n Patients with a term, vertex, singleton pregnancy and a Bishop score of 6 or less were randomly assigned to receive misoprostol (n = 42, 0.25 microg intravaginally) or dinoprostone gel (n = 42, 0.5 mg intracervically) the evening before oxytocin induction. Patients were monitored for 3 hours after administration and discharged to home if fetal assessment was reassuring, for readmission the next morning for oxytocin. Primary outcomes were oxytocin dose, time, and dose intensity (dose divided by duration). Secondary outcomes were incidence of labor, uterine hyperstimulation, cesarean delivery, Apgar score. Statistics used were chi(2), Student t test, Mann-Whitney rank sum test, and Fisher exact test. P < .05 was accepted as statistically significant.\n A single dose of misoprostol significantly decreased the cumulative dose of oxytocin, the cumulative time of oxytocin administration, and the dose intensity of oxytocin (dose divided by time). Data are as follows (mean +/- standard error of the mean): oxytocin dose-dinoprostone 10,929 +/- 219 mU, misoprostol 6,081 +/- 170 mU, P = .008; oxytocin time-dinoprostone 798 +/- 11 minutes, misoprostol 531 +/- 11 minutes, P = .009; dose intensity-dinoprostone 11.3 +/- 0.1 mU/min, misoprostol 7.4 +/- 0.2 mU/min, P = .003. Misoprostol induced labor during the ripening period in 19 of 41 of patients, compared with 6 of 42 after dinoprostone (P = .002). There was no difference in cesarean delivery (dinoprostone, 8/42; misoprostol, 9/42; P = 1.00). There was no difference in short-term neonatal outcome. No patient had hyperstimulation or required cesarean delivery for nonreassuring fetal assessment during the ripening period.\n A single dose of misoprostol administered in the outpatient setting significantly decreases oxytocin use, largely due to labor within the ripening period.", "Objective: To compare the clinical effectiveness and safety of outpatient administration of an intracervical prostaglandin (PG) E(2) gel with expectant management for women with an unfavorable cervix who wish to attempt a vaginal birth after cesarean section.Study Design: This outpatient study was a randomized, multicenter investigation involving pregnant women at term with one previous low transverse cesarean section. Each had an unfavorable cervix (Bishop score </=4) and was a candidate for vaginal delivery. Those randomly assigned to receive the gel, rather than expectant management, were given a 0.5 mg dose of PGE(2) (Prepidil) intracervically at 39 weeks gestation. This cervical ripening treatment was repeated at weekly office visits for up to 3 doses.Results: Of the 294 cases, 143 received the gel while 151 underwent expectant management. No differences between the two groups were found for maternal demographics, race, parity, or predose Bishop score. The rates of repeat cesarean section did not differ (P =.68) with use of the gel (61, 42%) or with expectant therapy (48, 45%). The onset of active labor, the duration of labor among those delivering vaginally, and the 1-minute and 5-minute Apgar scores were not different between the two groups. No uterine rupture was apparent, and adverse effects during labor were as likely to occur in the two groups.Conclusions: Although its safety was confirmed for outpatient use and for persons with a prior cesarean delivery, intracervical prostaglandin E(2) gel did not improve the chance of a vaginal birth after a cesarean delivery.", "To determine whether weekly outpatient administration of prostaglandin gel or estrogen cream initiated labor in women with an unfavorable cervix.\n All uncomplicated pregnancies at term gestation who were candidates for a vaginal delivery with a Bishop score of < or = 6 were randomly assigned to receive on a weekly basis: prostaglandin E2 gel (n = 41); estrogen cream (n = 44); or inert lubricant jelly (n = 43).\n In the three groups no differences were observed among 128 subjects in the weekly Bishop scores, cervical dilatation or gestational age upon admission to the labor and delivery suite, the percentage of patients presenting with spontaneous labor or ruptured membranes, the number of post-date inductions or neonatal outcome.\n Weekly out-patient cervical ripening using either prostaglandin gel or estrogen in women with an unfavorable cervix at 37 weeks' gestation was no more effective than a placebo in Bishop score improvement or in preventing post-date inductions.", "To determine the efficacy and safety of mifepristone as an induction agent for the initiation of labor or as a cervical ripening agent in women at term.\n Our study group contained 120 women at term (after 37.5 weeks' amenorrhea) who had clear clinical indications for labor induction. They were randomized to receive either 200 mg of mifepristone or placebo on days 1 and 2 of a 4-day observation period, with labor induction planned for day 4. Eight patients, three treated with mifepristone and five receiving placebo, had to be excluded from the survey because they required cesareans for medical reasons (fetal distress or maternal complications) less than 12 hours after taking the first tablet.\n Forty-one subjects entered spontaneous labor, 31 treated with mifepristone and ten in the control group (P < .001). Forty-five needed cervical maturation with prostaglandins on day 4, 13 of whom had received mifepristone and 32 of whom had been given placebo (P < .001). Thirteen women treated with mifepristone and 13 who had taken placebo had mature cervices sufficient for classic labor induction with oxytocin and amniotomy. Patients who delivered vaginally needed a much lower amount of oxytocin when mifepristone had been given, and the mean time interval between day 1 of the survey and the onset of labor was also significantly shorter in this group.\n Although more studies are needed, we have found mifepristone to be a safe, efficient, and suitable induction agent for initiation of labor in women at term.", "To determine if outpatient cervical ripening using misoprostol can initiate labor within 48 hours of medication administration and to determine if time from medication administration to time of delivery is decreased using outpatient cervical ripening.\n Uncomplicated singleton, vertex pregnancies at 41 weeks' gestation or later with Bishop score of 4 or less were eligible for enrollment. Other inclusion criteria included intact membranes, less than eight uterine contractions per hour, a reactive nonstress test, and amniotic fluid index (AFI) over 5 cm. After randomization, 25 micro(cg) of misoprostol or placebo was placed within the posterior vaginal fornix. Patients were continuously monitored for 4 hours, then discharged if not in active labor. Patients returned in 24 hours for a repeat administration of the respective medication. Patients not delivered within 48 hours were admitted for inpatient induction of labor. Statistical analysis was performed with the Fisher, Student t, chi(2), and Mann-Whitney U tests, with P <.05 considered statistically significant.\n Among the 60 patients enrolled, 27 (45%) received misoprostol and 33 (55%) received placebo. The majority (24 of 27, 88.9%) of study group patients entered active labor within 48 hours after dosing, compared with 16.7% (five of 33) of placebo group patients (P <.001). The time from initial dose to delivery was significantly shorter in the misoprostol group (36.9 +/- 3.8 compared with 61.3 +/- 3.8 hours, P <.001).\n Intravaginal misoprostol is effective for outpatient cervical ripening. No adverse effects were encountered, although further study is required to determine the safety of this treatment regimen.", "A study was designed to see if incorporating intracervical administration of prostaglandin could affect the outcome of postdate pregnancies. All patients with verified dates, at least 41 6/7 weeks pregnant and enrolled in an antepartum testing schedule were randomized in a double-blind fashion to receive either 0.5 mg of prostaglandin E2 (PGE2) suspended in methylcellulose or a placebo of the gel alone. The gel was inserted directly into the cervical canal after the patient had a reactive/negative contraction stress test. The patient was then observed on an external fetal monitor for an hour before going home. A total of 23 patients received PGE2, and 20 received the placebo. Results were analyzed for the following: change in the Bishop score, lag time from dosage to delivery, spontaneous versus induced labor, cesarean section rate, length of labor and neonatal outcome. There were no significant differences between the groups except in the incidence of patients going into labor within 72 hours. The results indicate that, in general, 0.5 mg of intracervical PGE administered at greater than or equal to 41 6/7 weeks without subsequent oxytocin induction of labor did not appear to significantly alter the obstetric outcome.", "Within the obstetric community, several studies suggest that cervical ripening and labor induction after 40 weeks' gestation leads to improved maternal and neonatal outcomes. The most effective drug regimen to safely promote labor has not been determined.\n Forty-nine subjects followed in an outpatient obstetrical clinic with pregnancies of at least 40 weeks' gestation, and an unfavorable Bishop score were assigned randomly to receive oral misoprostol 50 or 25 microg every 3 days for a maximum of three doses.\n Twenty-three subjects received misoprostol 25 microg and 26 received 50 microg. The mean interval (+/-standard deviation) from start of cervical ripening to delivery was 2.4 days +/-0.3 vs. 3.9 days +/-0.7 for the 50 and 25 microg groups (P<0.05). No adverse events were noted. However, due to small sample size, less frequent adverse events may be missed. Type II errors cannot be excluded.\n In the prevention of postdate pregnancy, outpatients use of oral misoprostol 50 microg appears to result in earlier delivery, as compared to 25 microg.", "To examine the effectiveness and safety of outpatient vaginal administration of isosorbide mononitrate (IMN) to induce cervical ripening.\n A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted on 102 singleton term pregnant women with unfavorable cervices who were randomly assigned to receive outpatient intravaginal IMN or placebo before admission for induction of labor. The main outcome variable was time from hospital admission to delivery. Secondary outcomes included fetal and maternal morbidity, labor characteristics, and incidence of cesarean delivery.\n The admission-delivery interval was 13.45+/-6.63 and 20.12+/-8.19 h (P=0.0001) for the IMN and placebo groups, respectively. Of the IMN patients 62.75% needed prostaglandins for cervical ripening versus 90.2% with placebo (P=0.002). The incidence of tachysystole was significantly lower in the IMN group (P<0.05) but there were no significant differences in cesarean delivery rate, neonatal outcomes, and incidence of hyperstimulation.\n Outpatient use of IMN resulted in shorter admission to delivery interval, and was associated with less prostaglandin use and lower incidence of uterine tachysystole.", "To evaluate the efficacy and tolerance of mifepristone in women undergoing induction of labour at term after previous caesarean section.\n A prospective double blind placebo controlled trial.\n Thirty-two women at term (after 37.5 weeks' amenorrhea) who had had a previous caesarean delivery with a low transverse uterine incision. All women had a clear clinical indication for induction of labour with unfavourable cervical conditions (Bishop's score < 4). They were randomised to receive either 200 mg of mifepristone or placebo on days one and two of a four-day observation period.\n Thirteen women entered spontaneous labour: 11 were treated with mifepristone and two were in the control group (P < 0.01). Thirteen women, still with an unfavourable cervix on day four needed cervical ripening with vaginal tablets of prostaglandins. Of these, four had received mifepristone and nine the placebo. Mean oxytocin requirements were lower in the mifepristone group (P < 0.01) and the mean time interval between day one and start of labour was also significantly shorter in this group. Mode of delivery and neonatal outcome were similar in both groups.\n Induction of labour is facilitated in term women with prior caesarean section by the use of mifepristone. This induction agent appears safe and useful with no adverse events on the fetus or mother.", "Our purpose was to evaluate whether inserting prostaglandin E2 gel at the time of scheduled nonstress tests in patients with postdate pregnancies can decrease rates of intervention.\n A multicenter pilot study enrolled women with postdate pregnancies with Bishop score < or = 6 who were undergoing antepartum fetal heart rate testing. Patients were randomized in a double-blind fashion to receive either a prostaglandin E2 intracervical gel (Prepidil) or a placebo gel after each of their scheduled nonstress tests.\n There were no significant differences in the number of antepartum tests, labor inductions, or cesarean sections, the maximum oxytocin dosage, or the interval from admission to delivery in the prostaglandin E2 gel and placebo gel groups (n = 90). In the subset of patients with a Bishop score between 3 and 6 (63 patients), there were fewer inductions in the prostaglandin E2 group (30% vs 55%, P < .05).\n Application of prostaglandin E2 gel at the time of scheduled antepartum testing in patients with postdate pregnancies with unfavorable cervices decreased the induction rate only among patients with intermediate Bishop scores." ]

[ "3881220", "9846921", "9512207" ]

[ "Aminophylline versus doxapram in weaning premature infants from mechanical ventilation: preliminary report.", "Low-dose doxapram for treatment of apnoea following early weaning in very low birthweight infants: a randomized, double-blind study.", "Randomized, controlled, blinded trial of doxapram for extubation of the very low birthweight infant." ]

[ "A small, double-blind crossover study compared the efficacy of aminophylline and doxapram in ventilator weaning of eight premature infants recovering from respiratory distress syndrome (RDS). Although neither drug was significantly better than the other, four infants were weaned from mechanical ventilation after drug administration. It is suggested that drugs stimulating the respiratory center may aid in shortening the duration of mechanical ventilation in premature infants recovering from RDS.", "The effects of low-dose doxapram (0.5 mg kg(-1)h(-1)) in combination with caffeine were evaluated on apnoea frequency following weaning from mechanical ventilation, and on blood pressure, in very low birthweight (BW) premature infants. Twenty-nine infants with BW < or=1250 g, gestational age at birth (GA) <34 weeks and postnatal age <5 d, who required minimal respiratory support, were included. Following randomization, they received a loading dose of caffeine citrate and a continuous infusion of doxapram (doxapram, n=14) or placebo (n=15) was started. They were extubated 8 h after starting the infusion, which was continued for 5 d. During this period, weaning was well tolerated in both groups, apnoeas occurred less frequently and there was a greater increase in systolic blood pressure in infants treated with doxapram than in controls. Plasma doxapram levels were also higher than expected. It is therefore suggested that doxapram, even at low doses, should not be used during the first few days of life. Careful monitoring of blood pressure is required if doxapram is used later.", "The objective of the study was to determine whether administering doxapram by infusion to the very low birthweight infant, prior to extubation during the first 3 weeks of life, would increase the incidence of successful extubation. The study patients, 56 infants of less than 1251 g birthweight and less than 30 weeks' gestation, were entered in the first 3 weeks of life when lung disease had started to improve. A randomized blinded trial was performed, with infants receiving 3.5 mg kg(-1) doxapram bolus, followed by an infusion at 1 mg kg(-1) h(-1), or placebo. Weaning from positive pressure ventilation was standardized and extubation occurred after a 12 h trial of an intermittent mandatory ventilation (IMV) rate of 6 breaths min(-1), if PCO2 < 55 mmHg, pH > 7.26, and FiO2 < 0.45. Study drug was continued for 48 h postextubation, and the infants were placed on nasopharyngeal continuous positive airway pressure (CPAP) for 72 h postextubation. Extubation failure within the first 72 h after extubation was objectively defined in terms of acidosis (pH < 7.26), hypercarbia (PCO2 > 55 mmHg), excessive oxygen requirement (FiO2 > 0.8) or frequent apnoea (more than three in 12 h, or more than two requiring face mask IMV in 24 h). No difference was noted in the frequency of successful extubation between the groups. Fifteen infants in each group were successfully extubated before the 10th day of the study. In conclusion, when given in accordance with this protocol doxapram does not increase the likelihood of successful extubation in the very low birthweight infant. Increasing successful extubations in this group of infants will require other strategies." ]

[ "12874091", "17198647", "9469797", "1330398", "10212327", "12517683", "16147905", "15332347", "16148616", "17635851", "16015049", "19142758", "18600215", "9557932", "14618095", "17612946", "19005898", "19433778", "10480474", "19543080" ]

[ "Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects.", "[Chronotherapy with torasemide in hypertensive patients: increased efficacy and therapeutic coverage with bedtime administration].", "The effect on 24 h blood pressure control of an angiotensin converting enzyme inhibitor (perindopril) administered in the morning or at night.", "Effect of timing of administration on the plasma ACE inhibitory activity and the antihypertensive effect of quinapril.", "Morning versus evening amlodipine treatment: effect on circadian blood pressure profile in essential hypertensive patients.", "Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension.", "Administration time-dependent effects of valsartan on ambulatory blood pressure in elderly hypertensive subjects.", "Administration-time-dependent effects of doxazosin GITS on ambulatory blood pressure of hypertensive subjects.", "Treatment of non-dipper hypertension with bedtime administration of valsartan.", "Comparison of the efficacy of morning versus evening administration of telmisartan in essential hypertension.", "Comparison of a chronotherapeutically administered beta blocker vs. a traditionally administered beta blocker in patients with hypertension.", "Administration-time-dependent effects of olmesartan on the ambulatory blood pressure of essential hypertension patients.", "Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing.", "Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients.", "Differential effects of morning or evening dosing of amlodipine on circadian blood pressure and heart rate.", "Dose- and administration time-dependent effects of nifedipine gits on ambulatory blood pressure in hypertensive subjects.", "Comparison of the effects on ambulatory blood pressure of awakening versus bedtime administration of torasemide in essential hypertension.", "Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: improved blood pressure control with bedtime dosing.", "Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate.", "Reduction of morning blood pressure surge after treatment with nifedipine GITS at bedtime, but not upon awakening, in essential hypertension." ]

[ "This study investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin II receptor blocker. We studied 90 subjects (30 men and 60 women), 49.0+/-14.3 (mean+/-SD) years of age with stage 1 to 2 essential hypertension; they were randomly assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The highly significant blood pressure reduction after 3 months of treatment with valsartan (P<0.001) was similar for both treatment times (17.0 and 11.3 mm Hg reduction in the 24-hour mean of systolic and diastolic blood pressure with morning administration and 14.6 and 11.4 mm Hg reduction with bedtime administration; P>0.174 for treatment time effect). Valsartan administration at bedtime as opposed to on wakening resulted in a highly significant average increase by 6% (P<0.001) in the diurnal-nocturnal ratio of blood pressure; this corresponded to a 73% relative reduction in the number of nondipper patients. The findings confirm that valsartan efficiently reduces blood pressure throughout the entire 24 hours, independent of treatment time. They also suggest that time of treatment can be chosen according to the dipper status of a patient to optimize the effect of antihypertensive therapy, an issue that deserves further investigation.", "Torasemide is a high ceiling loop diuretic frequently used for treatment of heart failure, renal failure and hypertension, according to results mainly based on clinic blood pressure measurements, without proper evaluation of the 24-hour efficacy of the drug. Accordingly, we investigated the time-dependent antihypertensive efficacy of torasemide in hypertensive patients.\n We studied 58 patients with grade 1-2 essential hypertension (25 men and 33 women), 48.7 (11.9) years of age, randomly assigned to receive torasemide (5 mg/day) either upon awakening or at bedtime. Blood pressure was measured by ambulatory monitoring for 48 consecutive hours before and after 6 weeks of therapy.\n Efficacy of torasemide was significantly higher with bedtime dosing (11.2 and 8.0 mmHg reduction in the 24-hour mean of systolic and diastolic blood pressure, respectively) as compared to the administration of the drug on awakening (6.2 and 3.7 mmHg reduction in systolic and diastolic blood pressure). The percentage of patients with controlled ambulatory blood pressure after treatment was also higher after bedtime treatment (54% versus 27%). The time-response curves indicate a full 24-hour therapeutic duration only when torasemide was administered before bedtime. With regard to the safety profile, 2 patients presented secondary effects (abdominal pain, diarrhea) in morning dose, and 4 patients taking the drug at bedtime reported nicturia.\n A dose of 5 mg/day torasemide is effective for blood pressure reduction after bedtime administration. The differences in efficacy and therapeutic duration as a function of the circadian time of treatment with torasemide here documented should be taken into account when prescribing this loop diuretic for treatment of patients with essential hypertension.", "To determine the clinic and ambulatory blood pressure when the same dose of perindopril (4 mg) is administered in the morning (0900 h), or at night (2100 h), in particular, to determine whether the early morning blood pressure rise, the duration of effect and the pattern of response differed.\n Twenty male patients with diastolic blood pressure 95-110 mmHg when seated and 24 h mean ambulatory diastolic blood pressure > 85 mmHg after 4 weeks' placebo were allocated randomly to be administered 4 mg perindopril at 0900 h or at 2100 h. Clinic blood pressure (with the patient seated and erect) was measured 2 and 4 weeks after the therapy had been started and ambulatory blood pressure monitoring with a SpaceLabs device was performed for 26 h during week 4. The patients then crossed over to the other time of dosage and the measurements were repeated. The study was conducted from a hospital clinic.\n The clinic analysis concerned all 20 patients but the ambulatory analysis concerned 18 patients because the ambulatory blood pressure monitor data sets were inadequate for two patients. Compliance was high (97 +/- 3%), with a suggestion that it was better with the 0900 h dose. Clinic blood pressure (with the patient seated and erect) was lower under both regimes and the blood pressure with night-time administration of perindopril tended to be lower than that with daytime administration (P = 0.05-0.10). Twenty-four-hour mean, daytime and night-time means were lower with both doses than they were with placebo and did not differ. Both regimes reduced the early morning peak blood pressure rise and the effect tended to be greater with the 2100 h dose (P = 0.05-0.10). The 0900 h dose had an effect that persisted for > 24 h but the effect of the 2100 h dose had dissipated 18 h after the dose. There was no excessive night-time fall in blood pressure with the 2100 h dose. The trough : peak ratio with the 0900 h dose was 0.86 for systolic and 0.70 for diastolic blood pressure.\n The early morning blood pressure rise is reduced more when 4 mg perindopril is administered at 2100 h. However, the 2100 h dose regime does not reduce blood pressure over 24 h whereas 24 h control is achieved with the 0900 h dose. In clinical practice the 2100 h dose would have been titrated to the next dose range in more patients. This study indicates that the response profile obtained with an angiotensin converting enzyme inhibitor cannot be transformed from one dose time to another automatically and that chronobiology has important effects on a drug's action.", "To assess whether timing of administration can influence the antihypertensive effect of quinapril, 18 patients with hypertension were studied with noninvasive ambulatory blood pressure monitoring. Quinapril, 20 mg, was given at 8 AM or 10 PM for 4 weeks in a double-blind crossover fashion. To study the pattern of angiotensin converting enzyme (ACE) inhibition with the two treatment regimens, plasma ACE activity was measured in seven subjects 2, 4, 8, 12 and 24 hours after quinapril administration. The 24-hour blood pressure profiles showed a more sustained antihypertensive action with the evening administration of quinapril compared with the morning administration of quinapril; as with the morning administration, a partial loss of effectiveness was observed during nighttime hours. Measurement of ACE activity showed that evening administration caused a less pronounced but a more sustained decline of plasma ACE. These findings show that 20 mg quinapril given once daily is effective in lowering blood pressure levels throughout a 24-hour period. The evening administration seems to be preferable because it causes a more favorable modulation of ACE inhibition and therefore determines a more homogeneous 24-hour blood pressure control.", "OBJECTIVE: To determine the antihypertensive efficacy and the potential impact on circadian blood pressure pattern of morning versus evening administration of amlodipine to essential hypertensive patients. METHODS: Twelve mild-to-moderate essential hypertensives were investigated in this open, randomized cross-over study. Blood pressure and heart rate were measured by use of ambulatory blood pressure monitoring after a wash-out period of 1 week and after treatment schedules with 5 mg amlodipine once a day either at 0800 h or at 2000 h for 3 weeks. Effects were evaluated by linear and rhythm analysis using the ABPM-FIT program. RESULTS: Both morning and evening administrations of amlodipine significantly (P < 0.01) reduced the elevated systolic and diastolic blood pressures during daytime. However, due to baseline values being lower during night-time, a significant (P < 0.05) reduction was observed only in systolic, not in diastolic, blood pressure. Maximal blood pressure values were significantly (P </= 0.01) decreased by both treatment regimens, whereas nightly minimum values remained unchanged. The early morning rise in blood pressure was decreaseed after morning and slightly more pronounced aftger evening dosing of amlodipine. Though both amlodipine treatments more effectively reduced daytime blood pressure levels, the circadian profile was not greatly affected. Amlodipine treatment had no effect on heart rate. CONCLUSION: The results demonstrate that, independently from the dosing time, the long-acting calcium antagonist amlodipine sufficiently reduced blood pressure in essential hypertensive patients without increasing the nightly drop. The drug-induced decrase in the early morning rise in blood pressure may be advantageous in reducing the early morning cardiovascular risk.", "The efficacy and safety of a chronotherapeutic, graded-release diltiazem HCl extended-release (GRD) 120-, 240-, 360- and 540-mg dose administered once-daily at bedtime (10 PM) were evaluated in a 7-week randomized, double-blind comparison to placebo and to GRD 360 mg administered once-daily at 8 AM in 478 patients with moderate-to-severe essential hypertension.\n We assessed the change from baseline to end point in trough diastolic blood pressure (DBP) at 6 PM to 10 PM and in mean DBP from 6 AM to 12 noon between GRD 360 mg PM and GRD 360 mg AM, measured by ambulatory BP monitoring (ABPM).\n Bedtime doses of GRD showed dose-related mean reductions in trough DBP that were significant for GRD doses of 240 mg and higher. Bedtime GRD 360 mg was associated with a significantly greater reduction in mean DBP between 6 AM and 12 noon compared to morning GRD 360 mg with a least squares mean for treatment difference of -3.3 mm Hg (P =.0004). Similar dose-related and significant reductions in systolic BP (SBP) and heart rate (HR) were obtained. Incidence of adverse events (AEs) for all GRD groups (44.5%) was less than that obtained for the placebo group (49.3%). The 540-mg group showed an incidence of AEs (43.5%) similar to that observed for the 240-mg group (42.6%).\n The GRD dose-dependently significantly reduces BP and HR over the 24-h interval after once-daily bedtime dosing. Further greater reductions were obtained between 6 AM and 12 noon, when circadian BP is highest, compared to morning administration of the same dose. The 540-mg GRD was safe, well tolerated, and offers further therapeutic option for patients with severe hypertension who required additional BP control.", "Previous results have indicated that valsartan administration at bed-time, as opposed to upon wakening, improves the diurnal/nocturnal ratio of blood pressure (BP) toward a normal dipping pattern, without loss of 24 h efficacy. This ratio is characterized by a progressive decrease with aging. Accordingly, we investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin blocking agent, in elderly hypertensive patients. We studied 100 elderly patients with grade 1-2 essential hypertension (34 men and 66 women), 68.2+/-4.9 years of age, randomly assigned to receive valsartan (160 mg/d) as a monotherapy either upon awakening or at bed-time. BP was measured for 48 h by ambulatory monitoring, at 20 min intervals between 07:00 to 23:00 h and at 30 min intervals at night, before and after 3 months of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately determine the duration of sleep and wake spans to enable the accurate calculation of the diurnal and nocturnal means of BP for each subject. There was a highly significant BP reduction after 3 months of valsartan treatment (p < 0.001). The reduction was slightly larger with bed-time dosing (15.3 and 9.2 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively) than with morning dosing (12.3 and 6.3 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively). The diurnal/nocturnal ratio, measured as the nocturnal decline of BP relative to the diurnal mean, was unchanged in the group ingesting valsartan upon awakening (-1.0 and -0.3 for systolic and diastolic BP; p > 0.195). This ratio was significantly increased (6.6 and 5.4 for systolic and diastolic BP; p < 0.001) when valsartan was ingested at bed-time. The reduction of the nocturnal mean was doubled in the group ingesting valsartan at bed-time, as compared to the group ingesting it in the morning (p < 0.001). In elderly hypertensive patients, mainly characterized by a diminished nocturnal decline in BP, bed-time valsartan dosing is better than morning dosing since it improves efficacy during the nighttime sleep span, with the potential reduction in cardiovascular risk that has been associated with a normalized diurnal/nocturnal BP ratio.", "Previous studies have shown that a single nighttime dose of standard doxazosin, an alpha-adrenergic antagonist, reduces blood pressure (BP) throughout the 24 h. We investigated the administration-time-dependent effects of the new doxazosin gastrointestinal therapeutic system (GITS) formulation. We studied 91 subjects (49 men and 42 women), 56.7+/-11.2 (mean+/-SD) yrs of age with grade 1-2 essential hypertension; 39 patients had been previously untreated, and the remaining 52 had been treated with two antihypertensive medications with inadequate control of their hypertension. The subjects of the two groups, the monotherapy and polytherapy groups, respectively, were randomly assigned to receive the single daily dose of doxazosin GITS (4 mg/day) either upon awakening or at bedtime. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours just before and after 3 months of treatment. After 3 months of doxazosin GITS therapy upon awakening, there was a small and nonstatistically significant reduction in BP (1.8 and 3.2mm Hg in the 24 h mean of systolic and diastolic BP in monotherapy; 2.2 and 1.9mm Hg in polytherapy), mainly because of absence of any effect on nocturnal BP. The 24 h mean BP reduction was larger and statistically significant (6.9 and 5.9 mm for systolic and diastolic BP, respectively, in monotherapy; 5.3 and 4.5 mm Hg in polytherapy) when doxazosin GITS was scheduled at bedtime. This BP-lowering effect was similar during both the day and nighttime hours. Doxazosin GITS ingested daily on awakening failed to provide full 24h therapeutic coverage. Bedtime dosing with doxazosin GITS, however, significantly reduced BP throughout the 24h both when used as a monotherapy and when used in combination with other antihypertensive pharmacotherapy. Knowledge of the chronopharmacology of doxazosin GITS is key to optimizing the efficiency of its BP-lowering effect, and this must be taken into consideration when prescribing this medication to patients.", "Previous results have indicated that valsartan administration at bedtime, as opposed to upon wakening, may improve the diurnal: nocturnal ratio of blood pressure without loss in 24-h coverage and efficacy.\n To investigate the administration time-dependent antihypertensive efficacy of valsartan in non-dipper patients.\n We studied 148 non-dipper patients with grade 1-2 essential hypertension, aged 53.0+/-12.6 years, who were randomly assigned to receive valsartan (160 mg/day) as a monotherapy either on awakening or at bedtime. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per subject basis.\n The significant blood pressure reduction after 3 months of valsartan (P<0.001) was similar for both treatment times (13.1 and 8.5 mmHg reduction in the 24-h mean of systolic and diastolic blood pressure with morning administration; 14.7 and 10.3 mmHg with bedtime administration; P>0.126 for treatment-time effect). The diurnal: nocturnal ratio of blood pressure was significantly increased only when valsartan was administered before bedtime, which resulted in 75% of the patients in this group reverting to dippers, a significant increase in the percentage of patients with controlled blood pressure over 24 h, and a reduction in urinary albumin excretion.\n In non-dipper hypertensive patients, dosing time with valsartan should be chosen at bedtime, for improved efficacy during the nocturnal resting hours, as well as the potential associated reduction in cardiovascular risk.", "Valsartan administration at bedtime as opposed to on wakening improves the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Yet to be determined is whether this administration time-dependent efficacy is a class-related feature, characteristic of all angiotensin receptor blockers or specific only to valsartan. Terminal half-life is a major difference between angiotensin receptor blockers, being largest ( approximately 24 hours) for telmisartan. This trial investigated the administration time-dependent antihypertensive efficacy of telmisartan. We studied 215 patients with hypertension (114 men and 101 women), 46.4+/-12.0 years of age, randomly assigned to receive telmisartan (80 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured for 48 hours before and after 12 weeks of treatment. The significant blood pressure reduction after treatment was similar for both groups. Bedtime administration of telmisartan, however, was more efficient than morning dosing in reducing the nocturnal blood pressure mean. The sleep time-relative blood pressure decline was slightly reduced after telmisartan on awakening but significantly increased with bedtime dosing, thus reducing the prevalence of nondipping from baseline by 76%. Telmisartan administered at bedtime, as opposed to morning dosing, improved the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Nocturnal BP regulation is significantly better achieved with bedtime dosing of telmisartan. Results from this prospective trial suggest that these beneficial features of bedtime dosing may be class related for angiotensin receptor blockers. These results should be taken into account when prescribing this class of antihypertensive medication for treatment of essential hypertension.", "Increasing systolic blood pressure and heart rate during the early morning results in increased myocardial oxygen demand. The use of beta blockers during this period may decrease cardiac workload, particularly in beta-blocker sensitive patients. The impact of a new chronotherapeutic beta blocker was assessed in 44 hypertensive patients. Patients were randomized to delayed-release propranolol (INP) dosed at 10 p.m. or to traditionally dosed propranolol (ILA) dosed at 8 a.m. for 4 weeks, following which they were switched to the alternative formulation for 4 weeks. Thirty-four-hour ambulatory blood pressure monitoring and pharmacokinetic measurements were obtained. INP and ILA resulted in significant reductions in mean 24-hour blood pressure (-9.0/-6.9 mm Hg and -10.4/-7.7 mm Hg, respectively). The top 25% of responders to high-dose propranolol (sensitive patients) were compared on each formulation. Mean trough reductions were -8.0/-6.7 mm Hg and -7.6/-5.8 mm Hg, respectively. Mean blood pressure reductions in the beta-blocker sensitive patients (n = 11) between 6 a.m. and noon were -15.2/-11.9 mm Hg on INP and -8.0/-4.6 mm Hg on ILA. Heart rate reduction was -14.1 bpm and double product reduction was -3319 in the INP patients between 6 a.m. and 12 noon compared with -10.5 and -2209 in the ILA patients. This study suggests that INP and ILA are effective once-a-day beta blockers, but the use of delayed-release propanolol results in a greater reduction in double product between 6 a.m. and noon in beta-blocker sensitive patients than does traditionally dosed propranolol.", "Previous studies established that a single daily dose of olmesartan remains effective for the entire 24 h without alteration of the day-night blood pressure (BP) pattern. On the other hand, the administration of valsartan or telmisartan at bedtime, as opposed to upon wakening, improves the sleep-time relative BP decline toward a greater dipper pattern without loss of 24 h efficacy. Yet to be determined is whether this administration-time-dependent efficacy is a class-related feature, characteristic of all angiotensin-receptor-blocker (ARB) medications. We studied 123 grade 1 and 2 hypertensive patients, 46.6+/-12.3 yrs of age, randomly assigned to receive olmesartan (20 mg/day) as a monotherapy either upon awakening or at bedtime for three months. BP was measured by ambulatory monitoring for 48 consecutive hours before and after treatment. The 24 h BP reduction was similar for both treatment times. Administration of olmesartan at bedtime, however, was significantly more efficient than morning administration in reducing the nocturnal BP mean. The sleep-time relative BP decline was slightly reduced with olmesartan ingestion upon awakening but significantly increased with ingestion at bedtime, thus reducing the prevalence of non-dipping from baseline by 48%. Olmesartan administration at bedtime, as opposed to in the morning, improved the awake/asleep BP ratio toward a greater dipper pattern without loss of 24 h efficacy. Nocturnal BP regulation was significantly better achieved with bedtime as compared to morning dosing of olmesartan. These effects are comparable to those previously reported for valsartan and telmisartan, thus suggesting that they may be class-related features of ARB medications in spite of differences in their half-life kinetics. These administration-time-dependent effects should be taken into account when prescribing ARB medications for treatment of essential hypertension.", "Previous studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium-channel blockers (CCBs), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the administration-time dependent antihypertensive efficacy of the slow-release, once-a-day nifedipine gastrointestinal-therapeutic-system (GITS) formulation.\n We studied 180 untreated hypertensives (86 men and 94 women), 52.5 +/- 10.7 years of age, randomly assigned to receive nifedipine (30 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured for 48 h before and after 8 weeks of treatment.\n The BP reduction after treatment was significantly larger with bedtime dosing mainly during night time sleep (P < 0.012). The number of patients with controlled ambulatory BP after treatment was greater with bedtime than morning treatment (P = 0.016). The baseline prevalence of nondipping was unaltered after ingestion of nifedipine on awakening, but reduced from 51 to 35% after bedtime dosing (P = 0.025). The morning surge of BP, a risk factor for stroke, was significantly reduced (P < 0.001) only after bedtime administration of nifedipine. Bedtime in comparison to awakening-time ingestion of nifedipine was also associated with a reduction in the incidence of edema from 13 to 1% (P < 0.001).\n The increased efficacy on ambulatory BP as well as the significantly reduced prevalence of edema after bedtime as compared to morning ingestion of nifedipine should be taken into account when prescribing this medication to patients with essential hypertension.", "To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily.\n Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study.\n After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment.\n Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening).\n Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.", "To compare the effects of morning and evening dosing of amlodipine on both circadian blood pressure (BP) and heart rate (HR) in mild-to-moderate essential hypertension.\n A perspective, double-blind, randomized, crossover design with dose titration.\n Sixty-two patients recruited in the study were aged 21-77 years and had mild-to-moderate essential hypertension. At the end of a 2-week single-blind, placebo run-in period, eligible patients were randomly assigned to morning (7 AM) and evening (9 PM) amlodipine treatment. The initial dose was 5 mg. After 2 weeks of double-blind therapy, patients with a seated diastolic blood pressure > or =90 mm Hg had their doses titrated upward to 10 mg, while the other patients remained on their original 5 mg doses for another 4 weeks period, than crossover to the alternate dosing regimen for 6 additional weeks. The 24-h ambulatory monitoring was performed at baseline and at 6 and 12 weeks after randomization.\n 24-h diastolic BP load (11.0 +/- 17.5% vs. 6.5 +/- 9.1%, P < 0.05) and night-time BP load (28.5 +/- 31.4%/17.7 +/- 28.2% vs. 20.0 +/- 27.9%/9.2 +/- 17.8%, P < 0.05/0.05) were significantly greater with evening dosing compared with morning dosing. Nocturnal fall of BP was greater with morning dosing than with evening dosing (9.8 +/- 6.7/7.4 +/- 5.3 vs. 6.7 +/- 6.6/5.4 +/- 5.4 mm Hg, P < 0.01/0.05). Percentage of nocturnal BP fall was greater with morning dosing versus with evening dosing (7.9 +/- 5.3%/9.6 +/- 6.8% vs. 5.4 +/- 7.0%/7.0 +/- 6.9%, P < 0.01/0.05).\n Morning administered amlodipine had a better effect on the circadian BP compared with evening administrated amlodipine in mild-to-moderate essential hypertension.", "Previous chronotherapy studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium channel blockers (CCB), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the antihypertensive efficacy and safety profile of the slow-release, once-a-day nifedipine gastrointestinal therapeutic system (GITS) formulation administered at different times with reference to the rest-activity cycle of each participant. We studied 80 diurnally active subjects (36 men and 44 women), 52.1+/-10.7 yrs of age, with grade 1-2 essential hypertension, who were randomly assigned to receive nifedipine GITS (30 mg/day) as a monotherapy for eight weeks, either upon awakening in the morning or at bedtime at night. Patients with uncontrolled BP were up-titrated to a higher dose, 60 mg/day nifedipine GITS, for an additional eight weeks. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours before and after therapy with either dose. The BP reduction after eight weeks of therapy with the lower dose of 30 mg/day was slightly, but not significantly, larger with bedtime dosing. The efficacy of 60 mg/day nifedipine GITS in non-responders to the initial 30 mg/day dose was twice as great with bedtime as compared to morning dosing. Moreover, bedtime administration of nifedipine GITS reduced the incidence of edema as an adverse event by 91%, and the total number of all adverse events by 74% as compared to morning dosing (p=0.026). Independent of the time of day of administration, a single daily dose of 30 mg/day of nifedipine GITS provides full 24 h therapeutic coverage. The dose-dependent increased efficacy and the markedly improved safety profile of bedtime as compared to morning administration of nifedipine GITS should be taken into account when prescribing this CCB in the treatment of essential hypertension.", "Torasemide is a high-ceiling loop diuretic frequently used in the treatment of congestive heart failure, renal failure, and hypertension. Low doses of torasemide (2.5 to 5 mg/day) do not elevate 24 h natriuresis, and they constitute effective monotherapy for mild-to-moderate uncomplicated essential hypertension according to results based on clinic blood pressure (BP). However, there has yet to be a proper evaluation of its 24 h efficacy or potential dependency of effects according to the circadian time of treatment. Accordingly, this trial investigated the administration time-dependent efficacy of torasemide in uncomplicated essential hypertensive patients. We studied a total of 113 grade 1 and 2 hypertensive patients, 51.7+/-10.6 yrs of age, randomly assigned to receive torasemide (5 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured by ambulatory monitoring for 48 consecutive hours before and after six weeks of treatment. The efficacy of torasemide was significantly greater with bedtime dosing (i.e., 14.8 and 9.5 mmHg reduction in the 24 h mean systolic and diastolic BP, respectively) as compared with morning dosing upon awakening (i.e., 6.4 and 3.4 mmHg reduction in mean systolic and diastolic BP; p<0.001 between the two treatment-time groups). The percentage of patients with controlled ambulatory BP after treatment was also higher after bedtime treatment (64 vs. 23%; p<0.001). Safety and tolerability were comparable between the two treatment-time groups. A dose of 5 mg/day torasemide is more effective for BP reduction for uncomplicated essential hypertensive patients when ingested at bedtime than in the morning upon arising. The difference in antihypertensive efficacy as a function of the circadian dosing-time of torasemide here documented should be taken into account when prescribing this loop diuretic to treat essential hypertensive patients.", "Clinical studies have demonstrated a different effect on blood pressure of some angiotensin-converting enzyme inhibitors when administered in the morning versus the evening. Their administration at bedtime resulted in a higher effect on nighttime blood pressure as compared with morning dosing. This study investigated the administration time-dependent effects of ramipril on ambulatory blood pressure. We studied 115 untreated hypertensive patients, 46.7+/-11.2 years of age, randomly assigned to receive ramipril (5 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured for 48 hours before and after 6 weeks of treatment. The blood pressure reduction during diurnal activity was similar for both treatment times. Bedtime administration of ramipril, however, was significantly more efficient than morning administration in reducing asleep blood pressure. The awake:asleep blood pressure ratio was decreased after ramipril on awakening but significantly increased toward a more dipping pattern after bedtime dosing. The proportion of patients with controlled ambulatory blood pressure increased from 43% to 65% (P=0.019) with bedtime treatment. Nocturnal blood pressure regulation is significantly better achieved at bedtime as compared with morning administration of ramipril, without any loss in efficacy during diurnal active hours. This might be clinically important, because nighttime blood pressure has been shown to be a more relevant marker of cardiovascular risk than diurnal mean values. The change in the dose-response curve, increased proportion of controlled patients, and improved efficacy on nighttime blood pressure with administration of ramipril at bedtime should be taken into account when prescribing this angiotensin-converting enzyme inhibitor for treatment of essential hypertension.", "The time of administration of once-daily antihypertensive agents may have a significant impact on blood pressure control during awake and sleep periods. Using 24-h ambulatory monitoring, we compared the effects of morning and evening dosing of the long-acting dihydropyridine calcium channel blocker, nisoldipine extended-release (ER), on circadian blood pressure (BP) and heart rate in patients with mild-to-moderate hypertension. After completing a 3-week placebo run-in period, 85 patients were randomized to morning versus evening nisoldipine ER treatment at a fixed 20-mg dose. Patients were treated for 4 weeks, followed by crossover to the alternate dosing regimen for 4 additional weeks. Twenty-four-hour ambulatory monitoring was performed at baseline and at 4 and 8 weeks after randomization. Awake and sleep times were determined by electronic activity recorders (Actigraphy). Similar least-squares (+/-SE) mean changes from baseline in 24-h BP (systolic BP/diastolic BP: -11.9/-7.4 +/- 0.6/0.5 v -11.6/-6.5 +/- 0.6/0.5 mm Hg) and heart rate (1.0/1.7 +/- 0.4/0.4 beats/min) occurred with morning and evening administration, respectively. A significantly greater effect on awake diastolic BP (systolic BP/diastolic BP: -12.6/-8.1 +/- 0.7/0.4 v -11.3/-6.4 +/- 0.7/0.4 mm Hg; P = .16/.01) was observed with morning dosing compared with evening dosing. In addition, small increases in sleep and early morning heart rate were seen with evening compared with morning administration of nisoldipine (sleep, 3.1 +/- 0.4 v 0.4 +/- 0.4 beats/min; P < .001; early morning, 3.5 +/- 0.7 v 0.5 +/- 0.7 beats/min; P = .002). These differential effects on awake BP and sleep heart rate were also observed in patients who had normal (dippers) and elevated (nondippers) BP values during sleep. Appropriate evaluation of the efficacy and safety of long-acting antihypertensive agents is essential when evening administration is being considered. In the present study, the timing of nisoldipine ER administration had no effect on mean changes in BP and heart rate over a 24-h period. However, nisoldipine ER had some differential effects during sleep and awake periods with morning relative to evening dosing.", "The extent of morning blood pressure (BP) surge upon wakening has been associated with increased incidence of stroke and cardiovascular mortality. This trial investigated the antihypertensive efficacy and effects on the morning BP surge of awakening versus bedtime administration of nifedipine in essential hypertension.\n We studied 238 previously untreated hypertensive patients (108 men and 130 women), 53.3+/-11.4 years of age, randomly assigned to receive nifedipine (30 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured for 48 h before and after 8 weeks of treatment.\n The BP reduction after the treatment was significantly greater with bedtime dosing (P<0.001). The proportion of patients with controlled ambulatory BP thus increased from 28 to 43% (P = 0.019) with bedtime treatment. The sleep time relative BP decline was unchanged after morning treatment, but increased toward a more dipping pattern after bedtime dosing (P = 0.026 between groups). The morning BP surge was unchanged after the administration of nifedipine upon awakening (1.4/1.2 mmHg reduction in systolic/diastolic BP surge, P>0.270), but significantly reduced after bedtime dosing (6.2/4.4 mmHg reduction, P<0.001).\n Nifedipine efficiently reduces BP for the entire 24 h and to a significantly larger extent after bedtime administration. The significant added efficacy on reducing night-time BP, the decrease in the prevalence of a nondipper BP pattern, and the significant decrease in morning BP surge (all relevant markers of cardiovascular morbidity and mortality) of bedtime as compared with morning administration, consistently indicate that nifedipine should preferably be administered at bedtime in patients with essential hypertension." ]

[ "10326778" ]

[ "Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease." ]

[ "Acute nicotine injections have been found to improve attentional performance in patients with Alzheimer's disease (AD), but little is known about chronic nicotine effects.\n The present study was undertaken to evaluate the clinical and neuropsychological effects of chronic transdermal nicotine in Alzheimer's disease subjects over a 4-week period.\n The double-blind, placebo controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period. Patients wore the nicotine patch (Nicotrol) for 16 h a day at the following doses: 5 mg/day during week 1, 10 mg/day during weeks 2 and 3 and 5 mg/day during week 4. The eight subjects had mild to moderate AD and were otherwise healthy.\n Nicotine significantly improved attentional performance as measured by the Conners' continuous performance test (CPT). There was a significant reduction in errors of omission on the CPT which continued throughout the period of chronic nicotine administration. The variability of hit reaction time (reaction time for correct responses) on the CPT was also significantly reduced by chronic nicotine. Nicotine did not improve performance on other tests measuring motor and memory function.\n The sustained improvement in attention found in this study with nicotine dermal patches is encouraging. However, the lack of detected effects of nicotine treatment on other cognitive and behavioral domains in this study leaves questions concerning the clinical impact of nicotinic treatment in Alzheimer's disease. The modest size of this study limited statistical power which may have been needed to detect more subtle but clinically significant cognitive effects. Higher doses of nicotine, other nicotinic ligands or combination treatment of nicotine with other therapies may be efficacious for producing broader therapeutic effects." ]

[ "6368412", "3382333", "3554684", "3351998", "7331802", "1762007", "1622057", "7451515", "3182882" ]

[ "Intertrochanteric fractures: a comparison between fixation with a two-piece nail plate and Ender's nails.", "Intertrochanteric fracture of the hip. Comparison of nail-plate fixation and Ender's nailing.", "[Pertrochanteric fractures. Comparison between 2 surgical methods of internal fixation].", "A comparison of nail-plate fixation and Ender's nailing in pertrochanteric fractures.", "Trochanteric and subtrochanteric fractures. The operative results in a prospective and comparative study of Ender nailing and McLaughlin Osteosynthesis.", "Treatment of intertrochanteric fractures: comparison of Ender nails and sliding screw plates.", "Clinical features and walking ability in the early postoperative period after treatment of trochanteric hip fractures. Results with special reference to fracture type and surgical treatment.", "The use of Ender's pins in extracapsular fractures of the hip.", "Unstable intertrochanteric fractures of the hip. Treatment with Ender pins compared with a compression hip-screw." ]

[ "The progress of 182 patients who presented with intertrochanteric fractures was followed over a six month period. Eighty-seven patients were treated using Thornton/McLaughlin nail plates and 95 were treated using Ender's intramedullary nails. Each fracture was classified according to radiological position and mechanical stability. The results show that the more unstable fractures are more likely to develop unsatisfactory results. Post operatively, the different mechanical complications have been recorded at various stages. Those fractures fixed with a nail plate tended to develop varus deformity resulting from either bony collapse around the implant or implant failure, whereas those fixed with Ender's nails did not develop deformity at the fracture site but encountered distal migration of the nails at the knee. The use of a classification system in predicting post operative mechanical complications is considered, and the comparative merits and disadvantages of the two fixation systems is discussed, with suggestions for improvement in operative technique.", "Between April 1979 and August 1983, 201 patients with intertrochanteric fractures of the hip were admitted to Haife Medical Center (Rothschild), Israel. These patients were randomely divided into two groups: 104 patients underwent fixation with a compression screw and plate (Richard's Co.) and 97 patients underwent fixation with Ender's nails. The results of both groups were analyzed and evaluated clinically, economically, and socially. There were differences in operative time, incidence of infection, local complications, and functional capacity, but, on the other hand, no difference in the length of hospital stay. The perioperative mortality was significantly higher in the group that underwent fixation with Ender nails (seven to one), but the overall mortality was the same for both groups. The advantages of the Ender method are a quicker surgical procedure, diminished blood loss, and practically no risk of deep infection. The fixation with compression screw and plate assures a better anatomical reduction of the hip with fewer local complications and a better functional result, but carries a higher risk of infection.", "nan", "A randomized comparison was made of condylocephalic (Ender) nails and a nail-plate technique (McLaughlin) for fixation of trochanteric fractures, to evaluate the consumption of acute hospital bed-days, number of reoperations, peroperative blood loss, and operation time. Reoperations were performed in 30% of the Ender group and in 10% of the McLaughlin group and blood loss was doubled for the McLaughlin method. Our study has shown, that in our hands, patients operated on with Ender nails had more reoperations, but in spite of this the total cost, in the form of days in hospital or operation time was not increased.", "A comparative and prospective study was performed in order to evaluate the advantages or disadvantages of the Ender operation in comparison with the McLaughlin technique. The series included 145 patients, 72 operated by the Ender method, and 73 by the McLaughlin method. There were no differences between the two groups as regards anaesthesia time, operation time, mean stay in hospital, morbidity and mortality. Technical problems were encountered in 40 of the Ender operated fractures (56 per cent), whereas the figure for the patients treated with the McLaughlin method was 17 (23 per cent). Ten (14 per cent) patients in the Ender group but only 2 (3 per cent) in the McLaughlin group needed re-operation. Three deep infections occurred in the McLaughlin group, but non in the Ender group. It was concluded that the only advantage which could be demonstrated in the Ender group was a low infection rate. Many disadvantages were revealed, the most outstanding being the many technical problems encountered and the great number of re-operations required.", "The results of two fixation devices for the treatment of intertrochanteric fractures were compared in 220 patients--163 women and 57 men with a mean age of 81 +/- 10 years. One hundred and one patients were randomized to Ender nailing and 119 to fixation with a sliding screw plate (SSP). The two treatment groups were equal with respect to important preinjury variables. The two methods did not differ in operating time or perioperative blood loss. The proportions of good reduction of the fractures and of good positioning of the internal fixation devices were equal in the two groups. But the complication rate and the reoperation rate were more than twice as high in the Ender group than in the SSP group. The outcome at 1-year follow-up was approximately equal in the two groups.", "The purpose of this study was to analyze the functional outcome during the early postoperative period (six weeks) in patients with trochanteric fractures. A consecutive series of 149 patients were randomized to treatment with either the DHS or Ender operative technique. 120 patients were available at review six weeks after surgery. Groups were comparable with respect to age (mean 77 years), sex ratio (73% women), type of fracture (59% and 55% unstable), experience level of the surgeon, prefracture health condition and ambulatory status. During follow-up eight patients died and there were 19 complications of neurologic and cardiovascular types equally spread among the two groups. All four infections were found in the DHS group. Orthopaedic hospital stay averaged 19 days and more patients in the Ender group could return to their previous home at time of discharge. At the six week visit 14% in the Ender group compared to 33% in the DHS group had not recovered functional walking distance (less than 15 m). All patients in the Ender group managed to walk, but 11% of the patients in the DHS group could not walk. Walking ability was most impaired for unstable fractures. It is concluded that the Ender technique will involve less operative trauma (shorter operations with less blood loss) and in the early postoperative period it can provide better conditions for walking and less need for further hospitalization than the DHS technique.", "In October 1976 a randomized, paired, prospective study comparing the compression sliding hip screw with Ender's pins in the treatment of extracapsular hip fractures was begun on the orthopaedic service at San Francisco General Hospital. The results in 100 patients with a minimum follow-up of six months showed that Ender's procedure required less operative time, had less blood loss, and had a lower postoperative incidence of medical complications. A 26 per cent incidence of technical problems with Ender's pins (such as postoperative backing-out of the pin) required reoperation in 16 per cent of the patients compared with an 8 per cent rate of reoperation in patients treated with the compression screw. The majority of these complications occurred in unstable fractures. There were no deep infections in the patients with Ender's pins but a 6 per cent incidence of deep infection was seen in those with the hip screws. There were no non-unions in either group. Although hip function at follow-up was equal in both groups, there was a 41 per cent incidence of postoperative pain and stiffness of the knee in the group with Ender's pins. It is our opinion that Ender's pins are a valuable addition to the armamentarium of surgeons treating extracapsular fractures of the hip and are ideally suited for elderly patients with stable fractures, particularly if the surgical risk is high. They must be used with caution in unstable fractures and postoperative protection in traction may be necessary. However, the occasional external rotation deformity and the high incidence of problems with the knee makes their use in younger, more active patients less desirable than the compression hip screw unless their unique advantages justify their use.", "In a prospective, consecutive, randomized study of the treatment of unstable intertrochanteric fractures of the hip, the use of Ender pins was compared with the use of the compression hip-screw. There were more than 100 patients in each treatment group. The patients who were alive six months postoperatively were evaluated. The number of secondary operations was much higher in the patients who were treated with Ender pins, and a considerably higher number of those patients had loss of fixation. The use of Ender pins that were too long and a history of a fracture before the operation in which Ender pins were used were statistically significant predictors of secondary operations." ]

[ "16564618", "17133529", "17886555", "17872930", "19920718", "12544752", "19247545", "18223016", "12595874", "19460131", "20018567", "17101886", "15026508", "17039098", "16495011", "19801069", "14746870", "17123186", "16315281", "11601430", "11588611", "18047871", "20633407", "21170277", "18779511", "19594842", "17271198", "16955313", "12138303", "16753335" ]

[ "A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury.", "A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia.", "Reduction of intractable deafferentation pain due to spinal cord or peripheral lesion by high-frequency repetitive transcranial magnetic stimulation of the primary motor cortex.", "Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia.", "Transcranial DC stimulation coupled with TENS for the treatment of chronic pain: a preliminary study.", "Immediate influence of transcranial electrostimulation on pain and beta-endorphin blood levels: an active placebo-controlled study.", "Pain reduction using transcranial electrostimulation: a double blind \"active placebo\" controlled trial.", "Motor cortex rTMS in chronic neuropathic pain: pain relief is associated with thermal sensory perception improvement.", "The amelioration of the suffering associated with spinal cord injury with subperception transcranial electrical stimulation.", "Low-frequency transcranial magnetic stimulation in patients with fibromyalgia and major depression.", "Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis.", "Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain.", "Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain.", "The treatment of fibromyalgia with cranial electrotherapy stimulation.", "Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex.", "Effect of repetitive transcranial magnetic stimulation over the hand motor cortical area on central pain after spinal cord injury.", "Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I.", "Using cranial electrotherapy stimulation to treat pain associated with spinal cord injury.", "Treatment of chronic visceral pain with brain stimulation.", "Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex.", "Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex.", "The effect of a series of repetitive transcranial magnetic stimulations of the motor cortex on central pain after spinal cord injury.", "A preliminary study of transcranial direct current stimulation for the treatment of refractory chronic pelvic pain.", "Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial.", "Pain relief by rTMS: differential effect of current flow but no specific action on pain subtypes.", "A pilot study investigating the effects of fast left prefrontal rTMS on chronic neuropathic pain.", "Temporary pain relief using transcranial electrotherapy stimulation: results of a randomized, double-blind pilot study.", "[Central and peripheral deafferent pain: therapy with repetitive transcranial magnetic stimulation].", "Repetitive transcranial magnetic stimulation for the treatment of chronic pain - a pilot study.", "Transcranial magnetic stimulation for pain control. Double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy." ]

[ "Past evidence has shown that motor cortical stimulation with invasive and non-invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non-invasive brain stimulation--transcranial direct current stimulation (tDCS)--on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity.", "Recent evidence suggests that fibromyalgia is a disorder characterized by dysfunctional brain activity. Because transcranial direct current stimulation (tDCS) can modulate brain activity noninvasively and can decrease pain in patients with refractory central pain, we hypothesized that tDCS treatment would result in pain relief in patients with fibromyalgia.\n Thirty-two patients were randomized to receive sham stimulation or real tDCS with the anode centered over the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC) (2 mA for 20 minutes on 5 consecutive days). A blinded evaluator rated the patient's pain, using the visual analog scale for pain, the clinician's global impression, the patient's global assessment, and the number of tender points. Other symptoms of fibromyalgia were evaluated using the Fibromyalgia Impact Questionnaire and the Short Form 36 Health Survey. Safety was assessed with a battery of neuropsychological tests. To assess potential confounders, we measured mood and anxiety changes throughout the trial.\n Anodal tDCS of the primary motor cortex induced significantly greater pain improvement compared with sham stimulation and stimulation of the DLPFC (P < 0.0001). Although this effect decreased after treatment ended, it was still significant after 3 weeks of followup (P = 0.004). A small positive impact on quality of life was observed among patients who received anodal M1 stimulation. This treatment was associated with a few mild adverse events, but the frequency of these events in the active-treatment groups was similar to that in the sham group. Cognitive changes were similar in all 3 treatment groups.\n Our findings provide initial evidence of a beneficial effect of tDCS in fibromyalgia, thus encouraging further trials.", "The authors previously reported that navigation-guided repetitive transcranial magnetic stimulation (rTMS) of the precentral gyrus relieves deafferentation pain. Stimulation parameters were 10 trains of 10-second 5-Hz TMS pulses at 50-second intervals. In the present study, they used various stimulation frequencies and compared efficacies between two types of lesions.\n Patients were divided into two groups: those with a cerebral lesion and those with a noncerebral lesion. The rTMS was applied to all the patients at frequencies of 1, 5, and 10 Hz and as a sham procedure in random order. The effect of rTMS on pain was rated by patients using a visual analog scale.\n The rTMS at frequencies of 5 and 10 Hz, compared with sham stimulation, significantly reduced pain, and the pain reduction continued for 180 minutes. A stimulation frequency of 10 Hz may be more effective than 5 Hz, and at 1 Hz was ineffective. The effect of rTMS at frequencies of 5 and 10 Hz was greater in patients with a noncerebral lesion than those with a cerebral lesion.\n High-frequency (5- or 10-Hz) rTMS of the precentral gyrus can reduce intractable deafferentation pain, but low-frequency stimulation (at 1 Hz) cannot. Patients with a noncerebral lesion are more suitable candidates for high-frequency rTMS of the precentral gyrus.", "Non-invasive unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex induces analgesic effects in focal chronic pain syndromes, probably by modifying central pain modulatory systems. Neuroimaging studies have shown bilateral activation of a large number of structures, including some of those involved in pain processing, suggesting that such stimulation may induce generalized analgesic effects. The goal of this study was to assess the effects of unilateral rTMS of the motor cortex on chronic widespread pain in patients with fibromyalgia. Thirty patients with fibromyalgia syndrome (age: 52.6 +/- 7.9) were randomly assigned, in a double-blind fashion, to two groups, one receiving active rTMS (n = 15) and the other sham stimulation (n = 15), applied to the left primary motor cortex in 10 daily sessions. The primary outcome measure was self-reported average pain intensity over the last 24 h, measured at baseline, daily during the stimulation period and then 15, 30 and 60 days after the first stimulation. Other outcome measures included: sensory and affective pain scores for the McGill pain Questionnaire, quality of life (assessed with the pain interference items of the Brief Pain Inventory and the Fibromyalgia Impact Questionnaire), mood and anxiety (assessed with the Hamilton Depression Rating Scale, the Beck Depression Inventory and the Hospital Anxiety and Depression Scale). We also assessed the effects of rTMS on the pressure pain threshold at tender points ipsi- and contralateral to stimulation. Follow-up data were obtained for all the patients on days 15 and 30 and for 26 patients (13 in each treatment group) on day 60. Active rTMS significantly reduced pain and improved several aspects of quality of life (including fatigue, morning tiredness, general activity, walking and sleep) for up to 2 weeks after treatment had ended. The analgesic effects were observed from the fifth stimulation onwards and were not related to changes in mood or anxiety. The effects of rTMS were more long-lasting for affective than for sensory pain, suggesting differential effects on brain structures involved in pain perception. Only few minor and transient side effects were reported during the stimulation period. Our data indicate that unilateral rTMS of the motor cortex induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia.", "Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation [transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation.\n We performed a preliminary, randomized, sham-controlled, crossover, clinical study in which 8 patients were randomized to receive active tDCS/active TENS (\"tDCS/TENS\" group), active tDCS/sham TENS (\"tDCS\" group), and sham tDCS/sham TENS (\"sham\" group) stimulation. Assessments were performed immediately before and after each condition by a blinded rater.\n The results showed that there was a significant difference in pain reduction across the conditions of stimulation (P=0.006). Post hoc tests showed significant pain reduction as compared with baseline after the tDCS/TENS condition [reduction by 36.5% (+/-10.7), P=0.004] and the tDCS condition [reduction by 15.5% (+/-4.9), P=0.014], but not after sham stimulation (P=0.35). In addition, tDCS/TENS induced greater pain reduction than tDCS (P=0.02).\n The results of this pilot study suggest that the combination of TENS with tDCS has a superior effect compared with tDCS alone.", "Stimulation of the antinociceptive system by noninvasive electrical current from electrodes placed on the head is a renewed method of pain relief.\n We conducted a randomized, double-blind, placebo-controlled study on 20 chronic back pain patients. They were treated with either transcranial electrostimulation (TCES) or an active placebo device. Pain level and serum beta-endorphin levels were measured before and after treatment.\n beta-Endorphin level increased in seven of the ten patients from the treatment group and did not change in eight of ten patients from control group (P = 0.057 between groups). Pain level decreased in eight treated patients and seven control patients (significant decrease for each group, no significant difference between groups).\n Transcranial electrostimulation is a nonpharmacologic method of pain relief accompanied or mediated by beta-endorphin release. The comparable degree of the initial clinical response emphasizes the powerful placebo effect on reported pain not mediated by endorphin release. This preliminary study shows that noninvasive electrical stimulation is a safe treatment with a positive effect on beta-endorphin blood levels.", "To examine the efficacy of transcranial electrical stimulation a non-invasive method of reducing pain.\n A randomized, double-blind, placebo-controlled trial.\n A total of 119 patients with chronic pain.\n Patients were treated with either transcranial electrical stimulation or an active placebo device. Short- and long-term follow-ups were evaluated for treatment efficacy with 4 ordinal scale variables: visual analogue scale (pain level), SLEEP (how often does pain disturb sleep), FREQ (frequency of pain) and MED (frequency of use of medications to relieve pain).\n Pain level decreased significantly in the transcranial electrical stimulation-treated group compared with the active-placebo group 3 weeks after the end of treatment (p = 0.0017 between groups). Other parameters did not demonstrate significant differences. Three months after the end of treatment this effect was maintained and other treatment parameters showed similar improvements.\n Transcranial electrical stimulation is an effective non-invasive method for pain relief. The active placebo device has a powerful effect on reported pain, which diminishes in the long-term. The involvement of possible neural mechanisms is discussed.", "Improvement in sensory detection thresholds was found to be associated with neuropathic pain relief produced by epidural motor cortex stimulation with surgically implanted electrodes.\n To determine the ability of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex to produce similar sensory changes.\n In 46 patients with chronic neuropathic pain of various origins, first-perception thresholds for thermal (cold, warm) and mechanical (vibration, pressure) sensations were quantified in the painful zone and in the painless homologue contralateral territory, before and after rTMS of the motor cortex corresponding to the painful side. Ongoing pain level was also scored before and after rTMS. Three types of rTMS session, performed at 1 Hz or 10 Hz using an active coil, or at 10 Hz using a sham coil, were compared. The relationships between rTMS-induced changes in sensory thresholds and in pain scores were studied.\n Subthreshold rTMS applied at 10 Hz significantly lowered pain scores and thermal sensory thresholds in the painful zone but did not lower mechanical sensory thresholds. Pain relief correlated with post-rTMS improvement of warm sensory thresholds in the painful zone.\n Thermal sensory relays are potentially dysfunctioning in chronic neuropathic pain secondary to sensitisation or deafferentation-induced disinhibition. By acting on these structures, motor cortex stimulation could relieve pain and concomitantly improve innocuous thermal sensory discrimination.", "Double blind, partial crossover.\n To evaluate the analgesic activity of a novel cranial electrostimulus in people with spinal cord injury (SCI).\n Hereward College, a residential centre that provides educational facilities for students with disabilities.\n Subjects with SCI experiencing chronic pain were randomly assigned into two groups, one of which received sham and the other transcranial electrostimulation treatment (TCET) on two occasions daily for four successive days. After a 'wash-out' period of 8 weeks all subjects returned and received the identical stimulus that the treated cohort received on the first arm of the study.\n Pain measurements applied before and after each session indicated that the pain decreased in the treated group to 51% of that reported at the commencement of treatment; reported pain intensity did not decrease significantly in the sham treated subjects. The same (sham) subject group reported experiencing 59% of the pain at the end of the second arm of the study (TCET) as on the first arm (sham). No significant differences were determined between the mood of all subjects estimated before and after each sham or TCET treatment session. The reported analgesic, and combined antidepressant and anxiolytic drug use in subjects receiving TCET on the second arm of the study, was 46% and 53% respectively of the average pre-study drug use. No similar decrease in the use of the drugs was noted in the same subjects after sham treatment on the first arm of the study. Salivary cortisol determinations made prior to and after each sham and treatment session implicated this corticoid in the pain-relieving mode of action of the treatment, but could not be associated with any changes in mood. Subjects receiving TCET had significantly higher urinary 3-methoxy-4-hydroxy-phenylglycol (MHPG) output after the TCET treatment period than sham stimulation, implicating increased central noradrenaline (NA) metabolism in the observed effects.\n The subjects reported less pain during, and immediately after receiving this transcranial treatment, although they were using less medication than when receiving sham treatment.", "To study the efficacy of low-frequency transcranial magnetic stimulation in patients with fibromyalgia and major depression.\n Twenty-eight patients were randomly assigned to receive 20 sessions of real or sham transcranial magnetic stimulation of the right dorsolateral prefrontal cortex. The main stimulation parameters were 15 trains at 110% of the motor threshold for 60 seconds at a frequency of 1 Hz. Blinded external evaluators administered the fibromyalgia scales (FibroFatigue, Likert pain) and the depression scales (Hamilton Depression Rating Scale, Clinical Global Impression) during the study.\n Both treatment groups (real and sham) improved their scores in some of the scales (FibroFatigue and Clinical Global Impression), although there were no differences between them. No improvements were observed in the Likert Pain Scale in either of the groups.\n With the methodology used in this study, patients with fibromyalgia and major depression who received real magnetic stimulation did not present significant differences in symptoms with respect to those who received sham magnetic stimulation.", "Neuropathic pain in patients with MS is frequent and is associated with a great interference with daily life activities. In the present study, we investigated whether anodal transcranial direct current stimulation (tDCS) may be effective in reducing central chronic pain in MS patients. Patients received sham tDCS or real tDCS in a 5-day period of treatment in a randomized, double blind, sham-controlled study. Pain was measured using visual analog scale (VAS) for pain and the short form McGill questionnaire (SF-MPQ). Quality of life was measured using the Multiple Sclerosis Quality of Life-54 scale (MSQoL-54). Depressive symptoms and anxiety were also evaluated as confounding factors using the Beck Depression Inventory (BDI) and VAS for anxiety. Evaluations were performed at baseline, immediately after the end of treatment, and once a week during a 3-week follow-up period. Following anodal but not sham tDCS over the motor cortex, there was a significant pain improvement as assessed by VAS for pain and McGill questionnaire, and of overall quality of life. No depression or anxiety changes were observed. Our results show that anodal tDCS is able to reduce pain-scale scores in MS patients with central chronic pain and that this effect outlasts the period of stimulation, leading to long-lasting clinical effects.\n This article presents a new, noninvasive therapeutic approach to chronic, central neuropathic pain in multiple sclerosis, poorly responsive to current conventional medications. tDCS is known to cause long-lasting changes of neuronal excitability at the site of stimulation and in the connected areas in healthy subjects. This led us to hypothesize that pain decrease may be the result of functional plastic changes in brain structures involved in the pathogenesis of chronic neuropathic pain.\n Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.", "To assess cortical excitability changes in patients with chronic neuropathic pain at baseline and after repetitive transcranial magnetic stimulation (rTMS) of the motor cortex.\n In 22 patients with unilateral hand pain of various neurologic origins and 22 age-matched healthy controls, we studied the following parameters of cortical excitability: motor threshold at rest, motor evoked potential amplitude ratio at two intensities, cortical silent period (CSP), and intracortical inhibition (ICI) and intracortical facilitation. We compared these parameters between healthy subjects and patients at baseline. We also studied excitability changes in the motor cortex corresponding to the painful hand of patients after active or sham rTMS of this cortical region at 1 or 10 Hz.\n At baseline, CSP was shortened for the both hemispheres of patients vs healthy subjects, in correlation with pain score, while ICI was reduced only for the motor cortex corresponding to the painful hand. Regarding rTMS effects, the single significant change was ICI increase in the motor cortex corresponding to the painful hand, after active 10-Hz rTMS, in correlation with pain relief.\n Chronic neuropathic pain was associated with motor cortex disinhibition, suggesting impaired GABAergic neurotransmission related to some aspects of pain or to underlying sensory or motor disturbances. The analgesic effects produced by motor cortex stimulation could result, at least partly, from the restoration of defective intracortical inhibitory processes.", "Drug resistant neurogenic pain can be relieved by repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. This study was designed to assess the influence of pain origin, pain site, and sensory loss on rTMS efficacy.\n Sixty right handed patients were included, suffering from intractable pain secondary to one of the following types of lesion: thalamic stroke, brainstem stroke, spinal cord lesion, brachial plexus lesion, or trigeminal nerve lesion. The pain predominated unilaterally in the face, the upper limb, or the lower limb. The thermal sensory thresholds were measured within the painful zone and were found to be highly or moderately elevated. Finally, the pain level was scored on a visual analogue scale before and after a 20 minute session of \"real\" or \"sham\" 10 Hz rTMS over the side of the motor cortex corresponding to the hand on the painful side, even if the pain was not experienced in the hand itself.\n and discussion: The percentage pain reduction was significantly greater following real than sham rTMS (-22.9% v -7.8%, p = 0.0002), confirming that motor cortex rTMS was able to induce antalgic effects. These effects were significantly influenced by the origin and the site of pain. For pain origin, results were worse in patients with brainstem stroke, whatever the site of pain. This was consistent with a descending modulation within the brainstem, triggered by the motor corticothalamic output. For pain site, better results were obtained for facial pain, although stimulation was targeted on the hand cortical area. Thus, in contrast to implanted stimulation, the target for rTMS procedure in pain control may not be the area corresponding to the painful zone but an adjacent one. Across representation plasticity of cortical areas resulting from deafferentation could explain this discrepancy. Finally, the degree of sensory loss did not interfere with pain origin or pain site regarding rTMS effects.\n Motor cortex rTMS was found to result in a significant but transient relief of chronic pain, influenced by pain origin and pain site. These parameters should be taken into account in any further study of rTMS application in chronic pain control.", "In cranial electrotherapy stimulation (CES), micro-current levels of electrical stimulation are passed across the head via electrodes clipped to the ear lobes. After successful clinical use of CES with fibromyalgia patients in our clinic, it was decided to test these results with a double-blind, placebo-controlled study in which 60 randomly assigned patients were given 3 weeks of 1-hour-daily CES treatments, sham CES treatments, or were held as wait-in-line controls for any placebo effect in the sham-treated patients. Treated patients showed a 28% improvement in tender point scores, and a 27% improvement in self-rated scores of general pain level. The number of subjects rating their quality of sleep as poor dropped from 60% at the beginning of the study to 5%. In addition, there were significant gains in the self-rated feelings of well-being and quality of life, plus gains in six stress-related psychological test measures. No placebo effect was found among the sham-treated controls. A theoretical role of CES in affecting the brain's pain message mechanisms and/or neurohormonal control systems is discussed. It is concluded that CES is as effective as the drug therapies in several trials, with no negative side effects, and deserves further consideration as an additional agent for the treatment of fibromyalgia.", "The precentral gyrus (M1) is a representative target for electrical stimulation therapy of pain. To date, few researchers have investigated whether pain relief is possible by stimulation of cortical areas other than M1. According to recent reports, repetitive transcranial magnetic stimulation (rTMS) can provide an effect similar to that of electrical stimulation. With this in mind, we therefore examined several cortical areas as stimulation targets using a navigation-guided rTMS and compared the effects of the different targets on pain. Twenty patients with intractable deafferentation pain received rTMS of M1, the postcentral gyrus (S1), premotor area (preM), and supplementary motor area (SMA). Each target was stimulated with ten trains of 10-s 5-Hz TMS pulses, with 50-s intervals in between trains. Intensities were adjusted to 90% of resting motor thresholds. Thus, a total of 500 stimuli were applied. Sham stimulations were undertaken at random. The effect of rTMS on pain was rated by patients using a visual analogue scale (VAS) and the short form of the McGill Pain Questionnaire (SF-MPQ). Ten of the 20 patients (50%) indicated that stimulation of M1, but not other areas, provided significant and beneficial pain relief (p<0.01). Results indicated a statistically significant effect lasting for 3 hours after the stimulation of M1 (p<0.05). Stimulation of other targets was not effective. The M1 was the sole target for treating intractable pain with rTMS, in spite of the fact that M1, S1, preM, and SMA are located adjacently.", "Kang BS, Shin HI, Bang MS. Effect of repetitive transcranial magnetic stimulation over the hand motor cortical area on central pain after spinal cord injury.\n To evaluate the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) applied on the hand motor cortical area in patients with spinal cord injury (SCI) who have chronic neuropathic pain at multiple sites in the body, including the lower limbs, trunk, and pelvis.\n Blinded, randomized crossover study.\n University hospital outpatient setting.\n Patients (N=13) with motor complete or incomplete SCI and chronic central pain (11 completed the study).\n rTMS was applied on the hand motor cortical area using a figure-of-eight coil. One thousand stimuli were applied daily on 5 consecutive days. Real and sham rTMS were separated by 12 weeks.\n Numeric rating scale (NRS) for average and worst pain and the Brief Pain Inventory (BPI).\n At 1 week after the end of the rTMS period, the average NRS scores changed from 6.45+/-2.25 to 5.45+/-1.81 with real stimulation and from 6.18+/-1.83 to 5.91+/-2.07 with sham stimulation, and did not differ between treatments. The interference items of the BPI also did not differ between the real and sham rTMS. The effect of time on the NRS score for worst pain was significant with real stimulation but not with sham stimulation.\n The therapeutic efficacy of rTMS was not demonstrated when rTMS was applied to the hand motor cortical area in patients with chronic neuropathic pain at multiple sites in the body, including the lower limbs, trunk, and pelvis. However, the results for worst pain reduction suggest that further studies are required in which rTMS is applied with a more intensive stimulation protocol.", "In complex regional pain syndrome (CRPS) many clinical symptoms suggest involvement of the central nervous system. Neuropathic pain as the leading symptom is often resistant to therapy. In the present study we investigated the analgesic efficiency of repetitive transcranial magnetic simulation (rTMS) applied to the motor cortex contralateral to the CRPS-affected side. Seven out of ten patients reported decreased pain intensities. Pain relief occurred 30 s after stimulation, whereas the maximum effect was found 15 min later. Pain re-intensified increasingly 45 min after rTMS. In contrast, sham rTMS did not alter pain perception. These findings provide evidence that in CRPS I pain perception can be modulated by repetitive motor cortex stimulation.", "Treatments for chronic pain in persons with spinal cord injury (SCI) have been less than effective. Cranial electrotherapy stimulation (CES), a noninvasive technique that delivers a microcurrent to the brain via ear clip electrodes, has been shown to effectively treat several neurological and psychiatric disorders. The present study examined the effects of daily 1-hour active CES or sham CES treatment (randomly assigned) for 21 days on pain intensity and interference with activities in 38 males with SCI. The active CES group (n = 18) reported significantly decreased daily pain intensity compared with the sham CES group (n = 20) (mean change: active CES = -0.73, sham CES = -0.08; p = 0.03). Additionally, the active CES group reported significantly decreased pain interference (-14.6 pre- vs postintervention, p = 0.004) in contrast to the nonsignificant decrease in the sham CES group (-4.7 pre- vs postintervention, p = 0.24). These results suggest that CES can effectively treat chronic pain in persons with SCI.", "nan", "The chronic electrical stimulation of a motor cortical area corresponding to a painful region of the body, by means of surgically-implanted epidural electrodes is a validated therapeutical strategy to control medication-resistant neurogenic pain. Repetitive transcranial magnetic stimulation (rTMS) permits to stimulate non-invasively and precisely the motor cortex. We applied a 20-min session of rTMS of the motor cortex at 10 Hz using a 'real' or a 'sham' coil in a series of 14 patients with intractable pain due to thalamic stroke or trigeminal neuropathy. We studied the effects of rTMS on pain level assessed on a 0-10 visual analogue scale from day 1 to day 12 following the rTMS session. A significant pain decrease was observed up to 8 days after the 'real' rTMS session. This study shows that a transient pain relief can be induced in patients suffering from chronic neurogenic pain during about the week that follows a 20-min session of 10 Hz-rTMS applied over the motor cortex.", "Chronic electrical stimulation of the precentral (motor) cortex using surgically implanted electrodes is performed to treat medication-resistant neurogenic pain. The goal of this placebo-controlled study was to obtain such antalgic effects by means of a non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS). Eighteen patients with intractable neurogenic pain of various origins were included and underwent a 20 min session of either 10 Hz, 0.5 Hz or* sham rTMS over the motor cortex in a random order. A significant decrease in the mean pain level of the series was obtained only after 10 Hz rTMS. This study shows that a transient pain relief can be induced by 10 Hz rTMS of the motor cortex in some patients suffering from chronic neurogenic pain.", "To study the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on central pain in patients with chronic spinal cord injury (SCI).\n Double-blind randomized controlled trial. Mean follow-up period was 4.5 weeks.\n General hospital.\n Twelve paraplegic patients due to thoracic SCI suffering chronic central pain (11 completed the study) who were randomly selected from a list of eligible patients.\n Real or sham 10 daily motor rTMS treatments (500 trains at 5 Hz for 10 s; total of 500 pulses at intensity of 115% of motor threshold) using figure-of-8 coil over the vertex.\n Chronic pain intensity (visual analog scale [VAS], McGill Pain Questionnaire [MPQ]), pain threshold, and level of depression (Beck Depression Inventory).\n Both real and sham TMS induced a similar, significant reduction in VAS scores (P<.001) immediately after each of the 10 treatment sessions and in VAS and MPQ scores after the end of the treatment series. However, only real rTMS conferred a significant increase in heat-pain threshold (4 degrees C, P<.05) by the end of the series. Most important, the reduction in MPQ scores in the real rTMS group continued during the follow-up period. Depression scores were equally reduced in both groups but similar to pain relief, depression continued to improve at follow-up in the real rTMS group.\n Whereas the pain alleviation induced by a single rTMS treatment is probably due to placebo, patients with SCI may benefit from a series of rTMS treatments.", "The modulatory effects of transcranial direct current stimulation (tDCS) appear beneficial for different chronic pain syndromes; however, it is unclear whether this method can be used to treat refractory chronic pelvic pain.\n The objective of this preliminary study was to determine the efficacy and safety of tDCS for the management of refractory chronic pelvic pain.\n Seven patients with chronic pelvic pain having failed standard medical or surgical therapy underwent a crossover, double-blind sham controlled tDCS treatment protocol consisting of 1 mA applied for 20 minutes on two consecutive days with 2 weeks of follow-up symptom recording. Symptoms were recorded using multiple scoring systems, including visual analog scales for different pains, as well as organ-specific symptom scales. Comparison between active and sham treatment was performed by using paired t tests.\n Overall and pelvic pain scores were significantly lower after active compared with sham treatment, as were disability and traumatic stress scores. No patient discontinued the study because of side effects, which were infrequent.\n Active tDCS treatment induces a modest pain reduction in refractory chronic pelvic pain patients as compared with sham tDCS treatment. These results can guide the design and implementation of further studies investigating this method of neuromodulation for the treatment of refractory chronic pelvic pain.", "Fibromyalgia has been recognized as a central pain disorder with evidence of neuroanatomic and neurophysiologic alterations. Previous studies with techniques of noninvasive brain stimulation--transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS)--have shown that these methods are associated with a significant alleviation of fibromyalgia-associated pain and sleep dysfunction. Here we sought to determine whether a longer treatment protocol involving 10 sessions of 2 mA, 20 min tDCS of the left primary motor (M1) or dorsolateral prefrontal cortex (DLPFC) could offer additional, more long-lasting clinical benefits in the management of pain from fibromyalgia. METHODS: Forty-one women with chronic, medically refractory fibromyalgia were randomized to receive 10 daily sessions of M1, DLPFC, or sham tDCS. RESULTS: Our results show that M1 and DLPFC stimulation both display improvements in pain scores (VAS) and quality of life (FIQ) at the end of the treatment protocol, but only M1 stimulation resulted in long-lasting clinical benefits as assessed at 30 and 60 days after the end of treatment. CONCLUSIONS: This study demonstrates the importance of the duration of the treatment period, suggesting that 10 daily sessions of tDCS result in more long lasting outcomes than only five sessions. Furthermore, this study supports the findings of a similarly designed rTMS trial as both induce pain reductions that are equally long-lasting.", "To assess, against placebo, the pain-relieving effects of high-rate repetitive transcranial magnetic stimulation (rTMS) on neuropathic pain.\n Double-blind, randomized, cross-over study of high-rate rTMS against placebo in 28 patients. The effect of a change in coil orientation (posteroanterior vs lateromedial) on different subtypes of neuropathic pain was further tested in a subset of 16 patients. Pain relief was evaluated daily during 1 week.\n High-frequency, posteroanterior rTMS decreased pain scores significantly more than placebo. Posteroanterior rTMS also outmatched placebo in a score combining subjective (pain relief, quality of life) and objective (rescue drug intake) criteria of treatment benefit. Changing the orientation of the coil from posteroanterior to lateromedial did not yield any significant pain relief. The analgesic effects of posteroanterior rTMS lasted for approximately 1 week. The pain-relieving effects were observed exclusively on global scores reflecting the most distressing type of pain in each patient. Conversely, rTMS did not modify specifically any of the pain subscores that were separately tested (ongoing, paroxysmal, stimulus-evoked, or disesthesic pain).\n Posteroanterior repetitive transcranial magnetic stimulation (rTMS) was more effective than both placebo and lateromedial rTMS. When obtained, pain relief was not specific of any particular submodality, but rather reduced the global pain sensation whatever its type. This is in accord with recent models of motor cortex neurostimulation, postulating that its analgesic effects may derive in part from modulation of the affective appraisal of pain, rather than a decrease of its sensory components.", "Stimulating the human cortex using transcranial magnetic stimulation (TMS) temporarily reduces clinical and experimental pain; however, it is unclear which cortical targets are the most effective. The motor cortex has been a popular target for managing neuropathic pain, while the prefrontal cortex has been investigated for an array of nociceptive pain conditions. It is unclear whether the motor cortex is the only effective cortical target for managing neuropathic pain, and no published studies to date have investigated the effects of prefrontal stimulation on neuropathic pain.\n This preliminary pilot trial employed a sham-controlled, within-subject, crossover design to evaluate clinical pain as well as laboratory pain thresholds among four patients with chronic neuropathic pain. Each participant underwent three real and three sham 20-minute sessions of 10 Hz left prefrontal repetitive TMS. Daily pain diaries were collected for 3 weeks before and after each treatment phase along with a battery of self-report pain and mood questionnaires.\n Time-series analysis at the individual patient level indicated that real TMS was associated with significant improvements in average daily pain in 3 of the 4 participants. These effects were independent of changes in mood in two of the participants. At the group level, a decrease of 19% in daily pain on average, pain at its worst, and pain at its least was observed while controlling for changes in mood, activity level and sleep. The effects of real TMS were significantly greater than sham. Real TMS was associated with increases in thermal and mechanical pain thresholds, whereas sham was not. No statistically significant effects were observed across the questionnaire data.\n The prefrontal cortex may be an important TMS cortical target for managing certain types of pain, including certain neuropathic pain syndromes.", "Results of a randomized, double-blind pilot study indicate that transcranial electrotherapy stimulation may be an effective treatment for the temporary reduction of pain in osteoarthritis patients. Presently, the predominant method for pain management is medication. One very different approach is the application of micro- to milliamp current applied to specific areas of the head, resulting in a release of endogenous opioids from pain management regions of the brain. For the pilot study, 64 subjects suffering from osteoarthritis of the knee and/or hip were enrolled. For two weeks prior, then during and after treatment, subject pain was self-assessed using the visual scale (VS). In addition, subjects were globally assessed by a physician. All subjects, device operators and physicians were blinded as to whether subjects were treated with an active or sham device. Data collected from the study indicate both a decrease in VS pain scores and a significant improvement (p = 0.05) in physician assessment in subjects treated with active devices compared to those treated with the sham device.", "This study evaluates the effects of repeated sessions of low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex on central and phantom limb pain.\n Twenty seven patients with central (n=13) and phantom limb (n=14) pain participated in a blind, randomised placebo-controlled study comparing the effect of 1-Hz and 5-Hz rTMS with sham stimulation. Each treatment block consisted of a 5-day baseline phase, a 5-day therapy phase, and an 18-day washout phase. In the therapy phase, 500 stimuli were applied in the particular frequency at about the same time on each day.\n A reduction in pain immediately after stimulation was observed in all therapy groups. This effect was similar for all treatment conditions, including sham stimulation. No significant long-term effects of rTMS on pain intensity or mood were observed.\n At present, rTMS can not be recommended as a standard therapy for central and phantom limb pain.", "Invasive electrical stimulation of the motor cortex has been reported to be of therapeutic value in pain control. We were interested whether noninvasive repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex might also act beneficially. Twelve patients with therapy-resistant chronic pain syndromes (mean age 51.3 +/- 12.6, 6 males) were included in a pilot study. They were treated with rTMS of the corresponding motor cortex area for 20 min (20 Hz, 20 x 2 s trains, intensity 80% of motor threshold) and sham stimulation (sequence-controlled cross-over design). Some of the patients (6/6) had an analgesic effect, but for the whole group, the difference between active and sham stimulation did not reach a level of significance (active rTMS: mean VAS reduction -4.0 +/- 15.6%; sham rTMS: -2.3 +/- 8.8%). Further studies using different rTMS stimulation parameters (duration and frequency of rTMS) or stimulation sites (e.g. anterior cingulate gyrus) are strongly encouraged.\n Copyright 2002 S. Karger AG, Basel", "To assess, using a double-blind procedure, the pain-relieving effects of rTMS against placebo, and their predictive value regarding the efficacy of implanted motor cortex stimulation (MCS).\n Three randomised, double-blinded, 25 min sessions of focal rTMS (1 Hz, 20 Hz and sham) were performed in 12 patients, at 2 weeks intervals. Effects on pain were estimated from daily scores across 5 days before, and 6 days after each session. Analgesic effects were correlated with those of subsequent implanted motor cortex stimulation (MCS).\n Immediately after the stimulating session, pain scores were similarly decreased by all rTMS modalities. Conversely, during the following week, 1 Hz stimulation provided significantly less analgesia than 20 Hz and placebo, and was pro-algesic in some patients. Placebo and 20 Hz rTMS were effective on different patients, and only 20 Hz rTMS predicted the efficacy of subsequent MCS, with no false positives.\n While 1Hz rTMS should not be used with analgesic purposes, high-frequency rTMS may become useful to select candidates for MCS. Placebo effects are powerful and should be controlled for. Immediate results after a single rTMS session are misleading.\n Defining rTMS parameters is a crucial step before proposing rTMS as predictive test of SCM efficacy in clinical practice." ]

[ "12457784" ]

[ "Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial." ]

[ "Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke.\n We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat.\n Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability.\n Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people." ]

[ "8310510", "16371925", "8479129", "21699484", "15086477", "8420065", "11072938", "12600912", "12124559" ]

[ "The beneficial effect of human recombinant superoxide dismutase on acute and chronic rejection events in recipients of cadaveric renal transplants.", "Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadaveric renal transplantation: a randomized placebo controlled trial.", "A multivitamin infusion prevents lipid peroxidation and improves transplantation performance.", "Bardoxolone methyl and kidney function in CKD with type 2 diabetes.", "Effects of vitamin E on cardiovascular outcomes in people with mild-to-moderate renal insufficiency: results of the HOPE study.", "A randomized double-blind trial of the use of human recombinant superoxide dismutase in renal transplantation.", "Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial.", "The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: a randomized, controlled trial.", "Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation?" ]

[ "In a prospective randomized double-blind placebo-controlled trial, the effect of rh-SOD, given in a dose of 200 mg intravenously during surgery to cyclosporine-treated recipients of cadaveric renal allografts, on both acute and chronic rejection events as well as patient and graft survival was investigated by analyzing the patients' charts retrospectively. The results obtained show that rh-SOD exerts a beneficial effect on acute rejection events as indicated by a significant reduction of (1) first acute rejection episodes from 33.3% in controls to 18.5%, as well as (2) early irreversible acute rejection from 12.5% in controls to 3.7%. With regard to long-term results, there was a significant improvement of the actual 4-year graft survival rate in rh-SOD-treated patients to 74% (with a projected half-life of 15 years) compared with 52% in controls (with an extrapolated half-life of 5 years). The beneficial effect of rh-SOD observed in this trial is not fully understood, although one can assume that the effect is related to its antioxidant action on ischemia/reperfusion injury of the renal allograft, thereby potentially reducing the immunogenicity of the graft. In addition and in accordance with the \"response-to-injury hypothesis\" in the pathogenesis of general atherosclerosis, rh-SOD has the potential to mitigate free radical-mediated reperfusion injury-induced acute endothelial cell damage that potentially may contribute to the process of chronic obliterative rejection arteriosclerosis.", "The bioflavonoids quercetin and curcumin are renoprotective natural antioxidants. We wished to examine their effects on early graft function (EF).\n Between September 2002 and August 2004, 43 dialysis dependent cadaveric kidney recipients were enrolled into a study using Oxy-Q which contains 480 mg of curcumin and 20 mg of quercetin, started after surgery and taken for 1 month. They were randomized into three groups: control (placebo), low dose (one capsule, one placebo) and high dose (two capsules). Delayed graft function (DGF) was defined as first week dialysis need and slow function (SGF) as Cr >2.5 mg/dl by day 10. Category variables were compared by chi squared and continuous variables by Kruskal-Wallis.\n There were four withdrawals: one by patient choice and three for urine leak. The control group had 2/14 patients with DGF vs. none in either treatment group. Incidence of EF was control 43%, low dose 71% and high dose 93% (P=0.013). Serum creatinine was significantly lower at 2 days (control 7.6+/-2.1, low 5.4+/-0.6, high 3.96+/-.35 P=0.0001) and 30 days (control 1.82+/-.16, low 1.65+/-.09, high 1.33 +/-.1, P=0.03). Acute rejection incidence within 6 months was control 14.3%, low dose 14.3% and high dose 0%. Tremor was detected in 13% of high dose patients vs. 46% of others. Urinary HO-1 was higher in bioflavonoid groups.\n Bioflavonoid therapy improved early graft function. Acute rejection and neurotoxicity were lowest in the high dose group. These bioflavonoids improve early outcomes in cadaveric renal transplantation, possibly through HO-1 induction.", "The objective of this study was to test the hypothesis that ischemia reperfusion damage in kidney transplantation is associated with lipid peroxidation and that inhibition of lipid peroxidation by antioxidants improves the function of the transplanted kidney. Lipid peroxidation was assessed by measuring the plasma malonaldehyde content (as thiobarbituric acid reaction product) with high-performance liquid chromatography. Kidney function was assessed by plasma creatinine and creatinine clearance. Thirty patients of an ongoing series were randomly selected into two groups, with 14 controls and 16 patients in the antioxidant therapy group. Therapy consisted of two ampoules of Omnibionta (which contains vitamins C, E, A and B complex) diluted in 500 ml physiological sodium chloride, which was infused intravenously prior to reperfusion onset. No significant differences existed for the age of the patients in the control (43.00 +/- 9.86 years) and the therapy group (41.56 +/- 14.14 years) nor in the kidney preservation time, which was 24.12 +/- 8.73 and 18.43 +/- 9.97 hours in the control and therapy group, respectively. The controls showed a transient increase of plasma lipid peroxides as measured by malonaldehyde with a peak one hour after onset of reperfusion. Compared to the baseline value of 0.74 +/- 0.26 (mean +/- SD) the one hour malonaldehyde value increased to 1.46 +/- 0.22 nmol/ml (P < 0.001). In the therapy group the plasma malonaldehyde level did not increase, but slightly decreased by about 20% compared to the baseline value. The difference of plasma malonaldehyde between the two groups one hour after reperfusion onset was highly significant (P > 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)", "Chronic kidney disease (CKD) associated with type 2 diabetes is the leading cause of kidney failure, with both inflammation and oxidative stress contributing to disease progression. Bardoxolone methyl, an oral antioxidant inflammation modulator, has shown efficacy in patients with CKD and type 2 diabetes in short-term studies, but longer-term effects and dose response have not been determined.\n In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned 227 adults with CKD (defined as an estimated glomerular filtration rate [GFR] of 20 to 45 ml per minute per 1.73 m(2) of body-surface area) in a 1:1:1:1 ratio to receive placebo or bardoxolone methyl at a target dose of 25, 75, or 150 mg once daily. The primary outcome was the change from baseline in the estimated GFR with bardoxolone methyl, as compared with placebo, at 24 weeks; a secondary outcome was the change at 52 weeks.\n Patients receiving bardoxolone methyl had significant increases in the mean (±SD) estimated GFR, as compared with placebo, at 24 weeks (with between-group differences per minute per 1.73 m(2) of 8.2±1.5 ml in the 25-mg group, 11.4±1.5 ml in the 75-mg group, and 10.4±1.5 ml in the 150-mg group; P<0.001). The increases were maintained through week 52, with significant differences per minute per 1.73 m(2) of 5.8±1.8 ml, 10.5±1.8 ml, and 9.3±1.9 ml, respectively. Muscle spasms, the most frequent adverse event in the bardoxolone methyl groups, were generally mild and dose-related. Hypomagnesemia, mild increases in alanine aminotransferase levels, and gastrointestinal effects were more common among patients receiving bardoxolone methyl.\n Bardoxolone methyl was associated with improvement in the estimated GFR in patients with advanced CKD and type 2 diabetes at 24 weeks. The improvement persisted at 52 weeks, suggesting that bardoxolone methyl may have promise for the treatment of CKD. (Funded by Reata Pharmaceuticals; BEAM ClinicalTrials.gov number, NCT00811889.).", "A controlled trial reported cardiovascular benefits of vitamin E in terminal renal insufficiency. There are no data for renal insufficiency before the stage of terminal renal failure. We evaluated effects of vitamin E supplementation on cardiovascular and renal outcomes in 993 people with a serum creatinine > or =1.4 to 2.3 mg/dL.\n Post-hoc analysis of a randomized trial that compared treatment with natural source vitamin E (400 IU/day) to placebo in 9541 people, 993 of which had renal insufficiency. Participants had either known cardiovascular disease or diabetes and at least one additional coronary risk factor. Exclusion criteria included a serum creatinine > 2.3 mg/dL and dipstick-positive proteinuria. The primary study outcome after an average of 4.5 years was the composite of myocardial infarction, stroke, or cardiovascular death. Secondary outcomes included revascularizations, total mortality, and clinical proteinuria.\n In renal insufficiency, vitamin E supplementation had a neutral effect on the primary study outcome, on each component of the composite primary outcome, and on all secondary outcomes. Two hundred twenty-four primary outcomes, 23% of the vitamin E group and 22.1% of the placebo group, relative risk 1.03 (95% CI, 0.79-1.34; P= 0.82), were observed, and 585 secondary outcomes, including death in 17% and 18.8% of the vitamin E and placebo groups, respectively (RR 0.88, 95% CI, 0.66-1.18; P= 0.40). There was no effect of vitamin E on progression of proteinuria.\n In people with mild-to-moderate renal insufficiency at high cardiovascular risk, vitamin E at a dose of 400 IU/day had no apparent effect on cardiovascular outcomes.", "Oxygen free radical generation has been implicated as a possible mediator of the reperfusion injury postulated to occur following revascularization of the cold preserved and transplanted kidney. The superoxide radical (O2-) scavenger, superoxide dismutase, from bovine or recombinant (rh-SOD) sources, may ameliorate oxygen-free-radical mediated reperfusion injury of transplanted kidneys. To test this hypothesis, we performed a prospective, randomized, double-blind trial of the use of human rh-SOD in renal transplantation at three participating centers. Half of a 20 mg/kg solution of rh-SOD or placebo was administered as a bolus intravenous injection immediately prior to renal allograft reperfusion and the remainder as a peripheral intravenous infusion for 1 hr thereafter. Posttransplant renal function was determined using 99Tc-DTPA clearance to measure glomerular filtration rate at 48 +/- 24 hr and day 6 post-transplant. A two-tailed t test was used for pooled data, and analysis of variance was used to evaluate between center differences in outcome. One hundred and sixteen patients (58 rh-SOD and 58 placebo) were entered into the study. No adverse reactions to rh-SOD or placebo were noted. No differences were noted between rh-SOD and placebo groups with regard to GFR at 48 hr, serum creatinine or creatinine clearance at day 6, or percentage of patients with GFR < or = 10 ml/min or < or = 5 ml/min at 48 hr. The data did not vary when analyzed by center or in aggregate form, and no correlation was noted between storage time and GFR in either group. We conclude that data from this trial provide little basis for the use of rh-SOD as described to ameliorate reperfusion injury in transplanted kidneys.", "Excess cardiovascular mortality has been documented in chronic haemodialysis patients. Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without, suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis. We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease.\n Haemodialysis patients with pre-existing cardiovascular disease (n=196) aged 40-75 years at baseline from six dialysis centres were enrolled and randomised to receive 800 IU/day vitamin E or matching placebo. Patients were followed for a median 519 days. The primary endpoint was a composite variable consisting of: myocardial infarction (fatal and non-fatal), ischaemic stroke, peripheral vascular disease (excluding the arteriovenous fistula), and unstable angina. Secondary outcomes included each of the component outcomes, total mortality, and cardiovascular-disease mortality.\n A total of 15 (16%) of the 97 patients assigned to vitamin E and 33 (33%) of the 99 patients assigned to placebo had a primary endpoint (relative risk 0.46 [95% CI 0.27-0.78], p=0.014). Five (5.1%) patients assigned to vitamin E and 17 (17.2%) patients assigned to placebo had myocardial infarction (0.3 [0.11-0.78], p=0.016). No significant differences in other secondary endpoints, cardiovascular disease, or total mortality were detected.\n In haemodialysis patients with prevalent cardiovascular disease, supplementation with 800 IU/day vitamin E reduces composite cardiovascular disease endpoints and myocardial infarction.", "Patients with end-stage renal failure have increased oxidative stress and show elevated cardiovascular mortality. Whether increased cardiovascular events can be prevented by the administration of antioxidants is unknown.\n We evaluated the effects of acetylcysteine, a thiol-containing antioxidant, on cardiovascular events in patients undergoing hemodialysis. A prospective, randomized, placebo-controlled trial was conducted between October 1, 1999, and September 30, 2001, in 134 patients (76 male and 58 female) with a mean age of 62+/-16 years (mean+/-SD) who had been undergoing maintenance hemodialysis for a minimum of 3 months 3 times weekly in an ambulatory center. Median (range) follow-up was 14.5 (1 to 24) months. Patients were randomly assigned either to receive acetylcysteine (600 mg BID) or placebo. The primary end point was a composite variable consisting of cardiac events including fatal and nonfatal myocardial infarction, cardiovascular disease death, need for coronary angioplasty or coronary bypass surgery, ischemic stroke, peripheral vascular disease with amputation, or need for angioplasty. Secondary end points included each of the component outcomes, total mortality, and cardiovascular mortality. A total of 18 (28%) of the 64 hemodialysis patients assigned to acetylcysteine group and 33 (47%) of the 70 hemodialysis patients assigned to control group had a primary end point (relative risk, 0.60 [95% CI, 0.38 to 0.95], P=0.03). No significant differences in secondary end points or total mortality were detected.\n In hemodialysis patients, treatment with acetylcysteine (600 mg BID) reduces composite cardiovascular end points.", "Renal failure after lower torso ischemia is a serious problem, partly caused by hypotension and indirect reperfusion injury. This injury is partly due to the formation of oxygen free radicals by activated neutrophils. This injury results in albuminuria and renal function impairment. There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion.\n In this prospective randomised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair. The patients received either standard treatment (n=22) or standard treatment with additional antioxidants perioperatively (Allopurinol, vitamin E and C, N-acetylcysteine and mannitol). For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance.\n Despite significantly increased serum total antioxidant capacity, the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine. There was however a significantly higher creatinine clearance in this group at day 2.\n The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy." ]

[ "3554492", "9407981", "8969668", "12548410", "10678027", "1991422" ]

[ "A randomized trial of fistulotomy in perianal abscess.", "Randomized controlled trial of primary fistulotomy with drainage alone for perianal abscesses.", "Prospective randomized trial of drainage alone vs. drainage and fistulotomy for acute perianal abscesses with proven internal opening.", "Randomized clinical trial comparing simple drainage of anorectal abscess with and without fistula track treatment.", "[Primary curative incision in the treatment of perianorectal abscess].", "Treatment of anorectal abscess with or without primary fistulectomy. Results of a prospective randomized trial." ]

[ "In a randomized trial we compared the treatment of perianal abscess by incision only (18 patients) with that by incision followed by fistulotomy 3 days later (20 patients). All patients were observed for 12 months. There were no differences between the two groups with regard to recurrent abscess/fistula, but the fistulotomy group had a statistically significantly higher prevalence of flatus incontinence. Further, fistulotomy was followed by significantly longer duration of hospitalization and by delayed healing. We recommend that fistulotomy is used only in patients with recurrent abscess.", "Primary fistulotomy may be advantageous for perianal abscesses because unlike ischiorectal abscesses, fistulas are more commonly found and can be laid open with full preservation of the external anal sphincters. Therefore, a randomized, controlled trial was conducted to compare primary fistulotomy with incision and drainage alone, specifically for perianal abscesses.\n Fifty-two consecutive patients (43 males; mean age, 40 (standard error of mean, 2) years) with perianal abscesses were randomized to treatment by either incision and drainage (controls; N = 28) or fistulotomy (N = 24). Patients were followed up clinically for a mean of 15.5 (standard error of the mean, 0.7) months. Anorectal manometry was also performed before, six weeks, and three months after surgery.\n Persistent fistulas developing after surgery were significantly more common after incision and drainage (N = 7; 25 percent) than after fistulotomy (N = 0; P = 0.009). One patient in each group was also found to have a residual abscess, which required repeat drainage. All patients remained fully continent. The anal pressures after incision and drainage and fistulotomy were not significantly different. Operative time, hospital stay, and time for the wound to heal completely were the same in both groups.\n Primary fistulotomy at the time of drainage for perianal abscesses results in fewer persistent fistulas and no added risk of fecal incontinence.", "Incision and drainage (I & D) with concurrent or delayed fistulotomy is the usual treatment for abscess-fistula with a demonstrated internal opening. We compared incision and drainage alone vs. with concurrent fistulotomy for perianal abscesses with a demonstrated internal opening.\n Consecutive patients with acute perianal abscesses and a demonstrated internal opening were prospectively randomized into either the I & D group or drainage with concurrent fistulotomy group. They were followed up at one month, three months, and one year.\n The I & D group had 21 patients, and the fistulotomy group had 24 patients. Thirteen patients had low intersphincteric abscess-fistula, and seven had low transsphincteric fistulas in the I & D group. The fistulotomy group had 9 intersphincteric abscess-fistula compared with 14 low transsphincteric ones. Median duration of surgery, hospital stay, and continence at final follow-up were the same in the two groups. Three had recurrent abscess-fistula in the I & D group compared with none in the fistulotomy group (P = 0.09).\n I & D alone for acute anal abscess-fistula with demonstrated internal opening showed a tendency to recurrence that did not reach a statistically significant difference compared with concurrent fistulotomy. I & D, therefore, puts only a few patients at risk for recurrence.", "Anal abscess is a frequent acute proctological disorder and whether the underlying fistula should be treated at the same time when the abscess is drained remains controversial. We examined indications for drainage alone versus drainage plus fistulotomy in terms of recurrence and continence.\n We carried out a randomized prospective study of 200 consecutive patients with anal abscess. One group received drainage alone, while in the other group drainage plus fistulotomy was performed when a subcutaneous-mucosa, low transsphincteral, or intersphincteral fistula was found. Delayed progressive fistulotomy with suture threads was performed in cases of high transsphincteric or suprasphincteric fistula.\n The internal opening of the fistula track was found in 83% of the patients. The recurrence rate was related to the surgical technique employed: 29% in the group with drainage alone and 5% in the group for which treatment of the fistula track was attempted. The incontinence rate was also related to the surgical option. In those receiving drainage and treatment of the fistula track incontinence was restricted mostly to patients with delayed fistulotomy (36.7%), compared to 2.8% of patients when simple fistulotomy was performed. There was no incontinence in the drainage alone group.\n Drainage of anal abscess with fistulotomy can be safely performed in cases of subcutaneous, intersphincteral, or low transsphincteral fistulae with a minimal recurrence rate. However, drainage alone and posterior treatment of the fistula track is recommended for high transsphincteral or suprasphincteral fistulae.", "More than 50% of the patients with perianorectal abscess treated with traditional incisional drainage will lead to fistula formation postoperatively. We present a procedure of primary curative incision for treatment with perianorectal abscess without fistula formation. The result of primary curative incision in comparison with traditional incisional drainage in a randomized control study showed that the incidence of postoperative fistula formation and recurrent abscess was 2.56% in the former and 56.25% in the latter. The key points of the procedure were discussed in detail and the causes and prevention of the disease occurred after injection of sclerotic drugs for hemorrhoids were also discussed.", "To determine whether primary fistulectomy should be performed or not at the time of incision and drainage, a prospective, randomized study in 70 patients with anorectal abscess was conducted. Thirty-six patients underwent incision, drainage and fistulectomy with primary partial internal spincterectomy (group I), whereas in 34 patients anorectal abscess was treated by incision and drainage alone (group II). After a median follow-up of 42.5 months, the combined recurrence or persistence rate was 2.9 percent in group I and 40.6 percent in group II (P less than 0.0003, log-rank test). Recurrent abscesses or persistent fistulas were treated by secondary partial internal sphincterectomy. Comparing anal continence before and 1 year after definite treatment, we found increased anal function disturbances in 39.4 percent of the patients in group I and in 21.4 percent of the patients in group II (P less than 0.106, Fisher-exact test). The combined recurrence or persistence rate of 40.6 percent indicates that more than half of the patients with anorectal abscess will have no further problems after simple incision and drainage. This finding, as well as the increased anal function disturbances after partial internal sphincterectomy (either primary or secondary) are the main reasons to reserve fistulectomy as a second stage procedure if necessary." ]

[ "21270788", "18575629" ]

[ "Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic.", "A vaccine against nicotine for smoking cessation: a randomized controlled trial." ]

[ "NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.", "Tobacco dependence is the leading cause of preventable death and disabilities worldwide and nicotine is the main substance responsible for the addiction to tobacco. A vaccine against nicotine was tested in a 6-month randomized, double blind phase II smoking cessation study in 341 smokers with a subsequent 6-month follow-up period.\n 229 subjects were randomized to receive five intramuscular injections of the nicotine vaccine and 112 to receive placebo at monthly intervals. All subjects received individual behavioral smoking cessation counseling. The vaccine was safe, generally well tolerated and highly immunogenic, inducing a 100% antibody responder rate after the first injection. Point prevalence of abstinence at month 2 showed a statistically significant difference between subjects treated with Nicotine-Qbeta (47.2%) and placebo (35.1%) (P = 0.036), but continuous abstinence between months 2 and 6 was not significantly different. However, in subgroup analysis of the per-protocol population, the third of subjects with highest antibody levels showed higher continuous abstinence from month 2 until month 6 (56.6%) than placebo treated participants (31.3%) (OR 2.9; P = 0.004) while medium and low antibody levels did not increase abstinence rates. After 12 month, the difference in continuous abstinence rate between subjects on placebo and those with high antibody response was maintained (difference 20.2%, P = 0.012).\n Whereas Nicotine-Qbeta did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction.\n Swiss Medical Registry 2003DR2327; ClinicalTrials.gov NCT00369616." ]

[ "2657423", "9722255", "8323356", "7752005", "7700763", "9545359" ]

[ "A controlled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia.", "Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.", "Dexamethasone treatment in preterm infants at risk for bronchopulmonary dysplasia.", "Effect of pulse dexamethasone therapy on the incidence and severity of chronic lung disease in the very low birth weight infant.", "Effects of early dexamethasone therapy on pulmonary mechanics and chronic lung disease in very low birth weight infants: a randomized, controlled trial.", "A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants." ]

[ "We evaluated the use of dexamethasone in preterm infants to decrease morbidity associated with bronchopulmonary dysplasia in a randomized, double-blind, placebo-controlled trial. Thirty-six preterm infants (birth weight, less than or equal to 1250 g and gestational age, less than or equal to 30 weeks) who were dependent on oxygen and mechanical ventilation at two weeks of age received a 42-day course of dexamethasone (n = 13), an 18-day course of dexamethasone (n = 12), or saline placebo (n = 11). The starting dose of dexamethasone was 0.5 mg per kilogram of body weight per day, and it was progressively lowered during the period of administration. Infants in the 42-day dexamethasone group, but not those in the 18-day group, were weaned from mechanical ventilation significantly faster than control infants (medians 29, 73, and 84 days, respectively; P less than 0.05), and from supplemental oxygen (medians 65, 190, and 136 days, respectively; P less than 0.05). No clinical complications of steroid administration were noted. Follow-up of all 23 survivors at 6 and 15 months of age showed good outcome (normal neurologic examinations and Bayley Developmental Indexes greater than or equal to 84) in 7 of the 9 infants in the 42-day dexamethasone group, but in only 2 of the 9 infants in the 18-day dexamethasone group and 2 of the 5 in the placebo group (P less than 0.05). We conclude that dexamethasone therapy for 42 days improves pulmonary and neurodevelopmental outcome in very-low-birth-weight infants at high risk for bronchopulmonary dysplasia.", "In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.", "A randomised double blind placebo controlled study was conducted to determine whether a one week course of dexamethasone could reduce the severity of bronchopulmonary dysplasia in preterm infants without compromising their adrenal function. Forty one infants with a mean birth weight of 880 g and a gestational age of 27 weeks who were ventilator dependent at 10 days of age were enrolled. At the age of 28 days pulmonary outcome was significantly better in the girls treated with dexamethasone but not in all infants. There was no difference between the groups in the long term outcome, except for a shorter duration of supplemental oxygen in dexamethasone treated female infants. After the one week dexamethasone treatment there was a significant but short lived suppression of the basal cortisol concentrations and the adrenal response to corticotrophin (ACTH). No serious side effects were observed. It is concluded that early one week dexamethasone treatment improves short term pulmonary outcome in premature infants, but there is no clear evidence of long term benefits.", "We conducted a prospective, randomized, double-blind trial to assess the efficacy and safety of pulse doses of dexamethasone on survival without supplemental oxygen in very low birth weight infants at high risk of having chronic lung disease. Seventy-eight infants with birth weights < or = 1500 gm who were ventilator dependent at 7 days of postnatal age were randomly assigned to receive pulse doses of dexamethasone, 0.5 mg/kg per day, divided twice daily (n = 39), or an equivalent volume of saline solution placebo (n = 39), for 3 days at 10-day intervals until they no longer required supplemental oxygen or assisted ventilation, or reached 36 weeks of postmenstrual age. At study entry, the groups did not differ by birth weight, gestational age, or severity of lung disease. At 36 weeks of postmenstrual age, there was both a significant increase in survival rates without oxygen supplementation (p = 0.03) and a significant decrease in the incidence of chronic lung disease (p = 0.047) in the group that received pulse therapy. Supplemental oxygen requirements were less throughout the study period in the group that received repeated pulse doses of dexamethasone (p = 0.013). The total numbers of deaths and the durations of supplemental oxygen, ventilator support, and hospital stay did not differ between groups. Recorded side effects in the pulse therapy group were minimal and included an increase in the use of insulin therapy for hyperglycemia (p < 0.05). We conclude that in this population of very low birth weight infants, treatment with pulse doses of dexamethasone resulted in improvement in pulmonary outcome without clinically significant side effects.", "To determine the changes in pulmonary mechanics before and during early dexamethasone therapy, and to evaluate the effect of dexamethasone on the duration of mechanical ventilation in very low birth weight (VLBW) ventilator-dependent infants at risk for chronic lung disease (CLD).\n A prospective randomized trial was conducted. Forty-three patients (birth weight 600 to 1500 g, gestational age 24 to 32 weeks) who failed to be weaned from the respirator at 7 to 14 days of age were enrolled; 23 infants received a 7-day course of dexamethasone (0.5 mg/kg/day intravenously for 3 days, 0.25 mg/kg/day for 3 days, and 0.1 mg/kg/day for 1 day), and 20 patients were in the control group. At similar mean airway pressure (MAP) and fractional inspired oxygen concentration (FiO2), respiratory system mechanics were measured before and on days 2, 5, and 7 of the study. Airway pressure, flow and tidal volume (VT) were recorded and only mechanical breaths were analyzed. Respiratory compliance (Crs) and respiratory resistance (Rrs) were calculated by two factor least mean square analysis.\n Eighty-three percent of infants in the dexamethasone group and 90% in the control group received surfactant in the first 24 hours of life. There was a significant increase in Crs and VT in the dexamethasone group as compared with the control group (P < .001). No major changes in Rrs were observed. Dexamethasone therapy significantly decreased FiO2 and MAP P < .001) and facilitated successful weaning from mechanical ventilation. In addition to a shorter duration of mechanical ventilation (P < .01), the occurrence of CLD (FiO2 > 0.21 at 36 weeks of corrected gestational age, chest radiograph changes) was significantly decreased in the dexamethasone group (P < .01). Except for a transient increase in blood pressure and serum glucose, there were no significant differences in infection rates, intraventricular hemorrhage, or retinopathy of prematurity. Thirteen patients in the control group received dexamethasone at a later age.\n Our findings indicate that: 1) early dexamethasone therapy in VLBW infants markedly improves respiratory compliance and tidal volume, reduces FiO2 and MAP requirements, and facilitates extubation in these infants; 2) early dexamethasone therapy reduces the duration of mechanical ventilation and decreases CLD (at 28 days and 36 weeks) in a population of VLBW infants largely treated with surfactant.", "Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown.\n We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 g) who had respiratory index scores (mean airway pressure x the fraction of inspired oxygen) of 52.4 at two weeks of age. One hundred eighty-two infants received dexamethasone for two weeks followed by placebo for two weeks, and 189 infants received placebo for two weeks followed by either dexamethasone (those with a respiratory-index score of > or =2.4 on treatment day 14) or additional placebo for two weeks. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose was then tapered.\n The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks' postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P< 0.001) in both groups.\n Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of ages." ]

[ "16462503", "17785709", "9414057", "15022300", "3966583", "16488348", "11747326", "17438709", "17661342", "12096294", "16135471", "17066964", "11742045", "1602030", "12096292", "18543381", "7235853", "16618589", "11343530", "10474848", "10833696", "8564938", "12790259", "10939175", "12433015" ]

[ "Will improvement in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer?", "Randomized controlled trial of yoga among a multiethnic sample of breast cancer patients: effects on quality of life.", "A pain education program for chronic cancer pain patients: follow-up results from a randomized controlled trial.", "A randomized clinical trial of energy conservation for patients with cancer-related fatigue.", "Psychotherapy during radiotherapy: effects on emotional and physical distress.", "Supportive intervention for fatigue in patients undergoing chemotherapy: a randomized controlled trial.", "Evaluation of nurse-led follow up for patients undergoing pelvic radiotherapy.", "\"Between Men\": a psychosocial rehabilitation programme for men with prostate cancer.", "A randomized controlled trial to evaluate the effectiveness of a brief, behaviorally oriented intervention for cancer-related fatigue.", "Intervention to improve psychological functioning for newly diagnosed patients with cancer.", "Randomized controlled trial of an educational intervention for managing fatigue in women receiving adjuvant chemotherapy for early-stage breast cancer.", "Randomized clinical trial on cognitive therapy for depression in women with metastatic breast cancer: psychological and immunological effects.", "The effect of group psychosocial support on survival in metastatic breast cancer.", "Relaxation therapy as an adjunct in radiation oncology.", "Pain and fatigue management: results of a nursing randomized clinical trial.", "Medical Qigong for cancer patients: pilot study of impact on quality of life, side effects of treatment and inflammation.", "Group support for patients with metastatic cancer. A randomized outcome study.", "Nursing education as an intervention to decrease fatigue perception in oncology patients.", "Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial.", "A group cognitive behaviour therapy programme with metastatic breast cancer patients.", "Telephone therapy for patients with breast cancer.", "A psychoeducational nursing intervention to enhance coping and affective state in newly diagnosed malignant melanoma patients.", "Short-term effects of telephone therapy for breast cancer patients.", "The effectiveness of the comprehensive coping strategy program on clinical outcomes in breast cancer autologous bone marrow transplantation.", "A pilot study of the effects of expressive writing on psychological and behavioral adjustment in patients enrolled in a Phase II trial of vaccine therapy for metastatic renal cell carcinoma." ]

[ "Fatigue has a significant impact on the quality of life (QOL) of cancer patients. Recent research has suggested that physical activity can reduce fatigue in patients receiving active cancer treatment. In this project, we examined the impact that participation in a randomized controlled trial of a multidisciplinary intervention designed to impact overall QOL had on fatigue for advanced cancer patients actively receiving treatment.\n Patients with newly diagnosed cancer were randomly assigned to an 8-session structured multidisciplinary intervention or a standard-care arm at the beginning of their course of radiotherapy (RT) designed to impact QOL. Ninety-minute sessions were led by either a psychiatrist or psychologist, collaborating with a nurse, physical therapist, chaplain, or social worker, depending on the session's theme. The fatigue assessments used in this trial included the Linear Analogue Self Assessment (LASA), the Profile of Mood States (POMS), Spielberger's State-Trait Anxiety Inventory (STAI), and the Symptom Distress Scale (SDS).\n There were 115 participants enrolled and the 2 randomization arms were well balanced in terms of baseline characteristics and treatment received except for increased commuting distance for the patients in the intervention arm (P = 0.042). Most of scores indicated less fatigue (higher score) in the standard treatment group, but there were no statistically significant differences found at baseline and weeks 4, 8, and 27 except for SDS at week 8 (P = 0.018) with less patients reporting significant fatigue in the standard treatment arm. For the entire participant population, fatigue levels initially worsened with radiotherapy, stabilized at week 8, and returned to baseline by week 27. Disease site, chemotherapy use, and radiotherapy dose did not have a significant impact on fatigue levels.\n Radiotherapy initially caused a worsening of fatigue but with time fatigue levels returned to baseline. Clinically, this structured multidisciplinary intervention had no impact on fatigue, and there was the suggestion the multiple sessions may have contributed to worse fatigue during active cancer treatment.", "This study examines the impact of yoga, including physical poses, breathing, and meditation exercises, on quality of life (QOL), fatigue, distressed mood, and spiritual well-being among a multiethnic sample of breast cancer patients.\n One hundred twenty-eight patients (42% African American, 31% Hispanic) recruited from an urban cancer center were randomly assigned (2:1 ratio) to a 12-week yoga intervention (n = 84) or a 12-week waitlist control group (n = 44). Changes in QOL (eg, Functional Assessment of Cancer Therapy) from before random assignment (T1) to the 3-month follow-up (T3) were examined; predictors of adherence were also assessed. Nearly half of all patients were receiving medical treatment.\n Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates (P < .0001). Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL (P < .008), emotional well-being (P < .015), social well-being (P < .004), spiritual well-being (P < .009), and distressed mood (P < .031). Sixty-nine percent of intervention participants attended classes (mean number of classes attended by active class participants = 7.00 +/- 3.80), with lower adherence associated with increased fatigue (P < .001), radiotherapy (P < .0001), younger age (P < .008), and no antiestrogen therapy (P < .02).\n Despite limited adherence, this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors. Among patients not receiving chemotherapy, yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL.", "The effectiveness of a Pain Education Program in cancer patients with chronic pain offered by nurses was investigated in a randomized controlled clinical trial. A multi-method approach was used in which verbal instruction, written material, an audio cassette tape, and the use of a pain diary were combined to inform and instruct patients about pain and pain management. The Pain Education Program was tailored to the needs of the individual patient and consisted of three elements: (1) educating patients about the basic principles regarding pain and pain management; (2) instructing patients how to report their pain in a pain diary; and (3) instructing patients how to communicate about pain and how to contact health care providers. Following pretesting in 313 patients, patients who needed district nursing and who did not need district nursing at home were randomly assigned to a control or intervention group. Intervention group patients received the Pain Education Program in the hospital, and 3 and 7 days postdischarge by telephone; this was done by nurses who were specially trained as pain counselors. Follow-up assessments were at 2, 4 and 8 weeks postdischarge. Results of the pretest showed that many patients lacked knowledge about pain and pain management. The majority of pain topics had to be discussed. The Pain Education Program proved to be feasible: 75.0% of the patients had read the entire pain brochure, 55.7% had listened to the audio cassette, and 85.6% of pain scores were completed in the pain diary. Results showed a significant increase in pain knowledge in patients who received the Pain Education Program and a significant decrease in pain intensity. However, pain relief was mainly found in the intervention group patients without district nursing. It can be concluded that the tailored Pain Education Program is effective for cancer patients in chronic pain. The use of the Pain Education Program by nurses should be seriously considered on oncology units.", "The efficacy of energy conservation and activity management (ECAM) for fatigue reduction and maintenance of functional performance has never been evaluated in adults with cancer who are undergoing treatment.\n A randomized clinical trial compared an ECAM intervention with a control intervention focused on nutrition. Individuals initiating chemotherapy, radiotherapy, or concurrent therapy for cancer were randomized to receive either the semistructured ECAM intervention (n = 200) or the control intervention (n = 196). Participants in each group participated in 3 telephone sessions with an oncology nurse during the first 5 weeks of treatment. Data on fatigue and limitation of functioning were obtained before cancer treatment and at two follow-up points that coincided with times of high fatigue for each type of treatment. The outcomes of interest included perception of fatigue and functional performance.\n A repeated-measures analysis of covariance using the type of cancer treatment as a covariate revealed a significant study group-by-time interaction indicating that the ECAM group experienced a greater decrease in fatigue over time compared with the control group (F(2,544) = 4.5; P = 0.01). The intervention was not associated with changes in overall functional performance.\n Individuals who received the ECAM intervention derived a modest but significant benefit from it. To achieve a more robust clinical benefit from the intervention, it may be necessary to manage other key symptoms in addition to fatigue. Research is needed to examine symptom clusters or combinations associated with negative outcomes as well as combination strategies for symptom management.\n Copyright 2004 American Cancer Society.", "The authors determined the effects of ongoing weekly individual psychotherapy on the symptoms of patients undergoing a 6-week course of radiotherapy for cancer. Forty-eight patients were given weekly psychotherapy sessions for 10 weeks; another 52 patients served as control subjects. A statistically significant reduction was found in both emotional and \"physical\" manifestations of distress in the patients receiving psychotherapy compared with the control group. This was true regardless of gender, ward or private patient status, or knowledge of diagnosis. Patient gender and knowledge of diagnosis did affect the pattern and magnitude of the response to psychotherapy.", "This study evaluated a supportive intervention for fatigue in patients undergoing chemotherapy. One hundred three chemotherapy-naïve patients were recruited, stratified by treatment regimen, and randomly allocated to intervention or usual care. The intervention was conducted over three months. Recipients were provided with an investigator-designed information pack and Fatigue Diary that they completed during the week following each treatment. Additionally, support nurses visited them monthly at home. They assessed fatigue, provided psychological support, and coached participants in self-care. The intervention group reported significantly less fatigue (P < 0.05), lower associated distress (P < 0.05), and less impact of fatigue on valued pastimes (P < 0.05) than the control group. Further, they reported significantly less anxiety (P < 0.05) and depression (P < 0.05) and displayed more adaptive coping (P < 0.05). The intervention enabled patients to adapt to living with fatigue and contributed to their psychological/emotional well-being and ability to cope with their illness and treatment.", "This study reports results from a randomised controlled trial of nurse-led care and was designed to determine whether nurse-led follow up improved patients morbidity and satisfaction with care in men treated with radical radiotherapy for prostate and bladder cancer. The aim was to compare outcomes in terms of toxicity, symptoms experienced, quality of life, satisfaction with care and health care costs, between those receiving nurse-led care and a group receiving standard care. The study population was of men prescribed radical radiotherapy (greater than 60 Gy). Participants completed self-assessment questionnaires for symptoms and quality of life within the first week of radiotherapy treatment, at week 3, 6 and 12 weeks from start of radiotherapy. Satisfaction with clinical care was also assessed at 12 weeks post-treatment. Observer-rated RTOG toxicity scores were recorded pre-treatment, weeks 1, 3, 6 and 12 weeks from start of radiotherapy. The results presented in this paper are on 115 of 132 (87%) of eligible men who agreed to enter the randomised trial. 6 men (4%) refused and 11 (8%) were missed for inclusion in the study. Data were analysed as a comparison at cross-sectional time points and as a general linear model using multiple regression. There was no significant difference in maximum symptom scores over the time of the trial between nurse-led follow-up care and conventional medical care. Differences were seen in scores in the initial self assessment of symptoms (week 1) that may have been as a result of early nursing intervention. Those men who had received nurse-led care were significantly more satisfied (P < 0.002) at 12 weeks and valued the continuity of the service provided. There were also significant (P < 0.001) cost benefits, with a 31% reduction in costs with nurse-led, compared to medically led care. Evidence from this study suggests that a specialist nurse is able to provide safe follow up for men undergoing radiotherapy. The intervention focused on coping with symptoms, and provided continuity of care and telephone support. Further work is required to improve the management of patients during and after radiotherapy.", "The aim of this study was to evaluate the effect of psychosocial rehabilitation on newly diagnosed prostate cancer patients. The \"Between Men\" programme consisted of seven weekly sessions of physical training (Phys) alone, information (Info) alone or physical training plus information (PhysInfo). After diagnoses, patients (n = 211) were consecutively included, stratified and randomised to one of four groups: Phys, Info, PhysInfo or standard care control (C). A nurse specialised in urology, an urologist and a physiotherapist performed the interventions. Patients were followed up during one year with mailed standardised questionnaires. It could not be assumed that the \"Between Men\" programme had any effect on patients' anxiety and depression (HADS). Health-related quality of life (HRQOL) was associated with stage of disease but not with psychosocial intervention. Thus, Physical Function (PF), Role Function (RF) and Fatigue (FA) were inferior among patients with, than without, metastases of prostate cancer both at baseline and at the 12-month follow-up. This randomized study did not demonstrate any significant effect of psychosocial rehabilitation among prostate cancer patients. Considering the low rate (1/2), of included/eligible patients a less complicated design (intervention versus control) would have been preferred in order to increase power.", "It has been shown that nonpharmacologic interventions are effective management techniques for cancer-related fatigue (CRF) in cancer survivors. However, few studies have investigated their effectiveness in patients who are receiving chemotherapy. In this study, the authors tested the effectiveness of a brief behaviorally oriented intervention in reducing CRF and improving physical function and associated distress in individuals who were receiving chemotherapy.\n For this randomized controlled trial, 60 patients with cancer were recruited and received either usual care or the intervention. The intervention was delivered on an individual basis on 3 occasions over a period from 9 weeks to 12 weeks, and the objective of the intervention was to alter fatigue-related thoughts and behavior. Primary outcomes were assessed as follows: CRF using the Visual Analogue Scale-Global Fatigue; physical functioning using the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 Questionnaire, and CRF-associated distress using the Fatigue Outcome Measure. Assessments were made on 4 occasions: at baseline (T0), at the end of chemotherapy (T1), 1 month after chemotherapy (T2), and 9 months after recruitment (T3). Normally distributed data were analyzed using t tests and random-slope/random-intercept mixed models.\n The intervention demonstrated a trend toward improved CRF, although this effect was reduced once confounders had been controlled statistically. There was a significant improvement in physical functioning (coefficient, 10.0; 95% confidence interval, 2.5-17.5; P = .009), and this effect remained once the confounding effects of mood disturbance and comorbid disorders were controlled statistically. No decrease in fatigue-related distress was detected.\n The behaviorally oriented intervention brought about significant improvements in physical functioning, indicated a trend toward improved CRF, but detected no effect for fatigue-related distress.\n (c) 2007 American Cancer Society.", "To test the effects of a computer-based nursing intervention designed to provide patients and family caregivers with concrete, objective information on symptom management; provide education about disease and treatment; coordinate medical resources; and provide emotional support and counseling.\n Two-site, randomized clinical trial.\n A large, urban, midwestern, tertiary-cancer center and a community-based cancer center in a medium-sized midwestern city.\n 109 patients newly diagnosed with breast, colon, or lung cancer who were receiving chemotherapy; 54 received standard care, and 55 participated in the intervention group.\n Outcome data were collected via structured telephone interviews at three time points: baseline, midway through the intervention, and one month postintervention. The intervention consisting of nine visits, five in person and four by telephone, was conducted over 18 weeks by advanced practice oncology nurses.\n Psychosocial functioning, anxiety, and depression.\n Patients who received the intervention had significantly less depression between baseline and the midway point, as well as less anxiety and greater improvement in the role-emotional and mental health subscales of the Medical Outcomes Study 36 Short Form.\n Cancer-care nursing interventions can decrease psychosocial morbidity and improve quality of life for newly diagnosed patients with cancer undergoing treatment. Additional research is needed to understand who benefited most from the intervention.\n This nurse-directed intervention resulted in improved mental health for patients; however, physical subscales were not changed. Further work is needed to determine why depression and mental health were affected yet physical health and symptoms did not differ between groups. Results support the important role of nurses in addressing mental health issues in patients and families experiencing cancer.", "To evaluate the efficacy of a psychoeducational intervention in improving cancer-related fatigue.\n This randomized controlled trial involved 109 women commencing adjuvant chemotherapy for stage I or II breast cancer in five chemotherapy treatment centers. Intervention group patients received an individualized fatigue education and support program delivered in the clinic and by phone over three 10- to 20-minute sessions 1 week apart. Instruments included a numeric rating scale assessing confidence with managing fatigue; 11-point numeric rating scales measuring fatigue at worst, average, and best; the Functional Assessment of Cancer Therapy-Fatigue and Piper Fatigue Scales; the Cancer Self-Efficacy Scale; the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; and the Hospital Anxiety and Depression Scale. For each outcome, separate analyses of covariance of change scores between baseline (T1) and the three follow-up time points (T2, T3, and T4) were conducted, controlling for the variable's corresponding baseline value.\n Compared with the intervention group, mean difference scores between the baseline (T1) and immediate after the test (T2) assessments increased significantly more for the control group for worst and average fatigue, Functional Assessment of Cancer Therapy-Fatigue, and Piper fatigue severity and interference measures. These differences were not observed between baseline and T3 and T4 assessments. No significant differences were identified for any pre- or post-test change scores for confidence with managing fatigue, cancer self-efficacy, anxiety, depression, or quality of life.\n Preparatory education and support has the potential to assist women to cope with cancer-related fatigue in the short term. However, further research is needed to identify ways to improve the potency and sustainability of psychoeducational interventions for managing cancer-related fatigue.", "Depression is particularly prevalent in patients with advanced cancer. Cognitive therapy (CT) is an empirically supported treatment for depression in the general population. However, efficacy remains to be demonstrated in patients with advanced cancer. A prior controlled trial of CT in a group format showed improvements in depression, mood disturbance, and self-esteem; however, these effects were not maintained over time. Studies examining the efficacy of individual format CT interventions that may ensure more long-term maintenance of benefits are necessary. This study assessed the efficacy of CT for depression administered individually in women with metastatic breast cancer and its effect on immune function.\n Forty-five women were randomly assigned to either individual CT or to a waiting-list control (WLC) condition. CT was composed of eight weekly sessions of CT and three booster sessions administered at 3-week intervals following the end of treatment.\n Patients treated with CT had significantly lower scores on the Hamilton Depression Rating Scale at posttreatment compared to untreated patients. Pooled data from both groups indicated significant reductions of depressive symptoms from pre- to posttreatment, as well as reduction of associated symptoms including anxiety, fatigue, and insomnia symptoms. These effects were well sustained at the 3- and 6-month follow-up evaluations. CT for depression did not appear to have a significant impact on immune functioning.\n Findings of this study support the efficacy of CT for depression in this population and suggest that the administration of individual and booster sessions after treatment termination may be instrumental in sustaining the treatment effects over time.", "Supportive-expressive group therapy has been reported to prolong survival among women with metastatic breast cancer. However, in recent studies, various psychosocial interventions have not prolonged survival.\n In a multicenter trial, we randomly assigned 235 women with metastatic breast cancer who were expected to survive at least three months in a 2:1 ratio to an intervention group that participated in weekly supportive-expressive group therapy (158 women) or to a control group that received no such intervention (77 women). All the women received educational materials and any medical or psychosocial care that was deemed necessary. The primary outcome was survival; psychosocial function was assessed by self-reported questionnaires.\n Women assigned to supportive-expressive therapy had greater improvement in psychological symptoms and reported less pain (P=0.04) than women in the control group. A significant interaction of treatment-group assignment with base-line psychological score was found (P</=0.003 for the comparison of mood variables; P=0.04 for the comparison of pain); women who were more distressed benefited, whereas those who were less distressed did not. The psychological intervention did not prolong survival (median survival, 17.9 months in the intervention group and 17.6 months in the control group; hazard ratio for death according to the univariate analysis, 1.06 [95 percent confidence interval, 0.78 to 1.45]; hazard ratio according to the multivariate analysis, 1.23 [95 percent confidence interval, 0.88 to 1.72]).\n Supportive-expressive group therapy does not prolong survival in women with metastatic breast cancer. It improves mood and the perception of pain, particularly in women who are initially more distressed.", "Stress, anxiety, and depression in patients who are undergoing treatment of cancer significantly compromise the quality of their lives. The impact of stress reduction by relaxation training and imagery was studied in 82 out-patients who were undergoing curative (73 patients) or palliative (9 patients) radiotherapy. Fifty-two females and 30 males were assigned randomly to a relaxation training condition (34 patients) as an adjunct to radiation or a control condition (29 patients), which entailed education and counseling along with the RT. Using pre- and posttests of the Profile of Mood States, significant (p less than .01) reductions were noted in the treatment group in tension, depression, anger, and fatigue. The results suggest that relaxation training substantially improves several psychological parameters associated with quality of life in ambulatory patients who are undergoing radiation therapy.", "Through a randomized clinical trial, to compare patients undergoing an initial course of chemotherapy who report pain and fatigue at baseline and who are receiving conventional care alone with those receiving conventional care plus a nursing intervention on outcomes reported at 20 weeks.\n Chemotherapy clinics of two comprehensive and two community cancer centers.\n Interviews were conducted at baseline and 10 and 20 weeks. An 18-week, 10-contact nursing intervention utilizing problem-solving approaches to symptom management and improving physical functioning and emotional health was implemented.\n The sample consisted of 53 patients in the experimental arm and 60 in the control arm who reported pain and fatigue at baseline.\n Pain and fatigue, numbers of other symptoms, and physical role impact and social-functioning subscales from the Medical Outcomes Study 36 Short Form.\n Patients who received the intervention reported a significant reduction in the number of symptoms experienced and improved physical and social functioning. Fewer patients in the experimental arm reported both pain and fatigue at 20 weeks.\n Behavioral interventions targeted to patients with pain and fatigue can reduce symptom burden, improve the quality of the daily life of patients, and demonstrate the \"value-added\" role of nursing care for patients undergoing chemotherapy.\n These data support the \"value-added\" role of nursing interventions for symptom management and improved quality of life during the course of cancer treatment.", "Quality of life (QOL) of cancer patients is often diminished due to the side effects of treatment and symptoms of the disease itself. Medical Qigong (coordination of gentle exercise and relaxation through meditation and breathing exercise based on Chinese medicine theory of energy channels) may be an effective therapy for improving QOL, symptoms and side effects, and longevity of cancer patients. In this pilot study, the feasibility, acceptability, and impact of Medical Qigong (MQ) were evaluated on outcomes in cancer patients. Thirty patients diagnosed with heterogeneous cancers, were randomly assigned to two groups: a control group that received usual medical care and an intervention group who participated in a MQ program for 8 weeks in addition to receiving usual medical care. Randomization was stratified by completion of cancer treatment (n = 14) or under chemotherapy (n = 16). Patients completed measures before and after the program. Quality of life and symptoms were measured by the EORTC QLQ-C 30 and progress of disease by the inflammation biomarker (CRP: c-reactive protein) via a blood test was assessed. The MQ intervention group reported clinically significant improved global QOL scores pre- and post-intervention. The MQ intervention also reduced the symptoms of side effects of cancer treatment and inflammation biomarker (CRP) compare to the control group. Due to the small sample size, however, the results were not statistically significant between treatment and the control groups. Data from the pilot study suggest that MQ with usual medical treatment can enhance the QOL of cancer patients and reduce inflammation. This study needs a further investigation with a larger sample size.", "The effects of weekly supportive group meetings for women with metastatic carcinoma of the breast were systematically evaluated in a one-year, randomized, prospective outcome study. The groups focused on the problems of terminal illness, including improving relationships with family, friends, and physicians and living as fully as possible in the face of death. We hypothesized that this invention would lead to improved mood, coping strategies, and self-esteem among those in the treatment group. Eighty-six patients were tested at four-month intervals. The treatment group had significantly lower mood-disturbance scores on the Profile of Mood States scale, had fewer maladaptive coping responses, and were less phobic than the control group. This study provides objective evidence that a supportive group intervention for patients with metastatic cancer results in psychological benefit. Mechanisms underlying the effectiveness of this group intervention are explored.", "People with cancer have identified fatigue as a major obstacle to normal functioning and a good quality of life. It is a nearly universal symptom for patients undergoing primary antineoplasic therapy or treatment with biologic response modifiers (BRM) and is extremely common in patients with persistent or advanced disease. The aim of the study was to determine whether nursing education decreased the perception of fatigue in patients with colon or gastric cancer. We compared the fatigue level between two groups of patients who received the same treatment and had the same type of cancer (experimental group and control group). We provided an individualised and structured nursing intervention with education to the experimental group. We followed up the fatigue level in both groups with three different measures on the Functional Assessment of Cancer Therapy Fatigue (FACT-F) Scale. After the nursing intervention there was a decrease in the level of fatigue in the experimental group, whereas the group of patients that did not receive this intervention showed an increase in fatigue level along the treatment. The nursing intervention with the individualised education and counselling has provided patients with cancer with an effective tool to manage fatigue.", "Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control.\n Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population.\n Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition.\n Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.", "One-hundred and twenty-four patients with metastatic breast cancer were randomised to either a group Cognitive Behaviour Therapy (CBT) intervention, or to a no-therapy control group condition. Both groups received standard oncological care; however, therapy recipients also attended eight weekly sessions of group CBT, followed by a family night, and three further monthly sessions. Patients completed the 'Profile of Mood States' (POMS) and the Coopersmith Self-esteem Inventory (CSI) before and after therapy, and at 3 and 6 month follow-up periods. Outcome data in the period following therapy showed reduced depression and total mood disturbance, as well as improved self-esteem amongst therapy participants, relative to a no-therapy control group. These improvements were no longer evident at the 3 or 6 month follow-up assessments. We also report on the difficulties associated with conducting a group intervention with this patient cohort.", "To test the value of telephone-administered cognitive-behavioral therapy in a study of patients with breast cancer.\n Women were assigned randomly to a therapy group or an assessment-only control group.\n A tertiary cancer treatment center serving rural areas of North Dakota and Minnesota.\n Women were recruited within three to four months of stage I (n = 27) or stage II (n = 26) breast cancer diagnosis. Age ranged from 30-82 (mean = 51.5 years). Most participants (n = 35) underwent a modified radical mastectomy; 17 underwent a lumpectomy.\n Therapy involved 10 30-minute (or less) telephone sessions. Data that were collected from mailed questionnaires included psychological distress (Profile of Mood States), perceived stress, coping (Coping Response Indices-Revised), quality of life (Medical Outcome Scale), and satisfaction with therapy. Measures were completed at baseline and at 4- and 10-month follow-up intervals.\n Telephone therapy, stress, coping, and quality of life.\n With time, women in the therapy and control groups reported reduced stress and improved quality of life. However, significant reductions in some kinds of distress (anxiety, anger, depression, and confusion) were not observed. Most therapy participants liked the telephone treatment sessions but showed only modest improvement (less anxiety and confusion) compared with women in the control group.\n Most patients reported being comfortable with the telephone therapy and said that they felt better as a result of it. However, the outcome data showed that telephone therapy--as carried out in this study--produced only modest benefits. Researchers need to consider who is best for delivering such therapy.\n Providing telephone therapy to patients with breast cancer has potential benefits, and nurses may be the appropriate professionals to administer the therapy.", "The primary purpose of this study was to determine if a psychoeducational nursing intervention including (a) health education, (b) stress management, and (c) the teaching of coping skills could enhance the coping behavior and affective state of newly diagnosed Stage I/II malignant melanoma patients. The secondary purpose was to determine if this intervention could be implemented by a nurse and integrated into the overall patient care program. Sixty-one patients were randomized to a control condition or an experimental condition that received and educational manual plus 3 h of individual nurse teaching. Despite randomization, experimental patients had significantly higher baseline distress. By 3 months there was a complete reversal of the baseline trend in Profile of Mood States (POMS) total mood disturbance (TMD), suggesting that the experimental subjects were experiencing less distress over time. Between-group analysis of change scores found significant decreases in experimental subjects for POMS TMD, fatigue, and Brief Symptom Index (BSI) somatization. Within-group analysis found significant experimental decreases for BSI somatization, anxiety, grand total, General Severity Index, and Positive Symptom Distress Index as well as for POMS anxiety, fatigue, confusion, vigor, and TMD. No significant changes were found for controls. Experimental patients were using significantly fewer ineffective passive resignation coping strategies than controls at 3 months.", "The authors report the short-term effects of a clinical trial testing 2 telephone therapies for breast cancer patients. Women (N = 222) with breast cancer were recruited and randomly assigned to cancer education, emotional expression, or standard care. Oncology nurses conducted 6 individual 30-min-therapy phone sessions. Women in the cancer education condition reported greater perceived control than women in the standard care condition. No treatment effects were obtained for mood or quality of life. These are the 1st data from a large-scale study testing telephone therapy, and they suggest that such therapies may be ineffective. Explanations for the results include therapy type and delivery, participant characteristics, short- versus long-term results, therapy conent, and whether therapy is necessary for breast cancer patients.", "Patients with breast cancer who undergo autologous bone marrow/peripheral blood stem cell transplantation (ABMT) cope not only with a life-threatening medical treatment, but also with multiple, interrelated symptoms including pain, fatigue, psychological distress, and nausea. The purpose of this study was to determine, in a randomized controlled clinical trial, whether a comprehensive coping strategy program (CCSP) was effective in significantly reducing pain, fatigue, psychological distress, and nausea in patients with breast cancer who underwent ABMT. The CCSP was composed of preparatory information, cognitive restructuring, and relaxation with guided imagery. Randomization placed 52 patients in the CCSP treatment group and 58 patients in the control group. The CCSP was found to be effective in significantly reducing nausea as well as nausea combined with fatigue 7 days after the ABMT when the side effects of treatment were most severe. These results are important given the high incidence of nausea and fatigue in the ABMT population. The CCSP-treated group experienced mild anxiety as compared with the control group who reported moderate anxiety. The greatest effectiveness of CCSP may correspond to the time of the greatest morbidity for patients with breast cancer who have undergone ABM.", "Forty-two patients with metastatic renal cell carcinoma who were participating in a Phase II clinical trial were randomly assigned to an expressive writing (EW) or neutral writing (NW) group. Patients in the EW group wrote about their cancer, and patients in the NW group wrote about health behaviors. No statistically significant group differences were found in symptoms of distress, perceived stress, or mood disturbance, except for the Vigor subscale of the Profile of Mood States. However, patients in the EW group reported significantly less sleep disturbance, better sleep quality and sleep duration, and less daytime dysfunction compared with patients in the NW group. The results suggest that EW may have sleep-related health benefits in terminally ill cancer patients." ]

[ "17949458", "15666380", "17697262", "16555338" ]

[ "The ischemic preconditioning paradox in deceased donor liver transplantation-evidence from a prospective randomized single blind clinical trial.", "Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy.", "Ischemic pre-conditioning in deceased donor liver transplantation: a prospective randomized clinical trial.", "Effect of ischemic preconditioning in whole liver transplantation from deceased donors. A pilot study." ]

[ "While animal studies show that ischemic preconditioning (IPC) is beneficial in liver transplantation (LT), evidence from few smaller clinical trials is conflicting. From October 2003 to July 2006, 101 deceased donors (DD) were randomized to 10 min IPC (n = 50) or No IPC (n = 51). Primary objective was efficacy of IPC to decrease reperfusion (RP) injury. Both groups had similar donor risk index (DRI) (1.54 vs. 1.57). Aminotransferases on days 1 and 2 were significantly greater (p < 0.05) in IPC recipients. In multivariate analyses, IPC had an independent effect only on day 2 aspartate transferase. Prothrombin time, bilirubin and histological injury were similar in both groups. IPC had no significant effect on plasma TNF-alpha, IL-6 and IL-10 in the donor and TNF-alpha and IL-6 in the recipient. In contrast, IPC recipients had a significant rise in systemic IL-10 levels after RP (p < 0.05) and had fewer moderate/severe rejections within 30 days (p = 0.09). Hospital stay was similar in both groups. One-year patient and graft survival in IPC versus No IPC were 88% versus 78% (p = 0.1) and 86 versus 76% (p = 0.25), respectively. IPC increases RP injury after DDLT, an 'IPC paradox'. Other potential benefits of IPC are limited. IPC may be more effective in combination with other preconditioning regimens.", "Ischemic preconditioning (IPC) has the potential to decrease graft injury and morbidity after liver transplantation. We prospectively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers randomized 1:1 to standard (STD) recovery (N = 28) or IPC (N = 34). Safety was assessed by measurement of heart rate, blood pressure, and visual inspection of abdominal organs during recovery, and efficacy by recipient aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT], both measured in U/L), total bilirubin, and international normalized ratio of prothrombin time (INR) after transplantation. IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion. Recipient median AST, median ALT, and mean INR, in STD vs. IPC were as follows: day 1 AST 696 vs. 841 U/L; day 3 AST 183 vs. 183 U/L; day 1 ALT 444 vs. 764 U/L; day 3 ALT 421 vs. 463 U/L; day 1 INR 1.7 +/- .4 vs. 2.0 +/- .8; and day 3 INR 1.3 +/- .2 vs. 1.4 +/- .3; all P > .05. No instances of nonfunction occurred. The 6-month graft and patient survival STD vs. IPC were 82 vs. 91% and median hospital stay was 10 vs. 8 days; both P > .05. In conclusion, deceased donor livers tolerated 5 minutes of hilar clamping well, but IPC did not decrease graft injury. Further trials with longer periods of preconditioning such as 10 minutes are needed.", "To assess the immediate and long-term effects of ischemic preconditioning (IPC) in deceased donor. liver transplantation (LT), we designed a prospective, randomized controlled trial involving 60 donors: control group (CTL, n = 30) or study group (IPC, n = 30). IPC was induced by 10-min hiliar clamping immediately before recovery of organs. Clinical data and blood and liver samples were obtained in the donor and in the recipient for measurements. IPC significantly improved biochemical markers of liver cell function such as uric acid, hyaluronic acid and Hypoxia-Induced Factor-1 alpha (HIF-1 alpha) levels. Moreover, the degree of apoptosis was significantly lower in the IPC group. On clinical basis, IPC significantly improved the serum aspartate aminotransferase (AST) levels and reduced the need for reoperation in the postoperative period. Moreover, the incidence of primary nonfunction (PNF) was lower in the IPC group, but did not achieve statistical significance. We conclude that 10-min IPC protects against I/R injury in deceased donor LT.", "The effect of ischemic preconditioning (IPC) in orthotopic liver transplantation (OLT) has not yet been clarified. We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors randomly assigned to receive (IPC+ group, n = 23) or not (IPC- group, n = 24) IPC (10-min ischemia + 15-min reperfusion). In 10 cases in the IPC+ group and in 12 in the IPC- group, the expression of inducible nitric oxide synthase (iNOS), neutrophil infiltration, and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies. Median aspartate aminotransferase (AST) levels were lower in the IPC+ group vs. the IPC- group on postoperative days 1 and 2 (398 vs. 1,234 U/L, P = 0.002; and 283 vs. 685 U/L, P = 0.009). Alanine aminotransferases were lower in the IPC+ vs. the IPC- group on postoperative days 1, 2, and 3 (333 vs. 934 U/L, P = 0.016; 492 vs. 1,040 U/L, P = 0.008; and 386 vs. 735 U/L, P = 0.022). Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks, incidence of graft nonfunction and graft and patient survival rates were similar between groups. Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups. iNOS was higher postreperfusion vs. prereperfusion in the IPC- group (P = 0.008). Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups (IPC+, P = 0.007; IPC-, P = 0.003). Prereperfusion and postreperfusion apoptosis was minimal in both groups. In conclusion, IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis, but it showed no clinical benefits.\n Copyright 2006 AASLD" ]

[ "11243292", "8228713", "3748494", "1303479", "3079625", "9894177", "7447362", "9251949", "2798994", "12790845", "3772891", "1568631", "2315771", "2183617", "16212202", "3907340", "6293721" ]

[ "Antibiotic prophylaxis at Cesarean delivery.", "An efficacy study of ampicillin versus cefazolin prophylaxis in patients undergoing cesarean section.", "Randomized comparison of five irrigation solutions at cesarean section.", "The role of prophylactic antibiotics in caesarean section--a randomised trial.", "A double-blind, controlled comparison of piperacillin and cefoxitin in the prevention of postoperative infection in patients undergoing cesarean section.", "Incidence of postpartum endomyometritis following single-dose antibiotic prophylaxis with either ampicillin/sulbactam, cefazolin, or cefotetan in high-risk cesarean section patients.", "Prophylactic antibiotics in Caesarean section: effect of a short preoperative course of benzyl penicillin or clindamycin plus gentamicin on postoperative infectious morbidity.", "Ampicillin/sulbactam versus cefotetan for the prevention of infection following cesarean delivery in high-risk patients: a randomized double-blind trial.", "[Antibiotic prophylaxis in non-elective cesarean section with single-dose imipenem versus multiple-dose cefotaxime].", "Choice of antibiotics for infection prophylaxis in emergency cesarean sections in low-income countries: a cost-benefit study in Mozambique.", "Single-dose antibiotic prophylaxis in high-risk patients undergoing cesarean section. A comparative trial.", "[The effectiveness of preventive use of antibiotics in Cesarean section with a single dose: comparison of cefotaxime with amoxicillin plus clavulanic acid].", "Antibiotic prophylactic uterine lavage in cesarean section: a double-blind comparison of saline, ticarcillin, and cefoxitin irrigation in indigent patients.", "Antibiotic prophylaxis: is there a difference?", "Ceftriaxone versus ampicillin/cloxacillin as antibiotic prophylaxis in elective caesarean section.", "Ticarcillin plus clavulanic acid versus cefoxitin in the prophylaxis of infection after cesarean section.", "Cefotaxime, cefazolin, or ampicillin prophylaxis of febrile morbidity in emergency cesarean sections." ]

[ "Our aim was to compare the efficacy of ampicillin, cefotetan, and ampicillin/sulbactam in the prevention of post-Cesarean endomyometritis.\n Consenting patients undergoing Cesarean delivery at the University of Louisville Hospital were enrolled in a prospective, double-blinded randomization to receive either ampicillin/sulbactam (Group 1), cefotetan (Group 2), or ampicillin (Group 3) single dose antibiotic prophylaxis following umbilical cord clamping. The primary outcome variable was the frequency of endomyometritis in the respective groups.\n Among 301 randomized patients, outcome data was available for 298 patients. Fourteen patients (4.7%), all of whom underwent non-elective Cesarean delivery, developed endomyometritis. The frequency of endomyometritis was not different among groups: Group 1, 4/101 (4%); Group 2, 4/96 (4.2%); and Group 3, 6/101 (5.9%). Wound infections were infrequently observed 4/298 (1.3%) without significant differences among groups. Stepwise discriminative analysis identified only last cervical dilatation as a significant predictor of endomyometritis (P = 0.006).\n Post-Cesarean endomyometritis occurs infrequently following single dose antibiotic prophylaxis after umbilical cord clamping. An advantage of broader spectrum antibiotics over ampicillin was not demonstrated.", "nan", "A randomized double-blind study was undertaken to determine which irrigation solution might be best at cesarean section. A saline placebo was compared with ampicillin sodium and one each of three generations of cephalosporins: cephapirin sodium, cefamandole nafate, and moxalactam disodium. A total of 360 cesarean sections were studied, and comparisons made between antibiotic and control groups relative to demographics, possible risk factors, and multiple measures of postoperative morbidity. The total group was further divided into high- and low-risk labor and repeat cesarean groups. Post-cesarean endometritis was diagnosed in the following frequencies for the group as a whole: placebo (24.6%), ampicillin sodium (8.5%), cephapirin sodium (11.4%), cefamandole nafate (4.6%), and moxalactam disodium (16.4%). Cefamandole nafate consistently demonstrated significant decreases in endometritis and other morbidity measures versus placebo both in laboring patients and the group as a whole.", "A prospective randomised controlled study was conducted over a 6 month period on the value of administering prophylactic antibiotics in patients undergoing emergency caesarean section at the Ipoh General Hospital. A total of 222 patients were randomised to receive 24 hours of ampicillin (500 mg per dose), cefoperazone (1 gm per dose) or no antibiotics. In all parameters of patient morbidity, the group receiving cefoperazone showed significantly better results as compared to the group not receiving antibiotics. The ampicillin group also had favourable results but generally not achieving statistical significance. Prophylactic antibiotics appear to be beneficial and consideration should be given to make it a routine in all emergency caesarean sections.", "Data are presented from a randomized, double-blind multicenter trial (six study sites, involving 346 patients) in which piperacillin was compared with cefoxitin as a prophylactic agent for patients undergoing cesarean section. One hundred and sixty-nine patients received piperacillin and 177 received cefoxitin; in each instance, the total dosage was 6 grams. Strict criteria were used to evaluate safety and efficacy. The courses of all of the patients were evaluable for safety and 183 courses were evaluable for efficacy (136 efficacy-evaluable courses were from patients treated with piperacillin and 147, from those treated with cefoxitin). Postoperative infection was prevented in 89 per cent of the patients treated with piperacillin and in 93 per cent of the those treated with cefoxitin. The difference was not statistically significant. The data from each of the individual study sites, as well as the pooled data, indicated that the short term perioperative administration of piperacillin in patients undergoing a cesarean section was as safe and effective as cefoxitin with regard to prophylactic response, duration of hospitalization and the usage of other systemic antibiotics.", "To assess the efficacy of single-dose antibiotic prophylaxis against postpartum endomyometritis in high-risk cesarean section patients.\n Patients were administered one of three single-dose antibiotic regimens following umbilical cord clamping after cesarean section delivery.\n Prospective randomized trial at a university-based hospital.\n The study evaluated 293 consenting women undergoing cesarean section who had either experienced labor for a duration of > or = 6 hr or rupture of amniotic membranes.\n Development of postpartum endomyometritis.\n The incidence of postpartum endomyometritis was 7/95 (7.4%) following the ampicillin/sulbactam regimen, 14/98 (14.3%) after the cefazolin regimen, and 11/99 (11.1%) after the cefotetan regimen. There was no significant difference in postpartum infection among the three study arms. In addition, the incidence of endomyometritis in the three single-dose study arms was not higher than previously noted in studies where three doses of antibiotic were administered.\n Single-dose antibiotic prophylaxis should replace the standard triple-dose therapy for uninfected women undergoing cesarean section who are at risk for postoperative endomyometritis. Ampicillin/sulbactam, cefazolin, and cefotetan are all reasonable antibiotic choices for single-dose therapy.", "The efficacy of a narrow-spectrum (benzyl penicillin) versus broad-spectrum (clindamycin + gentamicin) preoperative antimicrobial prophylaxis was studied in a series of 147 consecutive patients undergoing Caesarean section at the State Maternity Hospital, Helsinki, Finland. Both regimens proved effective in reducing postoperative endometritis: from 33% (19/57 cases) to 6.5% (3/46 cases) in the penicillin treated group, and to 9.5% (4/42 cases) in the clindamycin + gentamicin treated group. The reduction in the incidence of endometritis was not reflected in the duration of hospital stay, which was 7.7 days in the untreated group, 7.8 days in the penicillin treated group, and 7.6 days in the clindamycin + gentamicin treated group. No significant differences between the groups were detected in the incidence of wound infections.", "The objective of this study was to compare the efficacy and safety of a single intravenous dose of 1 g ampicillin plus 0.5 g sulbactam to a single intravenous dose of 1 g cefotetan in the prevention of postoperative infection following cesarean delivery in high-risk patients. In this single-center comparative study, women who were to undergo cesarean delivery and who were at high risk of developing postoperative infection were randomized into two treatment groups. At the time the umbilical cord was clamped, one group was treated intravenously with 1 g ampicillin plus 0.5 g sulbactam, and the other was treated intravenously with 1 g cefotetan. The two groups were evaluated for evidence of postoperative infections and adverse experiences. A total of 170 women who were at high risk of developing postoperative infection following cesarean delivery (87 in the ampicillin/sulbactam group and 83 in the cefotetan group) were analyzed. Successful prophylaxis, absence of any infection including absence of febrile morbidity with no other symptoms, was reported in 69 of 87 (79%) patients receiving ampicillin/sulbactam and in 60 of 83 (72%) patients receiving cefotetan. One patient in each group had an infection at the incision site. There were no statistically significant differences in the rates of endometritis or urinary tract infections. The mean duration of hospitalization was 5.5 days for patients receiving ampicillin/sulbactam and 5.7 days for patients receiving cefotetan. A single intravenous dose of the combination of ampicillin/sulbactam was as safe and effective as a single intravenous dose of cefotetan when administered for the prevention of infections following cesarean delivery in patients at high risk of developing postoperative morbidity. Both antibiotics were safe and well tolerated with no unusual or unexpected events.", "Antibiotic prophylaxis reduces the incidence of febrile morbidity in women undergoing non-elective cesarean section. A randomized comparison of prophylactic single dose Imipenem, a carbapenem antibiotic with the broadest antimicrobial spectrum of activity of any antibiotic, with multiple doses Cefotaxime, a third generation cephalosporin, was undertaken in 48 women who underwent non-elective cesarean section (22 receiving Imipenem, 26 Cefotaxime). The incidence of febrile morbidity in the Imipenem group was 4.54% versus 7.69 in patients receiving multiple doses of Cefotaxime. There were non serious complications in the treated groups.", "There is a need to assess the cost-benefit of different models of antibiotic administration for the prevention of post cesarean infection, particularly in resource-scarce settings.\n Randomized, nonblinded comparative study of a single combined preoperative dose of gentamicin and metronidazole vs. a post cesarean scheme for infection prophylaxis.\n Pregnant women (n = 288) with indication for emergency cesarean section were randomly allotted to two groups. Group 1 (n = 143) received the single, combined dose of prophylactic antibiotics and group 2 (n = 145) received, over 7 days, the postoperative standard scheme of antibiotics followed in the department. Both groups were followed up during 7 days for detection of signs of wound infection, endometritis, peritonitis and urinary tract infection.\n Prevalence of postoperative infection, mean hospital stay and costs of antibiotics used.\n Women completing the study (n = 241) were distributed into group 1 (n = 116) and group 2 (n = 125). No significant difference was found neither in the prevalence of postoperative infection nor in the mean hospital stay. No death occurred. The cost of the single dose of prophylactic antibiotics was less than one-tenth of the cost of the standard postoperative scheme.\n In our setting, the administration of a single dose of 160 mg of gentamicin in combination with 500 mg of metronidazole before emergency cesarean section for prevention of infection is clinically equivalent to existing conventional week-long postoperative therapy, but at approximately one-tenth of the cost.", "A prospective, double-blind study was performed to evaluate the comparative efficacy of single- and multiple-dose antimicrobial prophylaxis for preventing infection in high-risk patients undergoing cesarean section. One hundred fifty-eight patients were randomly assigned to receive either a single perioperative dose of mezlocillin, three doses of mezlocillin or three doses of cefoxitin. The incidence of endometritis was 5.9%, 4.0% and 4.0%, respectively. The incidence of febrile morbidity was 5.9%, 2.0% and 6.1%, respectively. These differences are not statistically significant. The single perioperative dose of mezlocillin was as effective as the three-dose regimen of either mezlocillin or cefoxitin.", "The effectiveness of a single prophylactic dose of two broad spectrum antibiotics, during Caesarean section, was compared and evaluated. In 119 consecutive cases at the Cantonal Hospital in Winterthur, Switzerland, either 1 g i.v. cefotaxime or 1,2 g amoxicillin plus clavulanic acid were administered after clamping the umbilical cord during Caesarean section. The study shows that single dose prophylaxis of either regimen provides adequate cover in preventing morbidity in Caesarean section, in both high-risk and low-risk groups.", "The purpose of this present study was to determine whether intraoperative antibiotic uterine irrigation was effective in reducing febrile morbidity (Part 1), and to determine whether ticarcillin disodium (Ticar) or cefoxitin sodium (Mefoxin) was the more effective solution (Part 2). The indications for cesarean section had an effect on febrile morbidity. In patients having nonelective cesarean section, febrile morbidity was high, occurring in 62.7% of the saline control group and 32.9% of those receiving ticarcillin disodium irrigation. In patients having elective cesarean section, febrile morbidity was lower (28% in the saline control group and 8.3% in the ticarcillin group [P less than or equal to .05]). Ticarcillin and cefoxitin were equal in reducing postoperative febrile morbidity. The use of prophylactic antibiotics, therefore, is indicated both in high-risk patients having nonelective cesarean section and in low-risk patients having elective repeat cesarean section.", "Seven antibiotics, administered in 10 different regimens for prophylaxis, were randomly assigned to 1580 patients who were delivered by cesarean section. Cefazolin 1 gm, administered for three doses, served as the control group. Cefazolin 1 gm, cefazolin 2 gm, cefoxitin 1 gm, cefoxitin 2 gm, cefonicid 1 gm, cefotetan 1 gm, ceftizoxime 1 gm, ampicillin 2 gm, and piperacillin 4 gm were all administered in a single dose. Four antibiotics proved to be superior in preventing postpartum endometritis: ampicillin 2 gm (p = 0.03), cefazolin 2 gm (p = 0.005), piperacillin 4 gm (p = 0.0007), and cefotetan 1 gm (p = 0.0001). Single-dose cephalosporin antibiotic prophylaxis was found to result in approximately a twofold increase in Enterococcus faecalis colonization of the vagina (p less than 0.01). This may be significant in patients in whom postpartum endometritis develops and who have failure of initial treatment with a broad-spectrum cephalosporin, e.g., cefoxitin or cefotetan, or a combination such as clindamycin or metronidazole plus an aminoglycoside. Rupture of amniotic membranes for a half hour or more was associated with an increased risk for postpartum endometritis. The use of internal fetal monitoring was associated with an increased risk of soft tissue pelvic infection.", "We carried out a prospective, randomized, controlled clinical trial to evaluate the clinical efficacy of ceftriaxone and ampicillin/cloxacillin prophylaxis in decreasing the frequency of post-caesarean section infection-related morbidity. Two hundred patients randomly received either ceftriaxone (single dose) or ampicillin/cloxacillin (3 doses) intravenously at induction of anaesthesia. There was no statistical difference in incidence of endometritis (P = 0.34), wound infection (P = 0.44), or other febrile morbidity (P = 0.5). Eleven babies had a low Apgar score (< 8) in the ceftriaxone group and 13 in the ampicillin/cloxacillin group (P = 0.82). There were 2 perinatal deaths in each group. One dose of ceftriaxone was as effective as ampicillin/ cloxacillin in preventing post-caesarean section complications and is easier to administer.", "nan", "Cefotaxime, a new third-generation cephalosporin, was compared with ampicillin and cefazolin in a randomized double-blind trial to evaluate the efficacy of antibiotic prophylaxis of febrile morbidity associated with emergency cesarean sections. A 1-gm intravenous dose of one of the three antibiotics was given by bolus injection immediately after clamping of the umbilical cord and six and 12 hours later. All patients were in labor with membranes ruptured and had a temperature less than or equal to 37.8 C, and none had a history of penicillin or cephalosporin allergy. A total of 195 women were entered into the trial. Initially, the study included a placebo control group which was switched to ampicillin after 30 patients. Of the 188 evaluable patients, 51 of 59 (86.5%) ampicillin recipients, 59 of 67 (88.1%) cefazolin recipients, 48 of 55 (87.3%) cefotaxime recipients, and two of seven (28.5%) placebo recipients had uneventful postoperative courses. During the study, an additional 39 women who were in labor with ruptured membranes but who were allergic to penicillin or who declined antibiotic prophylaxis were classified as untreated patients and observed for postoperative complications. Standard febrile morbidity, primarily related to endometritis or wound infections, occurred in 6 of 59 (10.1%) ampicillin, 5 of 67 (7.5%) cefazolin, 5 of 55 (9.1%) cefotaxime, and 18 (40.0%) of placebo or untreated patients. Cefotaxime, cefazolin, and ampicillin were equally effective in reducing febrile morbidity in emergency cesarean sections." ]

[ "6387560", "7312235", "6829919", "12580236", "9033244", "6353840", "6353838", "16167911", "5817847", "3051873" ]

[ "Submucous paracervical blockade compared with intramuscular meperidine as analgesia during labor: a double-blind study.", "Spacing the injection interval with paracervical block: a randomized study.", "Comparison of lidocaine and 2-chloroprocaine in paracervical block: clinical effects and drug concentrations in mother and child.", "Neonatal monitoring after maternal fentanyl analgesia in labor.", "Effective obstetric paracervical block with reduced dose of bupivacaine. A prospective randomized double-blind study comparing 25 mg (0.25%) and 12.5 mg (0.125%) of bupivacaine.", "Which local anesthetic is best suited for paracervical blocks?", "Obstetrical paracervical block with chloroprocaine or bupivacaine. A comparison.", "A comparative study of the safety of 0.25% levobupivacaine and 0.25% racemic bupivacaine for paracervical block in the first stage of labor.", "Marcaine for paracervical anesthesia during labor.", "Pudendal block in vaginal deliveries. Mepivacaine with and without epinephrine." ]

[ "A double-blind study was carried out to compare the effect of submucous paracervical blockade using 12 mL 0.25% bupivacaine (55 women) to the effect of intramuscular injection of 75 mg meperidine (62 women) during the first stage of labor. All 117 were normal primiparous pregnancies. Seventy-eight percent of the women in the paracervical blockade group achieved full or acceptable pain relief against 31% in the meperidine group (P less than .01). Transient fetal bradycardia occurred in two cases in the paracervical blockade group and one in the meperidine group; all infants were born in good condition. Fetal distress, defined as an umbilical artery pH of 7.15 or less and/or a one-minute Apgar score of 7 or less was more frequent in the meperidine group (16 infants) than in the paracervical blockade group (six infants) (P less than .05). Submucous paracervical blockade is superior to intramuscular meperidine as pain relief during labor. Furthermore, meperidine results in more infants with asphyxia as compared with paracervical blockade.", "To test the hypothesis that spacing the injection interval by 10 minutes would reduce the incidence of post-paracervical block bradycardia, 42 healthy subjects at low risk with normal fetal heart rate (FHR) patterns were included in a randomized trial. Twenty patients were given a conventional paracervical block (ie, almost simultaneous injection of the 2 sides), whereas 22 patients were given the second injection after a 10-minute interval. All patients were laterally positioned for 30 minutes before and 60 minutes after administration of the paracervical block. There were no cases of post-paracervical block bradycardia in either group, but a decrease in the baseline FHR of 5 beats per minute or more occurred in one half of each group. Both groups experienced significant decreases in the mean FHR. The authors conclude that patient selection and perhaps lateral positioning are more important than is spacing the injection interval. Furthermore, in properly selected subjects paracervical block offers simple, effective, and safe analgesia.", "2-Chloroprocaine (CP) has recently been recommended as a less toxic alternative to amide-type local anesthetics due to its rapid metabolism. A double-blind, randomized study comparing CP to lidocaine when used for paracervical block was carried out. Twenty-nine patients received CP, while 31 received lidocaine. None of the 60 mothers developed adverse side effects. Adequate pain relief was achieved in 28 cases in each group, with a mean duration of 40 min regardless of the anesthetic. No change in uterine activity was observed. In the CP group one fetus had mild bradycardia, while two in the lidocaine group had severe, and three mild bradycardia within 5-7 min after the block. Low concentrations of CP were detected in the venous blood of 2 of 29 mothers and in the umbilical venous blood of their babies. Measurable amounts of its metabolite, 2-chloro-4-aminobenzoic acid (CABA), were found in all 13 samples of maternal blood 5 min after PCB and in 6 of 27 maternal samples at birth. Traces of CABA were found in umbilical venous blood in three neonates; in a fourth, a level of 1,000 ng/ml was found. In contrast, unmetabolized lidocaine was found in all maternal samples and in all but one of the cord samples at birth. Concentration of lidocaine in cord blood at delivery ranged from less than 100 to 4,000 ng/ml and were similar for both arterial and venous samples. No correlation could be demonstrated between levels of local anesthetics in the cord samples and the frequency or severity of fetal bradycardia regardless of the anesthetic.", "To characterize different methods of monitoring neonatal effects associated with maternal opioid analgesia. Special focus was on the static-charge-sensitive bed (SCSB), which could potentially serve as a non-invasive neonatal monitor.\n 12 healthy, term newborns from normal pregnancies were included in this prospective, randomized, controlled study. Maternal labor analgesia was either intravenous fentanyl (n = 5) or paracervical bupivacaine blockade (n = 7). Neonatal recording from delivery to the age of 12 hours included continuous SCSB monitoring with ECG and oximeter for sleep states, respiration, oxygenation, heart rate, and body movements. In addition, umbilical blood pH, Apgar, Amiel-Tison's Neurologic and Adaptive Capacity Scoring (NACS), skin cyanosis scoring, blood pressure, rectal and skin temperatures, and skin blood flow measurements were performed.\n The study was interrupted, because one baby in the fentanyl group had a significant decrease in oxyhemoglobin saturation (SpO2) to 59%. This was considcred to be residual effect of fentanyl and was treated with naloxone. SpO2 was generally lower in the fentanyl group. Epochs with SpO2 < 90% were more frequent in the fentanyl group, especially during active sleep (mean +/- SD 11.9 +/- 10.7% vs. 2.0 +/- 1.7% of epochs, p = 0.034). Mean heart rate values were lower in the fentanyl group (121.1 +/- 6.4 vs. 132.6 +/- 6.8 beats per minute, p = 0.02), and this difference was seen during wake and all sleep states. Maximum heart rate values were lower in the fentanyl group, too. The opiate group had less quiet sleep than controls (9.6 +/- 2.8% vs. 18.3 +/- 8.3%, p = 0.05). NACS after birth was lower in the fentanyl group (median [range] 15 [13-26] vs. 22 [20-25], p = 0.004).\n Several differences were seen between the fentanyl and the control group babies. The SCSB method proved sensitive enough to find neonatal effects of maternal analgesia. Together with ECG and SpO2 monitoring, SCSB gives plentiful information on neonatal well-being in a non-invasive way. Results of this study emphasize the importance of neonatal monitoring after maternal opiate use in labor.", "To study whether paracervical block (PCB) with 12.5 mg (0.125%) of bupivacaine is as effective as with 25 mg (0.25%) and if there are differences in fetal heart rate (FHR) patterns between the doses.\n A prospective, randomized double-blind study. Fifty-two patients received PCB with 25 mg and 45 patients with 12.5 mg of bupivacaine. Pain intensity was assessed by the patients on a horizontal visual analog scale (VAS). Fetal heart rates of the fetuses were analyzed visually concerning basal rate, variability, accelerations, bradycardia, silent pattern and decelerations.\n The pain relief was statistically significant in both groups up to 120 min after PCB. The VAS-values were similar in both groups both before and after PCB. Fetal heart rate changes appeared in both groups more frequently after than prior to PCB. In patients receiving 25 mg of bupivacaine there appeared to be more FHR changes than in those receiving 12.5 mg.\n Paracervical block with 12.5 mg of bupivacaine is an effective method to relieve pain during labor. Fetal heart rate changes seemed to appear less frequently with this reduced dose. It seems that by lowering the dose of bupivacaine it is possible to reduce fetal side-effects without losing analgesic effect.", "In a prospective, randomized study the duration and effectiveness of four different regimens of PCB were studied: Bupivacaine both with and without adrenaline, and chloroprocaine with and without adrenaline. The pain relief was immediate and almost complete in most patients in all four treatment groups. The duration of the effect of bupivacaine was the same whether adrenaline was added or not. The labors were significantly prolonged with adrenaline, however. The duration of the effect of chloroprocaine was substantially shorter than bupivacaine, but with this short-lasting anesthetic the duration was prolonged by the addition of adrenaline. It is concluded that bupivacaine without the addition of adrenaline is the drug of choice for PCB.", "Obstetrical paracervical block was randomly administered to 47 patients, using either 2% chloroprocaine or 0.25% bupivacaine. Analgesia and onset of analgesia were similar for both drugs, but the duration of chloroprocaine was only about half that of bupivacaine (35 min versus 66 min). Fetal bradycardia was encountered in one case after chloroprocaine and in two cases after bupivacaine. It is concluded that chloroprocaine plain is not very suitable for obstetrical paracervical block due to its short duration of action.", "The objective of the study was to evaluate and compare the safety of levobupivacaine and racemic bupivacaine for paracervical block (PCB) in the first stage of labor after uncomplicated pregnancy.\n Forty women in an open pilot study and 397 women in a double-blind randomized study received PCB for pain relief in the first stage of labor, either with 25 mg of levobupivacaine or with 25 mg of racemic bupivacaine. The incidence of cardiotocographic pathology was compared between the groups using Fisher's exact test. The 95% confidence intervals for the between-group difference were calculated by Newcombe's method.\n In the randomized double-blind study, the incidence of any pathological result in cardiotocography (CTG) was 10.4% in the levobupivacaine group and 12.8% in the racemic bupivacaine group. The incidence of fetal bradycardia in the groups was 2.6 and 3.8%, respectively. All the cardiotocographic changes were transient, and no operative intervention was indicated because of CTG. No difference in the analgesic effect between the drugs was found. Most of the parturients in the levobupivacaine group (97%) and in the racemic bupivacaine group (96%) had spontaneous vaginal delivery. Neonatal outcome was good in both groups.\n No difference in cardiotocographic pathology was found between PCB with levobupivacaine compared with PCB with racemic bupivacaine. The incidence of bradycardia was low. PCB was found to be a safe pain-relief method for low-risk parturients.", "nan", "Pudendal block with 20 ml 1% mepivacaine with and without epinephrine was performed in 151 patients during the second stage of labor. No differences in efficacy of the block or in Apgar scores between the two groups were found. The maternal mepivacaine concentration was higher in the plain group than in the epinephrine group (p less than 0.01), but toxic levels were never reached. In the infants, no difference in mepivacaine concentration was found between the groups (p greater than 0.05, type II error 9%) and toxic levels were not reached. The time elapsed from the pudendal block until delivery was prolonged when epinephrine was added (p less than 0.02). We found no effect on blood pressure in either of the groups, with or without oxytocin and/or methergin. Twenty ml 1% mepivacaine (plain) is a safe choice for pudendal block without the possible disadvantages of adding epinephrine." ]

[ "3044868", "3552457" ]

[ "Analgesic effect of aspirin, mefenamic acid and their combination in post-operative oral surgery pain.", "Comparison of two formulations of lignocaine spray with mefenamic acid in the relief of post-episiotomy pain: a placebo-controlled study." ]

[ "A double-blind randomized single dose study of the analgesic effects of 650 mg aspirin, 250 mg mefenamic acid, the combination of 650 mg aspirin and 250 mg mefenamic acid and placebo on 120 patients with pain following oral surgery was conducted. Patients evaluated their pain intensity and extent of pain relief at 1, 2, 3 and 4 h after drug administration. For most parameters, including the sum of the pain intensity differences and the sum of the hourly pain relief scores, each of the drugs was more effective than placebo. Aspirin-mefenamic acid in combination was more effective than both drugs alone, and aspirin and mefenamic acid alone were equally effective for most of the analgesic variables.", "The analgesic effectiveness of aqueous and alcoholic formulations of lignocaine (5%) spray was compared with that of mefenamic acid (500 mg) or placebo in a double-blind study in 103 primiparous patients complaining of moderate or severe perineal pain associated with episiotomy. The results, assessed after a single dose, showed that the aqueous lignocaine formulation provided a level of pain relief superior to that obtained with the alcoholic formulation or placebo, and similar to that obtained with mefenamic acid." ]

[ "7710151", "12362006", "10092916", "21125215", "2569600" ]

[ "Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen.", "Hyperbaric oxygen for acute carbon monoxide poisoning.", "Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial.", "Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials.", "Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication." ]

[ "Carbon monoxide (CO) poisoning is a major clinical problem. The risk of morbidity and the most effective treatment have not been clearly established. We measured the incidence of delayed neurologic sequelae (DNS) in a group of patients acutely poisoned with CO and tested the null hypothesis that the incidence would not be affected by treatment with hyperbaric oxygen (HBO).\n We conducted a prospective, randomized study in patients with mild to moderate CO poisoning who presented within 6 hours. Patients had no history of loss of consciousness or cardiac instability.\n The incidence of DNS was compared between groups treated with ambient pressure 100% oxygen or HBO (2.8 ATA for 30 minutes followed by 2.0 ATA oxygen for 90 minutes). DNS were defined as development of new symptoms after oxygen treatment plus deterioration on one or more subtests of a standardized neuropsychologic screening battery.\n In 7 of 30 patients (23%), DNS developed after treatment with ambient-pressure oxygen, whereas no sequelae developed in 30 patients after HBO treatment (P < .05). DNS occurred 6 +/- 1 (mean +/- SE) days after poisoning and persisted 41 +/- 8 days. At follow-up 4 weeks after poisoning, patients who had been treated with ambient pressure oxygen and had not sustained DNS exhibited a worse mean score on one subtest, Trail Making, compared with the group treated with HBO and with a control group matched according to age and education level. There were no differences in scores between the control group and the hyperbaric oxygen group.\n DNS after CO poisoning cannot be predicted on the basis of a patient's clinical history or CO level. HBO treatment decreased the incidence of DNS after CO poisoning.", "Patients with acute carbon monoxide poisoning commonly have cognitive sequelae. We conducted a double-blind, randomized trial to evaluate the effect of hyperbaric-oxygen treatment on such cognitive sequelae.\n We randomly assigned patients with symptomatic acute carbon monoxide poisoning in equal proportions to three chamber sessions within a 24-hour period, consisting of either three hyperbaric-oxygen treatments or one normobaric-oxygen treatment plus two sessions of exposure to normobaric room air. Oxygen treatments were administered from a high-flow reservoir through a face mask that prevented rebreathing or by endotracheal tube. Neuropsychological tests were administered immediately after chamber sessions 1 and 3, and 2 weeks, 6 weeks, 6 months, and 12 months after enrollment. The primary outcome was cognitive sequelae six weeks after carbon monoxide poisoning.\n The trial was stopped after the third of four scheduled interim analyses, at which point there were 76 patients in each group. Cognitive sequelae at six weeks were less frequent in the hyperbaric-oxygen group (19 of 76 [25.0 percent]) than in the normobaric-oxygen group (35 of 76 [46.1 percent], P=0.007), even after adjustment for cerebellar dysfunction and for stratification variables (adjusted odds ratio, 0.45 [95 percent confidence interval, 0.22 to 0.92]; P=0.03). The presence of cerebellar dysfunction before treatment was associated with the occurrence of cognitive sequelae (odds ratio, 5.71 [95 percent confidence interval, 1.69 to 19.31]; P=0.005) and was more frequent in the normobaric-oxygen group (15 percent vs. 4 percent, P=0.03). Cognitive sequelae were less frequent in the hyperbaric-oxygen group at 12 months, according to the intention-to-treat analysis (P=0.04).\n Three hyperbaric-oxygen treatments within a 24-hour period appeared to reduce the risk of cognitive sequelae 6 weeks and 12 months after acute carbon monoxide poisoning.\n Copyright 2002 Massachusetts Medical Society", "To assess neurological sequelae in patients with all grades of carbon monoxide (CO) poisoning after treatment with hyperbaric oxygen (HBO) and normobaric oxygen (NBO).\n Randomised controlled double-blind trial, including an extended series of neuropsychological tests and sham treatments in a multiplace hyperbaric chamber for patients treated with NBO.\n The multiplace hyperbaric chamber at the Alfred Hospital, a university-attached quarternary referral centre in Melbourne providing the only hyperbaric service in the State of Victoria.\n All patients referred with CO poisoning between 1 September 1993 and 30 December 1995, irrespective of severity of poisoning. Pregnant women, children, burns victims and those refusing consent were excluded.\n Daily 100-minute treatments with 100% oxygen in a hyperbaric chamber--60 minutes at 2.8 atmospheres absolute for the HBO group and at 1.0 atmosphere absolute for the NBO group--for three days (or for six days for patients who were clinically abnormal or had poor neuropsychological outcome after three treatments). Both groups received continuous high flow oxygen between treatments.\n Neuropsychological performance at completion of treatment, and at one month where possible.\n More patients in the HBO group required additional treatments (28% v. 15%, P = 0.01 for all patients; 35% v. 13%, P = 0.001 for severely poisoned patients). HBO patients had a worse outcome in the learning test at completion of treatment (P = 0.01 for all patients; P = 0.005 for severely poisoned patients) and a greater number of abnormal test results at completion of treatment (P = 0.02 for all patients; P = 0.008 for severely poisoned patients). A greater percentage of severely poisoned patients in the HBO group had a poor outcome at completion of treatment (P = 0.03). Delayed neurological sequelae were restricted to HBO patients (P = 0.03). No outcome measure was worse in the NBO group.\n In this trial, in which both groups received high doses of oxygen, HBO therapy did not benefit, and may have worsened, the outcome. We cannot recommend its use in CO poisoning.", "Although hyperbaric oxygen therapy (HBO) is broadly used for carbon monoxide (CO) poisoning, its efficacy and practical modalities remain controversial.\n To assess HBO in patients poisoned with CO.\n Two prospective randomized trial on two parallel groups.\n Critical Care Unit, Raymond Poincaré Hospital, Garches, France.\n Three hundred eighty-five patients with acute domestic CO poisoning.\n Patients with transient loss of consciousness (trial A, n = 179) were randomized to either 6 h of normobaric oxygen therapy (NBO; arm A0, n = 86) or 4 h of NBO plus one HBO session (arm A1, n = 93). Patients with initial coma (trial B, n = 206) were randomized to either 4 h of NBO plus one HBO session (arm B1, n = 101) or 4 h of NBO plus two 2 HBO sessions (arm B2, n = 105). PRIMARY ENDPOINT: Proportion of patients with complete recovery at 1 month.\n In trial A, there was no evidence for a difference in 1-month complete recovery rates with and without HBO [58% compared to 61%; unadjusted odds ratio, 0.90 (95% CI, 0.47-1.71)]. In trial B, complete recovery rates were significantly lower with two than with one HBO session [47% compared to 68%; unadjusted odds ratio, 0.42 (CI, 0.23-0.79)].\n In patients with transient loss of consciousness, there was no evidence of superiority of HBO over NBO. In comatose patients, two HBO sessions were associated with worse outcomes than one HBO session.", "The value of hyperbaric oxygen in the treatment of acute carbon monoxide intoxication was assessed in 629 adults who had been poisoned at home in the 12 h before admission to hospital. In patients without initial impairment of consciousness (group A) the effect of 6 h of normobaric oxygen (NBO) (group A0, n = 170) was compared with that of 2 h of hyperbaric oxygen (HBO) at 2 atmospheres absolute (ATA) plus 4 h NBO (group A1, n = 173). At the 1 month follow-up 66% of A0 and 68% of A1 patients had recovered. In patients with initial impairment of consciousness the effect of one session of HBO (group B1, n = 145) was compared with that of two sessions (group B2, n = 141); all group B patients also received 4 h of NBO. At 1 month of follow-up 54% group B1 and 52% group B2 patients had recovered. The 7 patients left with neuropsychiatric sequelae (3 B1, 4 B2) and the 4 who died (2 B1, 2 B2) had all presented with coma. HBO was not useful in patients who did not lose consciousness during carbon monoxide intoxication, irrespective of their carboxyhaemoglobin level, nor were two sessions of HBO in patients who sustained only a brief loss of consciousness. The prognosis is poorest for those presenting with coma; the trial needs to be pursued in this group of patients until the power of the study is sufficient to demonstrate the value or otherwise of HBO." ]

[ "14722370", "18641196", "12736400", "11123827", "11451725", "12003652", "11424510", "11814373", "15164114", "16603147", "10721929", "17928808", "10989766", "9209187", "19652922", "11890637", "10633202" ]

[ "Efficacy of twice weekly iron supplementation in anemic adolescent girls.", "Weekly may be as efficacious as daily folic acid supplementation in improving folate status and lowering serum homocysteine concentrations in Guatemalan women.", "Anemia prophylaxis in adolescent school girls by weekly or daily iron-folate supplementation.", "The impact of weekly iron supplementation on the iron status and growth of adolescent girls in Tanzania.", "Concomitant supplemental vitamin A enhances the response to weekly supplemental iron and folic acid in anemic teenagers in urban Bangladesh.", "A randomised trial in Mali of the effectiveness of weekly iron supplements given by teachers on the haemoglobin concentrations of schoolchildren.", "The effect of weekly iron supplementation on anaemia and on iron deficiency among female tea pluckers in Bangladesh.", "Weekly vs daily iron and folic acid supplementation in adolescent Nepalese girls.", "Effectiveness of weekly vitamin A (10,000 IU) and iron (60 mg) supplementation for adolescent boys and girls through schools in rural and urban East Java, Indonesia.", "Effect of daily versus twice weekly long-term iron supplementation on iron absorption and status in iron-deficient women: a stable isotope study.", "Efficacy and acceptability of two iron supplementation schedules in adolescent school girls in Lima, Peru.", "The effect of weekly iron and vitamin A supplementation on hemoglobin levels and iron status in adolescent schoolgirls in western Kenya.", "Effect of daily and intermittent iron supplementation on iron status of high school girls.", "Weekly micronutrient supplementation to build iron stores in female Indonesian adolescents.", "Once weekly low-dose iron supplementation effectively improved iron status in adolescent girls.", "Will iron supplementation given during menstruation improve iron status better than weekly supplementation?", "[Use of daily and weekly ferrous sulfate to treat anemic childbearing-age women]." ]

[ "Two hundred and forty four girls with different hemoglobin levels were selected, of which forty-one were non-anemic. The rest were graded as mildly, moderately or severely anemic and supplemented with 60 mg of iron daily or twice weekly for twelve weeks. There was no significant difference in the increase in hemoglobin levels between daily and twice weekly-supplemented subjects at the end of the study. Unpleasant side effects of supplementation were experienced by 57.8% of the daily supplemented subjects as against 5.9% of twice weekly-supplemented ones. Twice weekly supplementation could be recommended for overcoming anemia in adolescent girls.", "Daily folic acid (FA) supplementation improves folate status, lowers circulating homocysteine (Hcy) concentrations, and reduces the risk of neural tube defects. Little is known about the efficacy of weekly FA supplementation. The objective of this study was to compare the efficacy of weekly and daily FA supplementations in improving folate and vitamin B-12 status and lowering Hcy concentrations in healthy reproductive-aged women. A randomized, double-blind supplementation trial was conducted in Guatemala. A total of 459 women were assigned randomly to 4 groups to receive weekly (5000 or 2800 microg) or daily (400 or 200 microg) FA for 12 wk. Daily and weekly iron, zinc, and vitamin B-12 were also provided. We determined serum and RBC folate by microbiological assays, but the latter was available only at baseline. Serum Hcy and vitamin B-12 were also measured. We used generalized linear regression models to assess the effects of treatment on biochemical indicators. Supplementation improved folate status similarly across all 4 groups. Overall, mean serum folate concentrations increased by 15.4 nmol/L (95% CI: 13.8, 16.9) and the geometric mean serum Hcy concentration decreased by 9.8% (95% CI: -12.3, -7.1). Daily supplementation improved serum vitamin B-12 by 20% (95% CI: 8, 33.2), whereas weekly supplementation had no effect. In conclusion, weekly FA (either high or low dose) plus vitamin B-12 may be as efficacious as daily supplementation in improving serum folate and lowering Hcy concentrations in healthy women of reproductive age.", "To examine the benefits of anemia prophylaxis in adolescent school.girls by weekly or daily iron-folate supplementation.\n Prospective study.\n Government girl schools of northeast Delhi.\n 2088 subjects (with hemoglobin greater than 7.9 g/dL), including 702 on daily and 695 on weekly iron-folate administration; 691 girls served as controls.\n About 85% girls were iron deficient out of which 49.3% were anemic. Weekly administration took longer time to raise hemoglobin but was effective as well as practical. Plasma ferritin estimation in girls showed rise in level in both the treated groups.\n Weekly administration of iron-folate was a practical and effective strategy for anemia prophylaxis in adolescent school girls.", "We evaluated the effect of weekly doses of 400 mg of ferrous sulphate for 4 months on the iron status of adolescent girls in a controlled trial in Tanga, Tanzania. Supplementation led to a significantly greater increase in serum ferritin compared with the control group (+ 15.6 microg/l vs. 8.6 microg/l) (P = 0.002) but there was no significant difference in change in haemoglobin. Children given iron showed a significantly greater weight gain than controls (+ 2.4 kg vs. + 1.4 kg) (P = 0.03). Weekly iron supplementation may be an effective means of increasing iron stores and growth in children vulnerable to iron deficiency.", "Iron deficiency is the most common micronutrient deficiency and affects >2 billion persons worldwide, leading to anemia in >40% of women of reproductive age in the developing world.\n The objective was to determine whether weekly supplementation with iron and folate would reduce the frequency of anemia in teenage women in urban Bangladesh before they became pregnant.\n Participants with a hemoglobin concentration of 80-120 g/L were entered into a randomized, double-blind, placebo-controlled trial and received supplements of placebo, vitamin A, iron + folic acid, or iron + folic acid + vitamin A weekly for 12 wk. The supplements contained 2.42 mg vitamin A (retinol) as retinyl palmitate, 120 mg elemental Fe as ferrous sulfate, and 3.5 mg folic acid.\n Hemoglobin concentrations increased significantly more after supplementation with iron + folic acid or iron + folic acid + vitamin A than after either the placebo or vitamin A alone. There was a significantly greater increase in hemoglobin after iron + folic acid + vitamin A than after iron + folic acid, but the additional effect disappeared after adjustment for baseline hemoglobin, serum vitamin A, and ferritin and the number of supplements taken. Those with the lowest baseline hemoglobin had the greatest increase in hemoglobin. Compared with the placebo, iron + folic acid + vitamin A reduced anemia by 92%, iron deficiency by 90%, and vitamin A deficiency by 76%.\n There may be significant health benefits from a program that enhances the nutritional status of iron, folate, and vitamin A in poor urban young women before they become pregnant.", "To assess the effect on the haemoglobin concentrations of schoolchildren of weekly iron tablets administered by teachers.\n Sixty schools were randomly assigned to two groups: in 30 schools children were given weekly for 10 weeks a tablet providing 65 mg of iron and 0.25 mg of folic acid; in the other 30 schools no iron tablets were given. All children were dewormed and given vitamin A before the study began. The haemoglobin concentration of up to 20 randomly selected children in each school was estimated before and 2 weeks after the end of treatment.\n Rural community schools in Kolondieba district of Mali.\n Some 1113 schoolchildren aged 6-19 years with a mean of 11.4 years.\n The haemoglobin concentration of treated children rose on average by 1.8 g l(-1) and the prevalence of anaemia fell by 8.2%; in untreated children the haemoglobin concentration fell by an average of -2.7 g l(-1) and the prevalence of anaemia rose by 9.4%. The fall in haemoglobin concentration among untreated girls of -4.0 g l(-1) was greater than in untreated boys (-0.3 g l(-1) ).\n Weekly iron tablets given by teachers prevented a general fall in the haemoglobin concentrations of untreated children, and led to a small but statistically significant rise among treated children. Young children benefited more than children aged >or=12 years, and girls benefited more than boys.", "To investigate the effect of weekly iron supplementation on anaemia and iron deficiency among adult, female tea pluckers.\n A randomized double-blind intervention trial was conducted in a tea estate in Bangladesh where a total of 280 women received either weekly iron supplementation (200 mg ferrous fumarate and 200 mg folic acid) for 24 weeks or a matching placebo. Capillary blood samples were drawn at baseline and post-trial to determine haemoglobin, haematocrit and ferritin concentration. Mean corpuscular haemoglobin concentration (MCHC) was calculated using the haemoglobin and haematocrit values.\n The mean haemoglobin concentration in the supplemented group increased by 5.52 g L-1 over the study period, on average, while ferritin values decreased by 0.33 microgram L-1. The control group showed a decrease in both mean haemoglobin (-0.24 g L-1) and ferritin (-5.32 micrograms L-1). Those individuals in the supplemented group with the lowest pretrial haemoglobin and ferritin values experienced the greatest improvements post-trial, whereas nonanaemic individuals showed a decrease in both haemoglobin and ferritin concentrations. A total of 62.2% of women in the supplemented group reported feeling better and more energetic compared to 51.1% in the placebo group; 14.4% of the supplemented group and 22.7% of the control group complained about side-effects.\n Weekly iron supplementation was logistically simpler and cheaper than daily supplementation but would have to be continued on a longer term basis in order to combat both anaemia and iron deficiency.", "To compare the effectiveness of weekly vs daily iron and folic acid supplementation for control of anemia in adolescent Nepalese girls.\n Randomized controlled trial.\n A Government Girl School in Dharan, Nepal, an urban foothill town that is 305 m above sea level.\n Consecutive healthy adolescent girls (n = 209, median age 15 years) randomized to 3 groups matched for age, anthropometry, and personal and sociodemographic characteristics. Of 209 subjects, 181 completed the trial. Two girls had adverse reactions to treatment and were excluded.\n Group A (n = 70) received a 350-mg ferrous sulfate and 1.5-mg folic acid combination once daily for 90 to 100 days. Group B (n = 67) received the tablet under supervision once a week for 14 weeks. Group C (n = 72) did not receive any drugs.\n Presupplementation and postsupplementation differences in prevalence of anemia and change in hematocrit.\n Prevalence of anemia (defined as hematocrit <36%) declined from 68.6% and 70.1% in groups A and B to 20% and 13.4%, respectively, postsupplementation (P<.001), whereas the prevalence in group C changed little (68.1% to 65.3%, P =.81). There was a significant rise in the mean hematocrit of both supplemented groups (group A, 32.9% +/- 3.5% to 41.0% +/- 5.6%, P<.001; group B, 33.2% +/- 3.6% to 40.4% +/- 4.9%, P<.001) but no appreciable change in controls (34.2% +/- 2.9% to 34.1% +/- 3.3%, P =.91). Net change in mean hematocrit in both the supplementation groups was comparable (P =.57).\n The prevalence of anemia in adolescent Nepalese girls is high. Supervised iron and folic acid therapy once a week is an effective alternative to daily administration and helps lower the prevalence of anemia in adolescent girls.", "High prevalences of vitamin A deficiency and anaemia among adolescents warrant interventions. This study evaluated the effectiveness of school-based supplementation to reduce anaemia and improve vitamin A status.\n School-based, grade-randomized, intervention.\n In all, 1757 girls and 1859 boys, aged 12-15 y, in 24 Junior High Schools.\n Weekly supplementation for 14 weeks with 60 mg iron and 250 microg folate (Fe group; n=978), 10 000 IU vitamin A (VA group; n=970) or both (VAFe group; n=1042) to subjects in 15 schools, compared to subjects in nine other schools not receiving supplements (control; n=626).\n The baseline anaemia prevalence (Hb <120 g/l) in girls was 20% (prepubertal) and 26% (pubertal), and in boys 24% (pre-pubertal) and 11% (pubertal). Serum retinol concentrations were low (<1.05 micromol/l) in 41% of boys and 45% of girls. The interventions did not increase haemoglobin concentrations. Serum retinol concentration of boys, but not girls, in the VA group increased (0.33 vs 0.07 micromol/l in controls; P<0.01). The risk factors for low serum retinol concentration were lower baseline serum retinol concentration (OR 0.02-0.03) with, for girls, nightblindness at baseline (OR 5.88), and for boys, not receiving vitamin A (OR control: 1.00; VA: 0.37; Fe: 0.77; VAFe: 0.34) and maternal illiteracy (OR mother never attended school 1.00, mother received any formal education 0.17-0.33).\n Supplementation with vitamin A increased serum retinol concentration of boys. Iron supplementation did not change Hb. This appeared to be due to poor compliance, and partly related to side effects.", "This work aims at studying the effect of daily versus twice weekly long-term Fe supplementation on Fe absorption and status in Fe-deficient women.\n The study design is a randomized controlled open study carried out in the Internal Medicine Department, CHU de Clermont-Ferrand, France. Twenty-four young women participated in this study and were randomized into two groups: Group 1 received 50 mg Fe daily, and group 2 received 50 mg Fe twice weekly for 3 months. On day 10 (D10) and on day 90 (D90) of Fe supplementation, blood samples were obtained, and women received orally about 5 mg of 57Fe, and blood was sampled at different times over 24 h. The 57Fe absorption was evaluated by calculating the areas under the curves (AUC). Fe and oxidative stress status were also assessed.\n 57Fe absorption was similar in both groups on D10 but was greatly decreased in Group 1 and remained high in Group 2 on D90. Fe status was more improved in Group 1 than in Group 2. Oxidative stress status remained statistically unchanged.\n Our study shows that daily Fe supplementation is able to correct an Fe deficiency much more than twice weekly Fe supplementation in young women.", "To assess the efficacy and acceptability of a daily and intermittent iron supplementation, a double-blind, placebo-controlled trial was conducted in a public school located in periurban Lima, Peru. Adolescent girls (n = 312), 12-18 y old, were randomly assigned to one of the following three groups: 1) 60 mg iron as ferrous sulfate daily from Monday to Friday; 2) 60 mg iron as ferrous sulfate 2 d/wk and 3 d placebo (intermittent); 3) placebo, from Monday to Friday. Field workers gave the girls supplements during school hours for 17 wk; 296 girls completed the trial. Girls took 94% of the expected dose of 85 pills. Few side effects were reported. Postintervention, hemoglobin (Hb), serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) were improved significantly in the iron-supplemented groups compared with placebo (P<0.05). Daily supplements led to higher Hb increases than intermittent supplements (P<0.05), but SF and FEP were similar between the two groups. Thus, both iron supplementation schedules were efficacious in preventing iron deficiency in adolescent girls through the school system, and the daily schedule was better than the intermittent schedule at increasing Hb values and reducing anemia.", "Iron deficiency anemia is a major public health problem in developing countries and may affect school performance and physical work capacity in nonpregnant adolescents, and may increase the risk of anemia during subsequent teenage pregnancies. We assessed the effect of weekly iron (120 mg elemental iron) and vitamin A (25 000 IU) supplementation on hemoglobin, iron status and malaria and nonmalaria morbidity in adolescent schoolgirls.\n A total of 279 schoolgirls aged 12-18 years from public primary schools in Kisumu, western Kenya. Double-blind randomized placebo-controlled trial using a factorial design.\n Five months of iron supplementation was associated with a 0.52 g dl(-1) (0.21, 0.82) greater increase in hemoglobin relative to iron placebo. The effect was only observed in girls with iron deficiency on enrollment (1.34 g dl(-1) (0.79, 1.88)), but not in iron-replete girls (-0.20 g dl(-1) (-0.59, 0.18)). Similar differences in treatment effect were seen between menstruating and nonmenstruating girls. The effect of iron was independent of vitamin A. The baseline prevalence of vitamin A deficiency was low (6.7%) and no sustained increase in hemoglobin was seen with weekly vitamin A (-0.07 g dl(-1) (-0.38, 0.25)). Incidence of malaria parasitemia was higher in the iron than iron-placebo groups (Rate ratio 1.33 (0.94, 1.88)).\n Weekly iron supplementation results in substantial increases in hemoglobin concentration in adolescent schoolgirls in western Kenya, which may outweigh possible risks caused by malaria, but only in iron-deficient or menstruating girls and not in iron-replete and nonmenstruating girls.", "This experimental study was designed to investigate the effects of daily versus intermittent iron supplementation on iron status of high school girls in Zahedan and Rasht cities in 1996-1997. The subjects were selected randomly from among students of grades 1-3 of four high schools in each city. Anemia was determined by measuring hematological indices. 260 anemic and a similar number of non-anemic subjects of 4 high schools were selected and allocated randomly to 4 treatment groups. During a 3-month period, the test groups were given 150 mg ferrous sulfate tablets (50 mg Fe). Subjects in group 1 received a daily dose, groups 2 & 3 received twice or once weekly doses respectively. The control group received no iron supplement. For these subjects, in addition to hematological indices biochemical iron indices were measured in the beginning and at the end of the study. The increases in hemoglobin concentration in anemic subjects were not significantly different among supplemented groups but were different from the control group (p < 0.00001). Among anemic subjects, changes in serum ferritin levels in 3 supplemented groups were significantly different from the control group. Serum ferritin in Group 1 was also increased to a greater extent than groups 2 and 3 (P < 0.00001). It is concluded that over the study period a weekly iron dose was as effective as a daily dose in treating anemia but the daily dose was more effective in improving iron stores than a weekly dose in the short run.", "Different supplementation schemes to build iron stores in female Indonesian adolescents were investigated. Subjects were 273 high-school girls allocated randomly to four treatment groups. During a 3-mo period one group received 60 mg Fe, 750 micrograms retinol, 250 micrograms folic acid, and 60 mg vitamin C per day; a second group received 60 mg Fe, 6000 micrograms retinol, 500 mg folic acid, and 60 mg vitamin C once a week; a third group received 120 mg Fe and the same amount of the other three micronutrients as the second group once a week; and a fourth group received only placebos. All subjects were dewormed and supplement allocation was double blind. Blood samples were collected at baseline, after 2 and 3 mo of supplementation, and 6 mo after the last supplement. After 2 mo of supplementation, groups supplemented weekly and daily showed similar significant improvements (P < 0.001) in hemoglobin and retinol concentrations, and supplementation for 3 instead of 2 mo did not significantly increase these two indicators. After 3 mo, the increase in ferritin was approximately equal to 27 micrograms/L in the daily and 14-15 micrograms/L in the weekly groups (P < 0.001), the latter having a final concentration of 42-45 micrograms/L. At 6 mo postsupplementation there were no significant differences among daily and weekly groups, but the ferritin concentration was still approximately equal to 10-12-micrograms/L higher (P < 0.001) than in the placebo group. The group supplemented weekly with 60 mg Fe complained less about side effects than the other supplemented groups (P < 0.05). Weekly supplementation with 60 mg Fe and 6000 micrograms retinol for 3 mo was optimal for improving the iron status of the adolescents for approximately equal to 9 mo.", "Iron supplementation has been suggested as a strategy for prevention and treatment of iron deficiency (ID) and iron deficiency anemia (IDA) in many countries, but non-compliance of daily regimens and common dosage remain as major challenges. The aim of this study was to investigate the effects of low dose once weekly iron supplementation in adolescent girls. The study was designed as a community-based, randomized, supplementation trial. The initial sample consisted of 200 female high school students, aged 14-16 years old, of whom 193 students concluded the study. They were randomly selected and assigned into either iron-supplemented group (ISG) or iron-unsupplemented group (IUG). The ISG received 150 mg ferrous sulfate once weekly for 16 weeks, whereas the IUG received nothing. Weight, height, and hematological parameters were measured and compared between the two groups before and after the intervention. There was no significant difference between the initial measures of the two groups before the intervention. After 16 weeks of intervention, mean of hemoglobin and serum ferritin improved significantly in ISG compared to IUG. At the beginning of the study, percent of anemia, IDA, and ID in ISG were 12.5%, 8.3%, and 30.2%, whereas these figures for IUG in this period of study were 14.4, 10.3, and 38.2, respectively, which were not significantly different between the two groups. However, percentages of the above items at the end of study in ISG were 2.1%, 0%, and 21.9%, respectively. In contrast to IUG, all cases of IDA were abolished in the ISG. Our study showed that once weekly supplementation of 150 mg ferrous sulfate for 16 weeks significantly improved iron status in female adolescents and effectively treated IDA. There is no need for higher dosage of iron for supplementation that may cause adverse effects and bear higher costs.", "To investigate the efficacy of two different iron supplements administered either on a weekly basis or during menstruation, a 16-week community experimental study was carried out among postmenarcheal female adolescent students in Kupang, East Nusa Tenggara, Indonesia. Forty eight students received a placebo tablet weekly, 48 other students got an iron tablet weekly and 41 students took an iron tablet for four consecutive days during their menstruation cycle. All subjects were given deworming tablets before supplementation. Haemoglobin, serum ferritin, height, weight, mid-upper arm circumference and dietary intake were assessed before and after intervention. The supplementation contributed to a significant improvement in the iron status of the intervention groups compared to the placebo group (P < 0.05). In the menstruation group, the haemoglobin concentrations of the anaemic subjects improved significantly (P < 0.05) while for the non-anaemic subjects, serum ferritin concentrations also increased significantly (P < 0.05). In the weekly group for anaemic and nonanaemic subjects, there was a significant increase in both haemoglobin and serum ferritin concentrations (P < 0.05). This study revealed that weekly supplementation of iron tablets continued for 16 weeks contributed a higher improvement to haemoglobin concentration, compared with supplementing iron tablets for four consecutive days during menstruation for four menstrual cycles. This suggests that weekly iron supplementation is preferable.", "A blind randomized trial was conducted in a low-income community in the city of Recife, Pernambuco, Brazil, with 193 anemic (Hb <12 mg/dl) and \"menstruating\" women (age range: 15-45 years) to compare daily and weekly doses of ferrous sulfate (60 mg elemental iron) and treatment compliance. Blood samples were taken from 484 women to determine hemoglobin levels before and after the trial and mean corpuscular volume (MCV) at end of treatment. After 12 weeks' follow-up, 150 women completed the trial, 79 on the alternative weekly regimen and 71 on the conventional daily regimen. Mean corpuscular hemoglobin concentrations (MCHC) prior to treatment were 10.52 g/dl (DP=1.13) and 10.72 g/dl (DP=0.92), respectively, for the alternative and conventional regimens. After the intervention they were 11.83 g/dl (DP=0.97) for the weekly regimen and 11.62 g/dl (DP=1.39) for the daily one. The alternative regimen was better accepted than the conventional one. There was no significant difference (p=0.22) between differences in the mean values of the two regimens, although the cure rate was higher after the alternative treatment. The study concluded that the weekly regimen was no less effective than daily treatment." ]

[ "1935254", "8129407", "2250110", "1428436", "17451383", "12072067", "10674382", "11050579", "19239555", "15034503", "8225725", "17986309", "15057016", "21700360", "17324826", "14996107", "17168873", "12524069" ]

[ "Topical minoxidil in the treatment of androgenetic alopecia in women.", "Androgenetic alopecia in the female. Treatment with 2% topical minoxidil solution.", "Quantitative estimation of hair growth. I. androgenetic alopecia in women: effect of minoxidil.", "Treatment of female androgenetic alopecia with minoxidil 2%.", "Comparison of the efficacy and safety of topical minoxidil and topical alfatradiol in the treatment of androgenetic alopecia in women.", "Effects of minoxidil 2% vs. cyproterone acetate treatment on female androgenetic alopecia: a controlled, 12-month randomized trial.", "Measuring reversal of hair miniaturization in androgenetic alopecia by follicular counts in horizontal sections of serial scalp biopsies: results of finasteride 1 mg treatment of men and postmenopausal women.", "Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia.", "Adenosine increases anagen hair growth and thick hairs in Japanese women with female pattern hair loss: a pilot, double-blind, randomized, placebo-controlled trial.", "A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss.", "Use of topical minoxidil therapy for androgenetic alopecia in women.", "Topical fulvestrant solution has no effect on male and postmenopausal female androgenetic alopecia: results from two randomized, proof-of-concept studies.", "Topical estrogen therapy for androgenetic alopecia in menopausal females.", "A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women.", "A randomized, placebo-controlled trial of 1% topical minoxidil solution in the treatment of androgenetic alopecia in Japanese women.", "Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial.", "A pilot study evaluating the efficacy of topically applied niacin derivatives for treatment of female pattern alopecia.", "Treatment of hyperandrogenic alopecia in women." ]

[ "Twenty-eight women with mild to moderate androgenetic alopecia were randomly assigned to apply either 2 percent topical minoxidil or placebo (vehicle) to their involved scalp areas twice daily. At the end of thirty-two weeks, there was a statistically significant increase of nonvellus target area hairs in the minoxidil-treated versus the vehicle-treated group (p = 0.006). Investigator assessment of moderate regrowth showed better results in subjects who used 2 percent topical minoxidil solution than those who used vehicle (p = 0.007), although subjects discerned no difference between treatment groups. Two percent topical minoxidil appears to be effective in the treatment of female androgenetic alopecia.", "Women generally regard their hair loss as socially unacceptable and go to great measures to conceal their problem. In some cases, the negative self-image brought about by hair loss may be the basis of psychiatric illness. The purpose of this study was to evaluate a 2% topical minoxidil solution (Rogaine/Regaine, The Upjohn Co, Kalamazoo, Mich) for the treatment of female androgenetic alopecia. A 32-week, double-blind, placebo-controlled trial was conducted in 11 US centers. Three hundred eight women with androgenetic alopecia were enrolled. Two hundred fifty-six of these women completed the trial. A refined photographic technique was used to objectively determine the number of nonvellus hairs regrown.\n After 32 weeks of treatment, the number of nonvellus hairs in a 1-cm2 evaluation site was increased by an average of 23 hairs in the 2% minoxidil group and by an average of 11 hairs in the placebo group. The 95% confidence interval for the difference in mean hair count change between the treatment groups was 5.9 to 17.5 hairs. The investigators determined that 13% in the minoxidil-treated group had moderate growth and 50% had minimal growth. This compared with 6% and 33%, respectively, in the placebo-treated group. Similarly, 60% of the patients in the 2% minoxidil group reported that they had new hair growth (20% moderate, 40% minimal) compared with 40% (7% moderate, 33% minimal) of the patients in the placebo group. No evaluations of dense hair growth were reported for either treatment group. No clinically significant changes in vital signs were observed and no serious or unexpected medical events were reported.\n Topical minoxidil was significantly more effective than placebo in the treatment of female androgenetic alopecia.", "Quantitative growth of hair over a 40-week period is reported for eight women with androgenetic alopecia. Using a random, double-blind protocol, the women were given either a 2% minoxidil solution or a placebo of vehicle only. Hair in a permanently marked site on the fronto-parietal scalp was pulled through a 1-cm-square clear plastic template, and the outline of the template was drawn on the scalp. The hair was carefully hand clipped and collected at five eight-week intervals (one untreated and four treated), using great care to collect only hairs within the marked area. Subsequent measurements included the total weight of hair grown in the marked area, the total number of hairs, and, on a randomized 50-hair subsample, the weight, lengths, and optical diameters. Calculated quantities included average weight per hair, average length, and average optical width. The average total hair weight of minoxidil-treated subjects increased over the 32-week test period by 42.5%, compared to 1.9% for the placebo-treated subjects (average p = 0.018). Changes for the average number count were 29.9% and -2.6%, respectively (average p = 0.022). These increases, observed using an unusually small number of subjects, clearly distinguished the treated subjects from the untreated. During the same test period, the averaged quantities of weight, diameter, and length from the 50-hair subsample showed insignificant change (p usually greater than 0.5). In addition to showing a larger percentage increase than did the total number, the total weight is not only easier to obtain, but less prone to error during sampling and measurement. Therefore, we recommend that total weight from a defined area be considered as the primary quantitative estimator for hair growth.", "The safety and efficacy of minoxidil 2% for the treatment of female androgenetic alopecia was assessed in a 32-week double-blind placebo-controlled trial. Thirty-three women aged 22 to 44 years with hair loss classified as Ludwig's grade I or II were enrolled, and 28 completed the trial. Before the administration of treatment, mean nonvellus hair counts were taken within a 1-cm2 target area of the scalp. For the 15 patients in the minoxidil group, the mean count was 169 hairs compared with 161 hairs for the 13 patients in the placebo group. At the completion of the trial, the patients treated with minoxidil 2% had a mean nonvellus hair count of 195 hairs versus a mean hair count of 177 for patients in the placebo group; 60% (9) of the patients in the minoxidil group showed minimal to moderate hair growth compared with 46% (6) of the patients in the placebo group. No serious side effects were encountered during this study, nor any significant changes in safety parameters. There were no dropouts due to medical events related to minoxidil 2%.", "Two drugs which are approved for the treatment of androgenetic alopecia in women in Germany were compared with regard to their influence on hair growth.\n Patients were randomized to group I (n = 52) who used 2% minoxidil solution twice daily for a period of 12 months or to group II (n = 51) who used 0.025% alfatradiol solution once daily for 6 months and were then switched to 2% minoxidil solution for months 7-12. Changes in hair growth parameters were determined using the TrichoScan.\n Topical treatment with 2% minoxidil solution for 6 months resulted in a significant increase of cumulative hair thickness (p < 0.0001) and absolute hair density (p < or = 0.0025), whereas these parameters of hair growth remained nearly unchanged after 6 months of treatment with alfatradiol solution. Evaluation of the same parameters from month 7 to month 12 demonstrated that 12 months minoxidil treatment resulted in an increasing stabilization (group I). After the alfatradiol-->minoxidil switch in group II a significant increase in cumulative hair thickness (p < 0.0001) and absolute hair density (p < 0.0001) was achieved. Both study medications were well tolerated.\n Treatment with minoxidil can induce an increase in hair density and hair thickness,whereas treatment with alfatradiol results in deceleration or stabilization of hair loss.", "Hormone studies have demonstrated the androgen-dependent character of female androgenetic alopecia, but there have been few controlled studies of therapies for alopecia in women.\n To compare topical minoxidil 2% and cyproterone acetate in the treatment of female alopecia.\n Sixty-six women with female-pattern alopecia were randomly assigned for 12 cycles into two groups, 33 received two local applications (2 mL day-1) of topical minoxidil 2% plus combined oral contraceptive and 33 received cyproterone acetate 52 mg day-1 plus ethinyl oestradiol 35 microg for 20 of every 28 days.\n A mean reduction of 2.4 +/- 6.2 per 0.36 cm2 in hairs of diameter > 40 microm was observed in the cyproterone acetate group (P = 0.05) and a mean increase of 6.5 +/- 9 per 0.36 cm2 in the minoxidil group (P < 0.001). Comparison of the total number of hairs at 12 months and the body mass index (BMI) revealed a borderline positive correlation in the cyproterone acetate group (r = 0.39, P = 0.06) and a negative correlation in the minoxidil group (r = -0.42, P < 0.05). No significant difference was observed in the total number of hairs among cyproterone acetate patients according to the presence or absence of other symptoms of hyperandrogenism, whereas in the minoxidil group, the total number of new hairs was higher in patients with isolated alopecia (Delta = 8.1; P < 0.05). Variations in scalp seborrhoea were significant in both groups, but the result was better (for acne and hirsutism as well) in the cyproterone acetate group than in the minoxidil group (P < 0.001).\n Minoxidil treatment was more effective in the absence of other signs of hyperandrogenism, hyperseborrhoea, and menstrual cycle modifications when the BMI was low, and when nothing argued in favour of biochemical hyperandrogenism. Cyproterone acetate treatment was more effective when other signs were present and when the BMI was elevated, factors that favoured a diagnosis of biochemical hyperandrogenism.", "Hair regrowth was evaluated by histologic analysis in men and women treated for androgenetic alopecia, by counting follicles in horizontal sections of scalp biopsies. Serial 4mm punch biopsies were taken at baseline and after 12mo of treatment from the transitional area of hair thinning between normal hair and vertex balding in men, and in an area of frontal/parietal thinning in women. Horizontal sections of reticular and papillary dermis were read by one observer, blinded to patient, treatment, and time. All terminal hair bulbs, terminal anagen and telogen hairs, and vellus and vellus-like miniaturized hairs were counted. Twenty-six men aged 18-41y, comprising 14 on finasteride 1 mg daily and 12 on placebo, and 94 postmenopausal women, aged 41-60y, comprising 44 on finasteride 1 mg daily and 50 on placebo, were evaluated. In the male study, the terminal hairs increased from a mean baseline count of 15.5-20.9 after 12mo of finasteride, versus 17.3-18.3 in the placebo patients. The miniaturized hairs decreased from 26.7 to 23.6 with finasteride versus 21.3-20.3 with placebo. The terminal-to-vellus ratio increased more in the finasteride than in the placebo patients, suggesting some reversal of the miniaturization process with finasteride. In the female study, no significant differences in follicular counts were found between the finasteride and placebo groups after 12mo of treatment. Follicular counts in horizontal sections provide an informative adjunct to noninvasive measures used in hair growth studies. Finasteride appears to be capable of reversing hair miniaturization in androgenetic alopecia in young to middle-aged men, but not in postmenopausal women.", "Finasteride, an inhibitor of type 2 5alpha-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated.\n The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA.\n In this 1-year, double-blind, placebo-controlled, randomized, multicenter trial, 137 postmenopausal women (41-60 years of age) with AGA received finasteride 1 mg/day or placebo. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, assessment of global photographs by a blinded expert panel, and histologic analysis of scalp biopsy specimens.\n After 1 year of therapy, there was no significant difference in the change in hair count between the finasteride and placebo groups. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. Similarly, patient, investigator, and photographic assessments as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning, increasing hair growth, or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. Finasteride was generally well tolerated.\n In postmenopausal women with AGA, finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning.", "Adenosine upregulates the expression of vascular endothelial growth factor and fibroblast growth factor-7 in cultured dermal papilla cells. It has been shown that, in Japanese men, adenosine improves androgenetic alopecia due to the thickening of thin hair due to hair follicle miniaturization. To investigate the efficacy and safety of adenosine treatment to improve hair loss in women, 30 Japanese women with female pattern hair loss were recruited for this double-blind, randomized, placebo-controlled study. Volunteers used either 0.75% adenosine lotion or a placebo lotion topically twice daily for 12 months. Efficacy was evaluated by dermatologists and by investigators and in phototrichograms. As a result, adenosine was significantly superior to the placebo according to assessments by dermatologists and investigators and by self-assessments. Adenosine significantly increased the anagen hair growth rate and the thick hair rate. No side-effects were encountered during the trial. Adenosine improved hair loss in Japanese women by stimulating hair growth and by thickening hair shafts. Adenosine is useful for treating female pattern hair loss in women as well as androgenetic alopecia in men.", "To pical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in men with androgenetic alopecia and women with female pattern hair loss. Results can be variable, and historic experience suggests that higher concentrations of topical minoxidil may enhance efficacy.\n The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare the efficacy and safety of 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of female pattern hair loss.\n A total of 381 women (18-49 years old) with female pattern hair loss applied 5% topical minoxidil solution (n = 153), 2% topical minoxidil solution (n = 154), or placebo (vehicle for 5% solution; n = 74) twice daily. Primary efficacy variables were change in nonvellus hair count at week 48, and patient and investigator assessments of change in hair growth/scalp coverage at week 48.\n After 48 weeks of therapy, 5% topical minoxidil was superior to placebo for each of the 3 primary efficacy measures. The 2% topical minoxidil group demonstrated superiority over placebo for hair count and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. The 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit at week 48. Both 5% and 2% topical minoxidil helped improve psychosocial perceptions of hair loss in women with female pattern hair loss. An increased occurrence of pruritus, local irritation, and hypertrichosis was observed with 5% topical minoxidil versus 2% topical minoxidil and placebo.\n In this 48-week study of 381 women with female pattern hair loss, 5% topical minoxidil was superior to placebo on each of the 3 primary efficacy end points: promoting hair growth as measured by change in nonvellus hair count and patient/investigator assessments of hair growth and scalp coverage. Application of 2% topical minoxidil was superior to placebo for assessments of nonvellus hair counts and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. At week 48, the 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit. Both concentrations of topical minoxidil were well tolerated by the women in this trial without evidence of systemic adverse effects. With the introduction of numerous herbal remedies for hair loss, of which most have not been tested in randomized, double-blind, placebo-controlled trials, it is important to describe well-controlled trials that demonstrate the efficacy and safety of topical drugs.", "Androgenetic alopecia is the most common cause of hair loss in men and women. Androgenetic alopecia in women begins as a diffuse and progressive thinning of the frontoparietal area of the scalp. In women, hair loss at any age is socially unacceptable and may be the basis of psychiatric illness.\n A 32-week, double-blind, placebo-controlled trial was conducted in 10 European centers to assess the efficacy and safety of 2% topical minoxidil solution for the treatment of androgenetic alopecia in women. Two hundred ninety-four of the 346 women enrolled (85%) completed the 32-week trial. Photographic and computer imaging techniques were used at each visit to determine objectively the number of nonvellus hairs present in a 1-cm2 area selected as the target evaluation site.\n In the 2% minoxidil group, the mean increase in nonvellus hair count was 33 hairs, which was significantly greater than that of 19 hairs in the placebo group (P = 0.0001). The investigators observed that 44% of the patients in the 2% minoxidil group achieved new hair growth compared with 29% in the placebo group. When asked to evaluate their own hair growth, 55% of the women in the 2% minoxidil group compared to 41% of the women in the placebo group believed that they had achieved new hair growth. No clinically significant changes in vital signs were observed during the study and no serious or unexpected medical events were reported.\n Topical minoxidil solution was significantly more effective than placebo in the treatment of androgenetic alopecia in women.", "Androgenetic alopecia (pattern baldness) affects approximately half of all white-skinned men and women over the age of 40 years. Based on preclinical studies in mice in which topical fulvestrant (ICI182,780, an anti-oestrogen) caused telogen hair follicles to enter anagen, thereby causing hair growth, a topical formulation of fulvestrant was developed for the potential treatment of androgenetic alopecia.\n To evaluate the efficacy of fulvestrant solution in stimulating hair growth in men and postmenopausal women with androgenetic alopecia in two randomized, phase II, minoxidil- and/or vehicle-controlled studies.\n One hundred and two white-skinned men aged 18-50 years with Norwood/Hamilton grades III, IIIv, IV, V or Va androgenetic alopecia received topical fulvestrant 70 mg mL(-1) solution, vehicle or minoxidil 2% solution twice daily for 16 weeks. Seventy postmenopausal women with Ludwig grade 1 or 2 androgenetic alopecia received topical fulvestrant 70 mg mL(-1) solution or vehicle twice daily for 16 weeks. The endpoints in both studies were hair density, cumulative hair thickness and hair growth rate, measured by TrichoScan analysis of digital images.\n There were no statistically significant differences favouring fulvestrant over vehicle at study end (day 113) for any of the efficacy parameters in men or women. Statistically significant differences in favour of minoxidil over fulvestrant were seen from day 57 onwards for hair density, cumulative hair thickness and hair growth rate in men.\n These results indicate a lack of effect of topical fulvestrant in the treatment of subjects with androgenetic alopecia. The reasons for this lack of effect remain unclear.", "nan", "Although twice-daily application of propylene glycol-containing 2% minoxidil topical solution (MTS) stimulates new hair growth, higher concentrations of minoxidil in a once-daily, propylene glycol-free formulation may improve efficacy and reduce unpleasant side effects.\n We sought to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia.\n A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The primary efficacy parameter was change from baseline in nonvellus target area hair count at week 24. Secondary end points included change in nonvellus target area hair width, overall efficacy by global photographic review as assessed by treatment-blinded evaluators and the subject herself, adverse events, and participants' assessment of product aesthetics.\n After 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with \"the treatment does not interfere with styling my hair\" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS.\n Because of differences in the formulations tested, study participants were not blinded to treatment.\n Once-daily 5% MTF is noninferior and as effective for stimulating hair growth as twice-daily 2% MTS in women with androgenetic alopecia and is associated with several aesthetic and practical advantages.\n Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.", "Minoxidil is effective in inducing hair growth in patients with androgenetic alopecia by stimulating hair follicles to undergo transition from early to late anagen phase. However, there have been no controlled studies of topical minoxidil in Asian women. The objective of this trial was to investigate the efficacy of 1% topical minoxidil for androgenetic alopecia in Japanese female patients using a double-blind controlled method. This trial included 280 Japanese female patients aged 20 years or older with androgenetic alopecia who were administered either 1% topical minoxidil (n = 140) or placebo (n = 140) for 24 weeks. The primary efficacy variable was mean change from baseline in non-vellus hair count/cm(2). The mean change was 8.15 in the 1% topical minoxidil group and 2.03 in the placebo group, with a significant difference between groups (p < 0.001) [difference: 6.12 (two-sided 95% confidence interval (CI): 3.29-8.96)]. Secondary variables included investigators' assessments and patients' self-assessments. As assessed by investigators, 29.2% (40/137) of the patients had moderate or better improvement in the 1% topical minoxidil group compared to 11.8% (16/136) in the placebo group (p < 0.001 versus placebo). The effect on hair growth was assessed as improved or better by 36.5% (50/137) of the patients themselves in the 1% topical minoxidil group compared to 23.5% (32/136) in the placebo group (p = 0.019 versus placebo). The patients tolerated treatment with 1% topical minoxidil well without significant adverse effects.", "In addition to the well-known hormonal influences of testosterone and dihydrotestosterone on the hair cycle, melatonin has been reported to have a beneficial effect on hair growth in animals. The effect of melatonin on hair growth in humans has not been investigated so far.\n To examine whether topically applied melatonin influences anagen and telogen hair rate in women with androgenetic or diffuse hair loss.\n A double-blind, randomized, placebo-controlled study was conducted in 40 women suffering from diffuse alopecia or androgenetic alopecia. A 0.1% melatonin or a placebo solution was applied on the scalp once daily for 6 months and trichograms were performed to assess anagen and telogen hair rate. To monitor effects of treatment on physiological melatonin levels, blood samples were taken over the whole study period.\n Melatonin led to a significantly increased anagen hair rate in occipital hair in women with androgenetic hair loss compared with placebo (n=12; P=0.012). For frontal hair, melatonin gave a significant increase in the group with diffuse alopecia (n=28; P=0.046). The occipital hair samples of patients with diffuse alopecia and the frontal hair counts of those with androgenetic alopecia also showed an increase of anagen hair, but differences were not significant. Plasma melatonin levels increased under treatment with melatonin, but did not exceed the physiological night peak.\n To the authors' knowledge, this pilot study is the first to show that topically applied melatonin might influence hair growth in humans in vivo. The mode of action is not known, but the effect might result from an induction of anagen phase.", "Female pattern alopecia is a common dermatologic condition that manifests after puberty. The only approved drug treatment for this condition is 2% minoxidil for topical application.\n This pilot study examined the effect of topical application of two niacin derivatives, octyl nicotinate and tetradecyl nicotinate, on hair fullness in female alopecia.\n Sixty female subjects with Ludwig types I-III female pattern hair loss were evaluated in a double-blinded, placebo-controlled (40 active, 20 placebo) design using standardized 35-mm photographic analyses for assessment of efficacy after 6 months of application.\n The niacin derivatives demonstrated a statistically significant increase in hair fullness (P = 0.04 compared to the placebo).\n Whereas evaluation of hair growth in women is challenging, this 6-month pilot study demonstrated statistically significant increase in hair fullness on blinded 35-mm photographic analysis. Long-term topical application of nicotinic acid derivatives offers promise for providing benefit in female alopecia and warrants further study.", "To determine the effectiveness of various antiandrogens for the treatment of premenopausal women with hyperandrogenic alopecia.\n Randomized, unmasked trial of three treatments in 36 hyperandrogenic women with alopecia and observation, without treatment, in 12 other similar patients.\n Endocrinologic outpatient practice in Italy.\n A total of 48 hyperandrogenic women with alopecia and 30 age- and weight-matched controls for the assessment of androgen levels.\n Randomization to cyproterone acetate (50 mg) with ethinyl estradiol (EE) in a reverse sequential regimen; flutamide (250 mg) or finasteride (5 mg) daily; all for 1 year. Twelve similar patients were observed without treatment for 1 year.\n Ludwig scores for hair thinning as well as patient and investigator assessments of treatment effectiveness.\n Flutamide resulted in a reduction of 21% in Ludwig scores (2.3 +/- 0.2 to 1.8 +/- 0.1). The other treatment effects were not statistically significant. Patient and investigator assessments showed a similar trend.\n Flutamide at a dose of 250 mg daily induced a modest improvement in alopecia after 1 year, whereas cyproterone acetate and finasteride were not effective. Treatment for more than 1 year may be required for better results." ]

[ "18765001", "16984757", "8752629", "16818032", "10527993", "9457941", "12009350", "15016780", "9389827", "19165663", "7836534", "12930575", "9647536", "11006179", "7851589" ]

[ "Progesterone supplementation during cryopreserved embryo transfer cycles: efficacy and convenience of two vaginal formulations.", "Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer.", "Glucocorticoid administration during transfer of frozen-thawed embryos: a prospective, randomized study.", "Delaying the initiation of progesterone supplementation until the day of fertilization does not compromise cycle outcome in patients receiving donated oocytes: a randomized study.", "A prospective randomized study comparing intramuscular with intravaginal natural progesterone in programmed thaw cycles.", "Experience with a novel vaginal progesterone preparation in a donor oocyte program.", "Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist.", "Pituitary suppression in ultrasound-monitored frozen embryo replacement cycles. A randomised study.", "Low-dose aspirin for oocyte donation recipients with a thin endometrium: prospective, randomized study.", "Low-dose human chorionic gonadotropin during the proliferative phase may adversely affect endometrial receptivity in oocyte recipients.", "The use of gonadotrophin-releasing hormone analogues in women receiving oocyte donation does not affect implantation rates.", "Luteinizing hormone affects uterine receptivity independently of ovarian function.", "The use of long- and short-acting forms of gonadotrophin-releasing hormone analogues in women undergoing oocyte donation.", "Prospective randomized trial to evaluate the efficacy of a vaginal ring releasing progesterone for IVF and oocyte donation.", "Low-dose glucocorticoids after in vitro fertilization and embryo transfer have no significant effect on pregnancy rate." ]

[ "Sequential exogenous oestradiol and progesterone are often used to prepare the endometrium in frozen embryo transfer (FET) cycles. This open-label, randomized study compared the efficacy and acceptability of self-administered once daily vaginal progesterone gel and vaginal micronized progesterone tablets (three times daily) for luteal support in FET cycles. An Asian population of women (aged < or = 45 years) were assigned randomly to receive progesterone gel (90 mg, once daily, n= 100) or vaginal micronized progesterone tablets (200 mg, three times daily, n= 100). All received oestradiol from day 2 of the menstrual cycle, for at least 10 days (or until endometrial thickness was > or =8 mm), before self-administering progesterone for 2 days before FET and up to 14 weeks afterwards if pregnancy occurred. Clinical pregnancy rates (31% for gel and 28% for tablets) and implantation rates (9.8% and 8.8%, respectively) were not significantly different between the treatment groups. Asian women using once daily progesterone gel found the gel easy to use and comfortable, and preferred it to their previous experience of vaginally administered tablets. In summary, once-daily vaginal progesterone gel has similar efficacy to vaginal tablets and is associated with high patient satisfaction.", "The objective of this study was to compare the implantation rate, pregnancy rate and endometrial thickness of frozen-thawed embryo transfers using endometrial preparation with either an artificial cycle or stimulated cycle. This was a prospective randomized trial at a single academic IVF centre. Seventy-seven patients undergoing artificial cycles received oral oestradiol; patients with endometrium < 7 mm on day 9-10 were switched to vaginal oestradiol. Eighty-six patients undergoing stimulated cycles received recombinant FSH followed by human gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior to embryo transfer. There was no difference in implantation rate (8.5% versus 7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or endometrium thickness (8.7 +/- 1.1 mm versus 8.7 +/- 1.0 mm) between artificial and stimulated cycles. Stimulated cycles had a higher incidence of thin endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to vaginal oestradiol had improved pregnancy rate (31%) versus patients who received oral oestradiol alone (13%) (P = 0.05). It is concluded that artificial and stimulated cycles produce comparable pregnancy rates, implantation rates, cancellation rates and endometrial thickness, although stimulated cycles have a higher incidence of thin endometrium. Vaginal oestradiol supplementation improved implantation rates.", "To establish whether there is any improvement in pregnancy and implantation rates after administration of \"low-dose,\" long-acting glucocorticoids during transfer of cryopreserved-thawed embryos.\n An IVF unit in a university hospital.\n Prospective, randomized study. Ninety-nine consecutive transfer cycles of frozen-thawed embryos to the uterine cavity of randomly chosen women diagnosed as having tubal factor infertility only. Fifty-two patients underwent transfer of frozen-thawed embryos and received 0.5 mg of dexamethasone; 47 women (control group) did not receive the drug during transfer.\n Normal ovulatory patients with tubal factor infertility.\n Oral dexamethasone administration before, during and after transfer of thawed embryos.\n Pregnancy and implantation rates.\n The pregnancy rate was 13.5% (7/52) in patients treated with the \"low-dose\" regimen of dexamethasone compared with 12.8% (6/47) in the control group. The implantation rate was similar.\n Our results demonstrated that the use of 0.5 mg dexamethasone for an immuno-suppressive effect, administered for a short period to patients diagnosed as having \"pure\" tubal factor infertility, did not improve the implantation or pregnancy rates.", "To determine whether the initiation of P supplementation as artificial luteal phase support (day -1, day 0, or day +1 of egg donation) in extensive programs of ovum donation influences cycle cancellation, pregnancy outcome, and implantation rate in day 3 embryo transfers.\n Prospective randomized trial.\n Oocyte donation program at the Instituto Valenciano de Infertilidad, Valencia, Spain.\n Three hundred recipients with normal ovarian function, absence of uterine anomalies, and undergoing their first egg donation were recruited between September 2003 and September 2004.\n A computer-based randomization divided the recipients into three groups when hCG was administered to their matched donors. The first group (group A) started P supplementation the day before oocyte retrieval; the second group (group B) started P supplementation on the day of the oocyte retrieval; and the third group (group C) started P supplementation 1 day after the egg retrieval once fertilization was confirmed.\n Implantation, pregnancy, and ongoing pregnancy rates were the primary outcome measures considered. The secondary outcome measure was the cancellation rate, especially due to fertilization failure.\n Global cancellation rate and cancellation rate due to fertilization failure were significantly higher in group A (12.4% and 8.2%, respectively) than in group C (3.3% and 0%, respectively). Reproductive outcome was similar in all the groups except for a higher biochemical pregnancy rate in group A (12.9%) than in groups B (6.6%) and C (2.3%).\n Initiation of P on day +1 of embryo development decreases cancellation rates of day 3 embryo transfers in extensive programs of ovum donation without any deleterious effect on pregnancy outcome or implantation rate.", "A simple programmed thaw cycle is described, during which the endometrium is prepared with oral oestradiol, followed by a natural progesterone source. This method involves minimal blood tests and uses inexpensive medications. Originally, an i.m. progesterone-in-oil preparation was used. Although highly successful in achieving high serum progesterone concentrations, the daily injections of the oily compound were found to be problematic from the patients' perspective. To examine the possibility of replacing the injectable progesterone with a vaginal preparation we conducted a prospective randomized study of 1 year's duration, during which time 170 and 184 thawing cycles were done with injectable and vaginal progesterone respectively. Although the progesterone blood concentrations obtained with the injectable preparation were more than twice those obtained with the vaginal progesterone, the clinical pregnancy rates (defined as percentage thawing cycles with gestational sac(s)/embryo transfer as demonstrated on ultrasound, 4 weeks after embryo transfer) were similar for both groups (15.9 and 16.8% respectively). Implantation and abortion rates were also comparable. These results agree with previous reports of higher uterine progesterone concentrations after the vaginal application. We conclude that the combination of oral oestradiol and vaginal progesterone is an effective, simple and inexpensive approach for programmed thaw cycles.", "To compare the efficacy of a vaginal progesterone preparation with our standard IM preparation within a donor egg program.\n Prospective randomized trial.\n Donor egg program at a university assisted reproductive therapy program (Jones Institute for Women's Health).\n Couples accepted into the donor egg program because of either premature ovarian failure or evidence of diminished ovarian reserve.\n Women were randomized into either a group receiving IM progesterone replacement or a group receiving vaginal progesterone replacement. Both groups underwent Estraderm patch/progesterone treatment in a mock cycle leading to an endometrial biopsy on day 26 followed by a second cycle in which ET was performed. Subjects with residual ovarian function received a GnRH agonist. In the IM treatment group, 100 mg was administered from cycle days 15 to 27. In the vaginal treatment group, Crinone 8%, a polycarbophil-based gel preparation containing 90 mg of micronized progesterone, was administered twice daily from the evening of day 14.\n Endometrial histology, serum levels of progesterone (on days 13, 17, 20, 24, and 26), the occurrence of pregnancy, implantation rate, and pregnancy outcome.\n Fifty-four women randomized into the vaginal progesterone treatment group and 18 women in the IM treatment group achieved ET. Mean serum progesterone levels were higher in the IM treatment group than in the Crinone group. Endometrial histology was \"in phase\" for all subjects in both groups. Clinical pregnancies were observed in 26 of 54 women and 5 of 18 women in the Crinone and IM progesterone groups, respectively. The ongoing pregnancy rate (PR) of 31% (17/54) and implantation rate of 23% in the subjects receiving Crinone was not statistically different from the IM progesterone group's ongoing PR of 22% (4/18) and implantation rate of 18%.\n Vaginal progesterone replacement with the polycarbophil gel preparation was as effective as IM progesterone in producing clinical and ongoing pregnancies within our donor egg program in the dosages administered.", "To test the efficacy of endometrial preparation with exogenous steroids, without pretreatment with gonadotropin-releasing hormone (GnRH) agonist, in women with normal ovarian function.\n Prospective randomized study.\n Private outpatient infertility clinic.\n Two hundred ninety-six women undergoing frozen-thawed embryo transfer.\n In group 1 (146 patients), depot GnRH agonist was administered in the luteal phase; treatment with 17beta-estradiol transdermal patches at steadily increasing dosage from 100 to 300 microg was then given for at least 12 days. In group 2 (150 patients), endometrial preparation began on day 1 of menstrual cycle. The starting dose was 200 microg; this was increased to 300 microg after 7 days.\n Pregnancy, abortion, implantation and cancellation rates.\n In group 2, six cycles (4%) were cancelled due to evidence of ovulation. Groups were similar in the percentage of embryos that survived freezing-thawing (77.1% in group 1 and 76.6% in group 2) and in the number of embryos transferred per patient (2.1 +/- 0.6 and 2.1 +/- 0.7, respectively). Groups 1 and 2 did not differ significantly in rates of pregnancy (19.7% and 24.1%), abortion (17.8% and 11.7%), and implantation (10.4% and 11.9%).\n Endometrial preparation for frozen-thawed embryo transfer based exclusively on steroid administration appears to be as effective as the more conventional protocol involving preliminary desensitization with a GnRH agonist. This simplified protocol reduces costs, minimizes pharmacologic treatment, and increases patient compliance.", "This study was designed to assess the value of using a gonadotrophin-releasing hormone (GnRH) agonist prior to exogenous steroid supplementation for endometrial preparation in frozen-thawed embryo replacement (FER) cycles.\n A prospective randomized trial of 234 patients undergoing FER cycles was conducted. The study population was randomly divided into two groups according to a computer-generated list. In group A (n = 117), a daily dose of 6 mg of oral estradiol valerate was initiated on menstrual day 1 following pituitary suppression using 400 mcg buserelin acetate daily. In group B (n = 117), the same dose of estradiol valerate was initiated on day 1 of bleeding without prior GnRH agonist therapy. In both groups, ovulation monitoring was not undertaken and progesterone pessaries (800 mg daily) were administrated when the endometrial thickness had reached 8 mm or more with embryo transfer taking place 2 days later.\n The two groups were comparable with respect to cause of infertility, age at stimulation (32.8 +/- 4 vs 33.2 +/- 3.9 years, P = 0.4), basal FSH level (6.3 +/- 1.7 vs 6.4 +/- 2 IU/l, P = 0.5), number of oocytes collected (16.9 +/- 7.3 vs 16.5 +/- 7.4, P = 0.7) and fertilized normally in the retrieval cycle (11.5 +/- 4.9 vs 11 +/- 4.9, P = 0.4) and number of embryos cryopreserved (6.6 +/- 3.6 vs 6.2 +/- 3.6, P = 0.3). There was no significant difference between the two groups in age at frozen replacement (33.6 +/- 4.2 vs 34 +/- 3.9 years, P = 0.4), duration of the proliferative phase (20.7 +/- 8.6 vs 21 +/- 9.2 days, P = 0.7) and number of thawed embryos replaced (2.3 +/- 0.6 vs 2.2 +/- 0.6, P = 0.2). However, compared with group B, group A achieved significantly higher pregnancy (37.6% vs 24%, OR 1.8, 95%CI 1.1-3.4), clinical pregnancy (24% vs 11.3%, OR 2.5, 95%CI 1.2-5.5) and live birth rates (20% vs 8.5%, OR 2.9, 95%CI 1.2-8).\n Medicated frozen embryo replacement cycles timed by endometrial thickness measurement alone without monitoring or suppression of ovarian activity are associated with reduced outcome.", "To evaluate the effect of low-dose aspirin use in oocyte donation recipients with an endometrial thickness of < 8 mm.\n A prospective, randomized study.\n An oocyte donation program in a private infertility practice.\n Twenty-eight recipients undergoing oocyte donation who failed to develop an endometrial thickness of at least 8 mm in a previous evaluation cycle.\n Fifteen recipients received low-dose aspirin (81 mg/d) in addition to standard hormone replacement for an oocyte donation cycle. The remaining 13 recipients did not receive aspirin.\n Clinical pregnancy rates, delivery rates, implantation rates, and change in endometrial thickness were compared in the aspirin and nonaspirin groups.\n There was no demonstrable increase in endometrial thickness in the aspirin-treated group. However, there was a statistically significant increase in implantation rates in the aspirin-treated group (24% versus 9%) and in implantation rates and clinical pregnancy rates in the aspirin-treated group when the final endometrial thickness was < 8 mm.\n Low-dose aspirin therapy improves implantation rates in oocyte donation recipients with a thin endometrium.", "The effect of low-dose human chorionic gonadotropin (hCG) administration in the proliferative phase of oocyte recipients was investigated in a prospective randomized trial. Sibling oocytes from the same donor were shared at random among two different recipients. In group I oocyte recipients received 750 IU of hCG every three days concomitant to endometrial preparation with estradiol until hCG injection to the donor, whereas in group II recipients received no hCG during endometrial priming with estradiol. Endometrial thickness was significantly lower in group I compared with group II, although similar endometrial thickness was detected during the mock cycle. Pregnancy rates were significantly lower in group I than in group II (13.6% vs. 45.4%, p<0.05). Implantation rates were also significantly lower in group I (1.7% vs. 22.4%, p<0.01). The study was discontinued prematurely for ethical reasons when 22 cycles were completed, as pregnancy rates were very low in group I. In conclusion, hCG administration in the proliferative phase might directly affect endometrial proliferation and receptivity.", "There is conflicting clinical evidence suggesting a positive role for gonadotrophin-releasing hormone analogues (GnRHa) on implantation in humans. This potential effect was evaluated in this study taking the oocyte donation programme as a model. Patients were randomly allocated into one of the two treatment groups: group I received simultaneous treatment with GnRHa and steroids, and group II only received exogenous steroid replacement. An analysis of the donors and semen quality showed similarity between recipient groups. There was no significant difference between groups in the number and quality of embryos replaced, clinical pregnancy and implantation rates. In summary, using a model in which the endometrium can be analysed independently of the embryos, the results suggest that GnRHa are neither effective nor detrimental for embryo implantation in humans.", "Previous studies have suggested that LH, in addition to its well-known effects on the ovary, may exert direct effects on the uterus. This study evaluated the effects of mid-cycle administration of human chorionic gonadotrophin (HCG), which signals through the LH receptor, on endometrial thickness and uterine receptivity in two groups of women lacking ovarian activity and receiving embryos from an oocyte donation programme. Patients in one group still had ovulatory cycles, but their ovarian function was suppressed by pituitary down-regulation with a gonadotrophin-releasing hormone (GnRH) agonist in the embryo transfer cycle, resulting in low endogenous LH concentrations. Patients in the other group were menopausal women whose pituitary function was not down-regulated in the embryo transfer cycle and whose endogenous LH concentrations were thus high. Patients in each of the two groups were randomized into two subgroups. Patients in one subgroup were given 5000 IU of HCG 2 days before oocyte recovery in the corresponding donor. Patients in the other subgroup received placebo at the same time. Oocytes from each donor were randomly distributed between one patient from the HCG subgroup and one patient from the placebo subgroup in each patient group. Endometrial growth and secretory transformation were stimulated by sequential treatment with oestradiol valerate and progesterone. In women with low endogenous LH receiving placebo, endometrial thickness stopped increasing at the beginning of secretory transformation. Mid-cycle HCG administration resulted in a continuous increase in endometrial thickness through this period, improved the implantation rate after embryo transfer in these women (30.6 versus 20.7%) and augmented the number of multiple pregnancies. No similar stagnation of endometrial thickness and no effects of mid-cycle HCG administration on endometrial thickness, the implantation rate and the number of multiple pregnancies were found in women with high endogenous LH. It is concluded that endometrial maturation is disturbed in women with low endogenous LH but can be rescued by mid-cycle stimulation of LH receptor with exogenous HCG in the absence of ovarian activity.", "Evidence accumulated in in-vitro fertilization (IVF) cycles suggests that the use of long-acting forms of gonadotrophin-releasing hormone analogues (GnRHa) for pituitary desensitization may impair the outcome of IVF as compared to classical short-acting formulations. Whether the negative effects are directed against the corpus luteum, the endometrium, or both is unknown. However, the presence of high affinity binding sites for gonadotrophin-releasing hormone (GnRH) in the human endometrium suggests a possible role of these analogues on this target organ, affecting embryo implantation. In the present study, we tested direct effects of two different forms of GnRHa on implantation using the ovum donation model. Patients were prospectively allocated to one of the three study groups: the short-acting form of the analogue leuprolide acetate (group I; n=64), the long-acting form of the same analogue (group II; n=58), and the long-acting preparation of the analogue tryptorelin (group III; n=61). A total of 68 cycles of embryo transfer was carried out in group I, whereas 67 were performed in group II and 65 in group III. Cancellation rates were respectively 18.1, 17.3 and 18.8% because of bleeding while being on the waiting list for anonymous oocyte donation. The number of oocytes donated, fertilization rates and embryos replaced in each group were similar. As a result, pregnancy rate per transfer was 38.2, 49.3 and 44.6% respectively. Implantation rates per embryo replaced were respectively 13.4, 19.1 and 17.0%. These data suggest that the use of a long-acting form of GnRHa provides success rates similar to the short-acting preparations, resulting in more convenient medication for patients with ovarian function included in ovum donation programmes.", "A polysyloxane vaginal ring containing 1g of natural progesterone was developed as luteal supplementation for women treated with IVF-embryo transfer and for agonadal women participating in an oocyte donation programme. The ring provides continuous release of progesterone (10-20 nmol/l) for 90 days. The efficacy of this form of progesterone supplementation was evaluated in two multicentre prospective randomized trials. IVF-embryo transfer trial: After oocyte aspiration, 505 women were randomly allocated to progesterone supplementation with vaginal ring or i.m. progesterone (50 mg/day). The clinical pregnancy rate was 36.6% in both groups. Implantation rate was 15.9% in the vaginal ring and 16.0% in i.m. progesterone. Oocyte donation trial: After endometrial proliferation with micronized oestradiol, 153 women were allocated to progesterone replacement with a vaginal ring or i.m. progesterone (100 mg/day). Clinical pregnancy rate was 39.8 and 28.6% respectively. Implantation rate was significantly higher with the vaginal ring compared with i.m. progesterone (19.9 and 11.6% respectively, P = 0.006). The vaginal ring is a novel development which provides continuous release of progesterone for 90 days. In IVF-embryo transfer, its effectiveness is similar to daily i.m. injections. In oocyte donation the ring provides a progestative milieu which improves the implantation rate and eliminates the discomfort of daily i.m. injections.", "To determine the effect on pregnancy rate (PR) of low-dose glucocorticoid treatment in cycles without micromanipulation.\n Randomized, prospective, double-blinded, placebo-controlled trial.\n One university-based tertiary infertility center and two private infertility centers.\n All patients receiving standard stimulation IVF-ET or transfer of cryopreserved embryos at the participating facilities from January to September 1993 were asked to participate in this study. Patients having micromanipulation were excluded from this study.\n Participating patients were randomized to either 16 mg oral 6-alpha-methylprednisolone for four evenings starting the evening of retrieval or the evening before thawing cryopreserved embryos or to placebo administered in an identical fashion. Both groups were treated with 250 mg oral tetracycline four times per day starting with initiation of the study medication and continuing for 4 days. Cryopreservation and stimulation cycles were managed according to pre-established protocols for all patients. A clinical pregnancy was confirmed by an appropriately rising hCG titer and a gestational sac on ultrasound.\n A total of 206 stimulation patients and 61 cryopreservation patients were randomized and had an ET. Patient characteristics were similar between groups. The clinical pregnancy and implantation rates between placebo and glucocorticoid groups were 35.9% versus 40.8% and 12.8% versus 11.7% for stimulation cycles and 30.3% versus 25% and 9.9% versus 7.4% for cryopreservation cycles, respectively. None of these differences were statistically significant.\n Glucocorticoid plus antibiotic treatment at these doses for transfers of nonmicromanipulated embryos does not appear to have a significant effect on pregnancy or implantation rates." ]

[ "8201068", "15944167" ]

[ "The treatment of recurrent abdominal pain in children: a controlled comparison of cognitive-behavioral family intervention and standard pediatric care.", "A randomized controlled trial of a cognitive-behavioral family intervention for pediatric recurrent abdominal pain." ]

[ "This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment.", "To investigate whether the combination of standard medical care (SMC) and short-term cognitive-behavioral family treatment (CBT) in the treatment of recurrent abdominal pain (RAP) was more effective than SMC alone.\n Children recently diagnosed with RAP via physician examination were randomized into SMC (n = 29) and SMC plus CBT (n = 40) groups. Outcome measures included multiple dimensions of child and parent reported child pain, somatization, and functional disability, and school absences and physician contacts.\n Children and parents participating in the combined SMC + CBT intervention reported significantly less child and parent reported child abdominal pain than children in the SMC intervention immediately following the intervention and up to 1 year following study entry, as well as significantly fewer school absences. Significant differences in functional disability and somatization were not revealed.\n These results, in combination with previous studies, add support to the effectiveness of CBT intervention in reducing the sensory aspects of RAP. Results are discussed with respect to the cost-benefit of integrated medical and short-term psychological services." ]

[ "10765510", "19250367", "16880306" ]

[ "Randomized trial of administration of prostaglandin E2 gel for induction of labor in the morning or the evening.", "Start of induction of labour with oxytocin in the morning or in the evening. A randomised controlled trial.", "Morning compared with evening induction of labor: a nested randomized controlled trial. A nested randomized controlled trial." ]

[ "To compare the outcome of induction of labor and patient's preferences using a protocol with the first dose of prostaglandin E2 endocervical gel in the evening versus a protocol with the first dose in the morning.\n We performed a randomized trial comparing administration of prostaglandin E2 endocervical gel in the morning with administration of prostaglandin E2 gel in the evening, followed if necessary by a second dose being given after six hours if labor had not started or the cervix was still unripe. Formal induction of labor by amniotomy and oxytocin infusion was performed the morning after the initial prostaglandin E2 dose. Patients' preferences were assessed using a questionnaire that was completed after delivery.\n Tertiary care hospital in the Netherlands with 1,600 deliveries per year.\n One-hundred and twenty-six women with viable singleton pregnancies at term who had induction of labor with prostaglandins.\n Time of delivery (daytime, evening or night) and patient's satisfaction.\n Fifty-eight women were allocated for administration of gel in the morning, whereas 68 had their gel in the evening. Administration of gel in the evening did not significantly reduce delivery between 23.00 hours and 08.00 hours, although there was a reduction in delivery between 23.00 hours and 08.00 hours in nulliparae. None of the multiparous women delivered between 18.00 hours and 23.00 hours after induction of labor in the evening. The relative risk for delivery by vacuum or forceps was increased after allocation of gel in the evening (4.2; 95% confidence limits 1.4 to 13). Patients' preferences favored administration of gel in the morning.\n There was no benefit in starting induction of labor with prostaglandin E2 in the evening, compared with starting in the morning.", "The objective of this study was to compare outcomes of induced labour with intravenous oxytocin with a start in the evening versus in the morning.\n Randomised controlled trial.\n Labour wards of three hospitals in Amsterdam, the Netherlands.\n Women with an indication for induction of labour with intravenous oxytocin.\n Included women were randomized to either the evening group with a start of induction of labour at 21:00 hours, or the morning group with a start at 07:00 hours.\n Primary outcome was duration of labour. Secondary outcomes were instrumental delivery rate, adverse neonatal outcome defined as an Apgar score below 7 after 5 minutes, number and indications of paediatric consults and neonatal admissions, duration of second stage, number of intrapartum infections and necessity of pain relief.\n We randomised 371 women. Mean duration of labour was not significantly different (primiparae: morning 12 hours and 8 minutes versus evening 11 hours and 22 minutes, P value 0.29; multiparae: morning 7 hours and 34 minutes versus evening 7 hours and 46 minutes, P value 0.70). There were no significant differences in instrumental deliveries rates, number of infections or patient satisfaction. Unexpectedly, neonatal outcome was better in women induced in the evening.\n Induction of labour with intravenous oxytocin in the evening is equally effective as induction in the morning.", "To test the hypothesis that commencing induction of labor in the morning more closely reflects the physiologic timing of onset of labor and is associated with fewer women who remain undelivered 24 hours after cervical ripening and induction begins.\n This was a nested randomized clinical trial, conducted between April 2001 and December 2004. Pregnant women at more than 36+6 weeks gestation with a cephalic presentation who were scheduled for prostaglandin induction of labor were eligible to participate. Women were randomly assigned to either admission in the morning (0800 hours) or admission in the evening (2,000 hours). The primary outcome measures were vaginal birth not achieved in 24 hours, uterine hyperstimulation with associated fetal heart rate changes, and cesarean delivery.\n A total of 620 women were entered in the trial, with 280 women in the morning admission group and 340 women in the evening admission group. There were no statistically significant differences between the timing of admission for induction and the primary trial outcomes. However, women admitted in the morning were less likely to require oxytocin infusion (morning admission 126 of 280 [45.0%] compared with evening admission 184 of 340 [54.1%]; relative risk 0.83, 95% confidence interval 0.70-0.97; P=.022). Nulliparous women admitted in the morning were less likely to require operative vaginal birth (morning admission 10 of 62 [16.1%] compared with evening admission 28 of 82 [34.2%]; relative risk 0.47, 95% confidence interval 0.25-0.90; P=.015).\n For women who require induction of labor, consideration should be given to admission in the morning rather than admission in the evening.\n Australian Clinical Trials Registry, www.actr.org.au, 12606000156583." ]

[ "10023500", "10907738", "7726322", "11254020" ]

[ "Combination of inositol and serotonin reuptake inhibitors in the treatment of depression.", "Inositol addition does not improve depression in SSRI treatment failures.", "Double-blind, controlled trial of inositol treatment of depression.", "Inositol as an add-on treatment for bipolar depression." ]

[ "Inositol has been reported to be an effective treatment in depression, and we hypothesized that inositol addition might enhance or speed up response to serotonin selective reuptake inhibitors (SSRI).\n Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol. Hamilton Depression Rating Scale was used as an assessment tool at baseline, and 1, 2, 3, and 4 weeks.\n No significant difference was found between the two treatment groups.\n Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [e.g., monoamine oxidase inhibitors (MAOI) plus tricyclic antidepressants (TCA), TCA plus lithium]. By contrast, augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol.", "Some antidepressants, such as Lithium, can augment the antidepressant effect of serotonin selective uptake inhibitors (SSRI) in patients who have failed to respond to SSRI. Inositol has demonstrated antidepressant effects but in a controlled double blind augmentation trial did not improve depression in SSRI treatment failures.", "CSF levels of inositol have been reported to be lower than normal in depressed subjects. The authors administered inositol to depressed patients in a double-blind, controlled trial.\n Under double-blind conditions, 12 g/day of inositol (N = 13) or placebo (N = 15) was administered to depressed patients for 4 weeks.\n The overall improvement in scores on the Hamilton Depression Rating Scale was significantly greater for inositol than for placebo at week 4. No changes were noted in hematology or in kidney or liver function.\n This may be the first use of the precursor strategy for a second messenger rather than a neurotransmitter in treating depression. Although inositol had a significant antidepressant effect in this study, replication is crucial.", "Inositol is a constituent of the intracellular phosphatidyl inositol (PI) second messenger system, which is linked to various neurotransmitter receptors. Inositol crosses the blood-brain barrier in pharmacological doses, and has shown efficacy in a small double-blind study of unipolar depression. This pilot study evaluated its potential efficacy and safety in bipolar depression.\n Twenty-four consenting adult men and women with DSM-IV bipolar depression (bipolar I = 21; bipolar II = 3) were randomly assigned to receive either 12 g of inositol or D-glucose as placebo for 6 weeks. Efficacy and safety ratings were done weekly. Thymoleptic medications (lithium, valproate, carbamazepine) in stable doses and at therapeutic levels at study entry were continued unchanged.\n Two subjects receiving placebo dropped out early due to worsening or non-adherence to the protocol. Among the 22 subjects who completed the trial, six (50%) of the inositol-treated subjects responded with a 50% or greater decrease in the baseline Hamilton Depression Rating Scale (HAM-D) score and a Clinical Global Improvement (CGI) scale score change of 'much' or 'very much' improved, as compared to three (30%) subjects assigned to placebo, a statistically nonsignificant difference. On the Montgomery-Asberg Depression Rating Scale (MADRS), eight (67%) of twelve inositol-treated subjects had a 50% or greater decrease in the baseline MADRS scores compared to four (33%) of twelve subjects assigned to placebo (p = 0.10). Inositol was well tolerated with minimal side effects, and thymoleptic blood levels were unaltered.\n These pilot data suggest a controlled study with an adequate sample size, and the appropriate rating scale may demonstrate efficacy for inositol in bipolar depression. The tolerability and the 'natural substance' aspect of inositol may be particularly appealing to subjects with bipolar depression." ]

[ "15193678", "11511121", "16537663", "16537725" ]

[ "A dose-finding study of fondaparinux in patients with non-ST-segment elevation acute coronary syndromes: the Pentasaccharide in Unstable Angina (PENTUA) Study.", "A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study.", "Comparison of fondaparinux and enoxaparin in acute coronary syndromes.", "Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial." ]

[ "In this dose-finding study, we sought to compare fondaparinux with enoxaparin in patients with acute coronary syndromes (ACS).\n Fondaparinux is a synthetic pentasaccharide that selectively inhibits activated clotting factor X. It has been demonstrated as effective in preventing thromboembolic complications in orthopedic surgery.\n Four doses fondaparinux (2.5, 4, 8, or 12 mg once daily) and enoxaparin (1 mg/kg twice daily) were compared, both given for three to seven days, in patients with ACS without persistent ST-segment elevation.\n The rates of the combined primary end point of death, myocardial infarction, or recurrent ischemia after nine days were 27.9%, 35.9%, 34.7%, 30.3%, and 35.7% in patients allocated to fondaparinux doses of 2.5, 4, 8, and 12 mg and enoxaparin, respectively (p = NS). In the per-protocol analysis (929 patients who received adequate study drug and had adequate ST-segment monitoring), these figures were 30.0%, 43.5%, 41.0%, 34.8%, and 40.2%. Again, no dose response was observed. The lowest event rates were observed in the 2.5-mg fondaparinux group, which had significantly lower rates than the enoxaparin group as well as for 4 and 8 mg fondaparinux in the per-protocol analysis (p < 0.05). Bleeding rates were low and not different among the patient groups. No differences were observed in fondaparinux concentrations in patients with or without death, myocardial infarction, recurrent ischemia, or bleeding events.\n This dose-finding study revealed no dose response for different fondaparinux doses ranging from 2.5 to 12 mg subcutaneously and suggests that the efficacy and safety of fondaparinux may be similar to that of enoxaparin. Further studies with fondaparinux in ACS might include the lowest dose (2.5 mg) investigated in this study.", "ORG31540/SR90107A, a synthetic pentasaccharide, is a selective inhibitor of factor-Xa. It was hypothesized that prolonged factor-Xa inhibition with pentasaccharide may be an effective and safe antithrombotic co-therapy in acute myocardial infarction.\n Patients (n=333) with evolving ST-segment elevation acute myocardial infarction were treated with aspirin and alteplase and randomized to unfractionated heparin, given intravenously during 48 to 72 h, or to a low, medium or high dose of pentasaccharide, administered daily for 5 to 7 days, intravenously on the first day, then subcutaneously. Coronary angiography was performed at 90 min and on days 5 to 7. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 rates at 90 min were similar in the four treatment groups. Among patients with TIMI 3 flow at 90 min and who did not undergo a coronary intervention (n=155), a trend towards less reocclusion of the infarct-related vessel on days 5 to 7 was observed with pentasaccharide: 0.9% vs 7.0% with unfractionated heparin (P=0.065). Also, fewer revascularizations during the 30-day follow-up period were performed in patients given pentasaccharide (39% vs 51% for unfractionated heparin;P=0.054). The primary safety end-point, the combined incidence of intracranial haemorrhage and need for blood transfusion, was identical with pentasaccharide and unfractionated heparin (7.1%). One non-fatal intracranial haemorrhage occurred in the 241 patients given pentasaccharide (0.4%).\n In this study, pentasaccharide given together with alteplase was safe and as effective as unfractionated heparin in restoring coronary artery patency. Prolonged administration of pentasaccharide was associated with a trend towards less reocclusion and fewer revascularizations. Selective factor-Xa-inhibition seems to be an attractive therapeutic concept in patients presenting with ST-segment elevation acute myocardial infarction.\n Copyright 2001 The European Society of Cardiology.", "The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding.\n We randomly assigned 20,078 patients with acute coronary syndromes to receive either fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months.\n The number of patients with primary-outcome events was similar in the two groups (579 with fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P<0.001). The composite of the primary outcome and major bleeding at nine days favored fondaparinux (737 events [7.3 percent] vs. 905 events [9.0 percent]; hazard ratio, 0.81; P<0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days (295 vs. 352, P=0.02) and at 180 days (574 vs. 638, P=0.05).\n Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity. (ClinicalTrials.gov number, NCT00139815.).\n Copyright 2006 Massachusetts Medical Society.", "Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy.\n To evaluate the effect of fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI.\n Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12,092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment.\n Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months).\n Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with fondaparinux at 9 days.\n In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes.\n ClinicalTrials.gov Identifier NCT00064428." ]

[ "8103365", "1773316", "8156369", "11005498", "8044618", "9864116", "1338091", "1734574", "9231856", "16575620", "15449272" ]

[ "Clinical and functional results of abdominal rectopexy with absorbable mesh-graft for treatment of complete rectal prolapse.", "Lateral ligament division during rectopexy causes constipation but prevents recurrence: results of a prospective randomized study.", "Abdominal resection rectopexy with pelvic floor repair versus perineal rectosigmoidectomy and pelvic floor repair for full-thickness rectal prolapse.", "Effects of rectal mobilization and lateral ligaments division on colonic and anorectal function.", "Prospective randomized trial of Ivalon sponge versus sutured rectopexy for full-thickness rectal prolapse.", "Comparison of laparoscopic rectopexy with open technique in the treatment of complete rectal prolapse: clinical and functional results.", "Abdominal rectopexy with sigmoidectomy vs. rectopexy alone for rectal prolapse: a prospective, randomized study.", "A prospective randomized study of abdominal rectopexy with and without sigmoidectomy in rectal prolapse.", "Comparison of polyglycolic acid and polypropylene mesh for rectopexy in the treatment of rectal prolapse.", "Impact of new technologies on the clinical and functional outcome of Altemeier's procedure: a randomized, controlled trial.", "Economic impact of laparoscopic versus open abdominal rectopexy." ]

[ "To report the long term results of abdominal rectopexy in patients with complete rectal prolapse.\n Ongoing prospective randomised study.\n Department of Surgery, Westfälische Wilhelms-University, Münster.\n 47 patients with complete rectal prolapse operated on between 1982 and 1989.\n Abdominal rectopexy with absorbable mesh made of either polyglycolic acid (n = 17) or polyglactine 910 (n = 30).\n Postoperative complications and late results at a mean of 50.5 (range 2-102) months after operation.\n Thirteen patients (28%) developed postoperative complications, most of them minor; there was one enterocutaneous fistula. Thirty five patients (74%) were available for late follow up. There were no case of recurrent prolapse and 5 (14%) had developed mucosal prolapse. Of the 22 patients who had been incontinent before operation, 8 had become totally continent and 6 partially continent Overall continence improved in 18 (51%) of the 35 patients. Three patients who were continent before operation had become incontinent.\n Absorbable mesh is a suitable material for abdominal rectopexy.", "Denervation of the rectum during rectopexy has been suggested as a reason for postoperative constipation. Bowel symptoms and anorectal function have been examined in a prospective randomized study of rectopexy with (n = 14) or without (n = 12) division of the lateral ligaments. Incontinence improved in both groups of patients. Division of the lateral ligaments increased the number of patients with constipation (three before operation, ten after operation, P less than 0.01). Mean and canal pressures were higher after operation in all patients. Rectal electrical sensory threshold increased significantly in those in whom the ligaments had been divided (preoperative 27.6 mA versus postoperative 56.7 mA; P less than 0.01) but not in those in whom they were preserved (39.0 versus 34.9 mA; P greater than 0.05). Prolapse recurred in six patients who did not undergo division of the lateral ligaments, but in none of the group in whom the ligaments were divided.", "A randomized trial was performed to compare abdominal resection rectopexy and pelvic floor repair (n = 10) with perineal rectosigmoidectomy and pelvic floor repair (n = 10) in elderly female patients with full-thickness rectal prolapse and faecal incontinence. There were no recurrences of full-thickness prolapse following resection rectopexy but one after rectosigmoidectomy. Continence to liquid and solid stool was achieved in nine patients, with faecal soiling reported in only two, after resection rectopexy and in eight, with soiling in six, following rectosigmoidectomy. The median (range) frequency of defaecation was only 1 (1-3) per day following resection rectopexy compared with 3 (1-6) per day after rectosigmoidectomy. There was an increase in the mean(s.d.) maximum resting pressure after resection rectopexy (19.3(15.28) cmH2O) compared with a reduction following rectosigmoidectomy (-3.4(13.75) cmH2O) (P = 0.003). Mean(s.d.) compliance was also greater after resection rectopexy than following rectosigmoidectomy (3.9(0.75) versus 2.2(0.78) ml/cmH2O, P < 0.001). Abdominal resection rectopexy gives better functional and physiological results than perineal rectosigmoidectomy.", "Colonic and anorectal function are altered after posterior rectopexy. The aim of this randomized, prospective study was to evaluate the effects of rectal mobilization and division of the lateral ligaments on colonic and anorectal function.\n Posterior rectopexy was performed in 18 patients with complete rectal prolapse. Anal manometry and measurement of rectal compliance, total and segmental colonic transit time, constipation score, and defecation frequency were performed preoperatively and three months postoperatively. Ligaments were divided in ten patients.\n Mean preoperative total transit time was similar between the two patient groups and doubled postoperatively (P = 0.03). Mean postoperative segmental transit time increased by a factor of 1.7 in segments I (ascending colon) and II (descending colon) and by a factor of 2.3 in segment III (rectosigmoid). The same pattern was found in both groups. Mean resting pressure decreased after division of the lateral ligaments and increased after preservation. Mean rectal compliance decreased after division of the ligaments and increased when they were preserved. Mean postoperative constipation score differed little from the preoperative score. Mean defecation frequency was decreased in the group with the ligaments preserved and increased in the group with the ligaments divided. None of the effects of rectal mobilization or division of the lateral ligaments on anorectal function reached statistical significance.\n Rectal mobilization had a statistically significant effect on colonic function. Total and segmental colonic transit times doubled. The effects on anorectal function were not significant. Division of the lateral ligaments did not significantly influence postoperative functional outcome.", "Ivalon sponge rectopexy is a safe reliable procedure in the management of rectal prolapse. Sutured rectopexy is simpler and avoids the use of foreign material. Sutured rectopexy is mandatory if synchronous resection is to be considered. Sixty-three patients (62 women) with full-thickness rectal prolapse were entered into a prospective randomized trial of Ivalon sponge rectopexy (31 patients) versus sutured rectopexy (32). Twenty patients (32 per cent) had coexistent incontinence (ten in each group). The operation was performed in the standard manner with a sutured rectangle of sponge or sutures alone placed along the length of the sacrum. Postoperative morbidity occurred in nine patients (14 per cent) of whom three underwent a sutured procedure and six Ivalon rectopexy: wound infection in three, chest infection in two, urinary tract infection in two and thromboembolism in two. There were no deaths within 30 days. At a median follow-up of 47 months prolapse had recurred in two patients (3 per cent), one in each group, 14 (22 per cent) suffered from incontinence (of whom five had undergone a sutured procedure), while 25 (40 per cent) had developed constipation (of whom 15 had received Ivalon rectopexy). The medium-term results of rectopexy by suture alone are equivalent to those obtained following the conventional Ivalon procedure. These data suggest that Ivalon rectopexy could now be abandoned.", "The aim of this retrospective study was to compare the functional and clinical results of laparoscopic rectopexy with those of the open technique in two similar groups of patients with complete rectal prolapse and fecal incontinence. Between November 1992 and June 1997, 21 patients underwent abdominal rectopexy. Thirteen patients (group A: 12 women and 1 man, mean age 52.9 years, range 28-70) and 8 patients (group B: 8 women, mean age 58.2 years, range 20-76) were submitted to Well's rectopexy by the open technique and the laparoscopic approach, respectively, without division of the lateral rectal ligaments. Assignment to each group was done randomly. Before the operation, a detailed clinical history was taken, and patients were studied with inspection and digital examination of the anorectum, proctosigmoidoscopy, determination of pancolonic transit time, dynamic defecography, anorectal manometry, and anal electromyography. After the operation, all patients underwent perineal physiotherapy, external electric stimulation, and perineal biofeedback. The mean follow-up time was 29.5 months (range 6-54) in group A and 25.7 months (range 8-45) in group B. Values were compared by chi-square, Mann-Whitney U, and Wilcoxon tests, as appropriate; differences were considered significant at p < 0.05. In both groups, dyschezia and fecal incontinence improved significantly (p < 0.05) after the operation. Basal pressure of anal sphincter, squeezing pressure, and rectoanal reflex improved without significance, whereas anoperineal pain was not significantly reduced. In group B, the postoperative hospital stay was shorter than in group A, with a marked reduction of costs. Laparoscopic Well's rectopexy has the same clinical and functional results as the open technique, with a shorter postoperative hospital stay and lower costs.", "A prospective, randomized study comparing abdominal rectopexy and sigmoid resection (Group I; n = 15) with polyglycolic acid mesh rectopexy without sigmoidectomy (Group II; n = 15) for complete rectal prolapse was carried out. One patient in Group I died of myocardial infarction, one patient in Group II had a small bowel obstruction and two patients in Group I an asymptomatic stricture of the anastomosis. Otherwise a safe and efficient control of the prolapse was achieved in both groups. Eleven (73%) patients in Group I and 12 (80%) patients in Group II were more or less incontinent before surgery. After correction of prolapse incontinence improved in eight and ten patients in Groups I and II, but became slightly worse in one patient in Group II. A similar rise in anal pressures was measured in both groups after surgery. Constipation disappeared in three and seven patients in Groups I and II six months after surgery, but five additional patients in Group II became severely constipated and colectomy had to be performed in one of them. Surgery caused no significant change in colonic transit times even though increased transit times were measured in each group six months postoperatively. Sigmoid resection in conjunction with rectopexy does not seem to increase operative morbidity but tends to diminish postoperative constipation possibly by causing less outlet obstruction.", "Eighteen patients with full-thickness prolapse of the rectum were randomized to rectopexy alone (group 1) or with sigmoidectomy (group 2). Three months postoperatively, seven patients in group 1 and two in group 2 complained of severe constipation. One patient in group 1 and three patients in group 2 remained incontinent. The results of colonic marker studies showed a significant increase in the number of markers at day 5 for those in group 1 (preoperative, 7.7 +/- 2.6; postoperative, 14.6 +/- 2.2; t test, p less than 00.1) but no significant increase in group 2 (preoperative, 4.6 +/- 2.2; postoperative 6.8 +/- 2.3; t test, p less than 0.01). No significant changes or differences between the groups were seen in the anorectal angle on videoproctogram. The results of anorectal physiologic studies done postoperatively showed no differences between the groups in maximum resting pressure, sphincter length or saline solution infusion test; however, the patients in group 1 had a significantly greater rectal compliance (group 1, 0.24 +/- 0.02 millimeters mercury per milliliter; group 2, 0.1 +/- 0.02 millimeters mercury per milliliter; p less than 00.1). This may occur because the redundant loop of sigmoid colon causes hold-up of intestinal content and kinking at the junction between the sigmoid colon and the rectum.", "To compare the efficacy of absorbable and non-absorbable mesh for rectal fixation in abdominal rectopexy.\n Prospective open study.\n University hospital, Israel.\n 37 consecutive patients with complete rectal prolapse.\n Posterior abdominal rectopexy with non-absorbable mesh (Polypropylene, Prolene, Ethicon Ltd) in 17 patients and with absorbable mesh (Polyglycolic acid, Dexon, Davis & Geck) in 20.\n There was no operative mortality, and there were no significant differences between the groups in the incidence of postoperative complications. Mean (SD) follow up was 3.6(0.5) years and 3.8(0.7) years in the Dexon and Prolene groups, respectively. Preoperative and postoperative performance indices based on the Gastrointestinal Quality of Life Index were similar in both groups.\n Dexon mesh may be as effective as Prolene mesh in the treatment of complete rectal prolapse. A performance index seems to be a useful tool for evaluating the outcome of patients after repair of complete rectal prolapse.", "A randomized study was performed to assess whether new technologies offer advantages over the conventional technique on the clinical and functional outcome of patients with full-thickness rectal prolapse and fecal incontinence, submitted to Altemeier's procedure with levatorplasty.\n Between January 1999 and December 2003, 58 patients (55 females; mean age, 70.9 +/- 11.3 years) with full-thickness rectal prolapse were evaluated with continence score, colonoscopy, anorectal manometry, anal electromyography, and sacral reflex latency; 40 of them were selected and randomly assigned to two groups: 20 patients (Group 1; 19 females, 73.4 +/- 10.4 years) were submitted to a conventional operation with monopolar electrocautery and handsewn anastomosis, and 20 (Group 2; 18 females, 71.5 +/- 12.2 years) using harmonic scalpel and circular stapler. Patients were followed up with clinical examination, anorectal manometry, and anal electromyography, with mean follow-up 29.3 +/- 8.5 and 27.5 +/- 9.2 months in Groups 1 and 2, respectively.\n Operative time, blood loss, and hospital stay were significantly reduced in Group 2 (P < 0.001), whereas no differences were found in pain score, time to return to normal activity, morbidity, and mortality. Complications were two (10 percent) stenosis in Group 1. Fecal continence score significantly improved in both groups (P < 0.01), whereas anorectal manometry and neurophysiologic data were not significantly modified by the operation. Recurrence rates were 15 and 10 percent in Groups 1 and 2, respectively (P= not significant).\n The clinical and functional long-term results of perineal rectosigmoidectomy with levatorplasty are not influenced by surgical instruments and type of coloanal anastomosis. The clinical relevance of the short-term results in high-risk patients should be specifically investigated.", "The introduction of new laparoscopic techniques has important cost implications. The aim of this study was to compare the cost effectiveness of laparoscopic rectopexy with that of open abdominal rectopexy for full-thickness rectal prolapse.\n A cost effectiveness study was conducted alongside a randomized trial of laparoscopic versus open abdominal rectopexy.\n The efficacy trial demonstrated significant subjective and objective differences in favour of the laparoscopic technique. The mean operating time was 51 min longer for laparoscopic rectopexy than for the open procedure. Laparoscopic disposables incurred a mean cost of pound 291 per patient. The mean duration of hospital stay was significantly shorter for the laparoscopic group (P = 0.001). Laparoscopic rectopexy was associated with an overall mean cost saving of pound 357 (95 per cent confidence interval pound 164 to pound 592; P = 0.042) per patient.\n Laparoscopic rectopexy is associated with superior clinical outcomes and is cheaper than the open approach.\n Copyright 2004 British Journal of Surgery Society Ltd." ]

[ "9652559", "18199693", "15699766", "15659136", "2157982", "16868708", "19535812", "16824149", "16827869", "17093248", "17102775", "18089329", "12095056", "14974365", "10075594", "14529854", "16861943", "17893603", "2652578", "16123718", "12591362", "12962761", "17627241", "17580147", "15446319", "12544868", "11750377", "9921806", "11602853", "12118902", "7645037", "9428817", "15848570", "11773888", "18094377", "8310508", "19398001", "8438496", "12832740", "12545341", "11498153", "16378069", "19470677", "14756266", "19034219", "15818323", "15856479", "12492710", "1846250", "19005406", "11377526" ]

[ "Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group.", "CMV infections after two doses of daclizumab versus thymoglobulin in renal transplant patients receiving mycophenolate mofetil, steroids and delayed cyclosporine A.", "Multicenter, randomized study of the effectiveness of basiliximab in avoiding addition of steroids to cyclosporine a monotherapy in renal transplant recipients.", "Steroid avoidance in renal transplantation using basiliximab induction, cyclosporine-based immunosuppression and protocol biopsies.", "Randomized controlled trial of a monoclonal antibody against the interleukin-2 receptor (33B3.1) as compared with rabbit antithymocyte globulin for prophylaxis against rejection of renal allografts.", "Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function.", "B-cell-depleting induction therapy and acute cellular rejection.", "Two-dose basiliximab compared with two-dose daclizumab in renal transplantation: a clinical study.", "A prospective, randomized, multicenter trial of tacrolimus-based therapy with or without basiliximab in pediatric renal transplantation.", "Rabbit antithymocyte globulin versus basiliximab in renal transplantation.", "High rejection rate during calcineurin inhibitor-free and early steroid withdrawal immunosuppression in renal transplantation.", "Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal graft recipients.", "Immunoprophylaxis with basiliximab compared with antithymocyte globulin in renal transplant patients receiving MMF-containing triple therapy.", "[Cytokines and growth factors serum level and renal allograft function (preliminary report)].", "Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Study Group.", "ATG versus basiliximab induction therapy in renal allograft recipients receiving a dual immunosuppressive regimen: one-year results.", "Calcineurin inhibitor avoidance with daclizumab, mycophenolate mofetil, and prednisolone in DR-matched de novo kidney transplant recipients.", "Randomized controlled study comparing reduced calcineurin inhibitors exposure versus standard cyclosporine-based immunosuppression.", "Early experience with anti-Tac in clinical renal transplantation.", "A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring.", "Randomised trial of simulect versus placebo for control of acute rejection in renal allograft recipients.", "Tacrolimus-Basiliximab versus Cyclosporine-Basiliximab in renal transplantation \"de novo\": acute rejection and complications.", "Single bolus antithymocyte globulin versus basiliximab induction in kidney transplantation with cyclosporine triple immunosuppression: efficacy and safety.", "A single-dose daclizumab induction protocol in renal allograft recipients: a Chinese single center experience.", "Sequential protocols using basiliximab versus antithymocyte globulins in renal-transplant patients receiving mycophenolate mofetil and steroids.", "Randomized double-blind study of immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with mycophenolate mofetil-containing triple therapy in renal transplantation.", "Low rate of acute rejection and cytomegalovirus infection in kidney transplant recipients with basiliximab.", "Reduction of acute renal allograft rejection by daclizumab. Daclizumab Double Therapy Study Group.", "A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients.", "Limited dose monoclonal IL-2R antibody induction protocol after primary kidney transplantation.", "A double-blind, placebo-controlled study of monoclonal anti-interleukin-2 receptor antibody (BT563) administration to prevent acute rejection after kidney transplantation.", "Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group.", "Basiliximab (Simulect) reduces acute rejection among sensitized kidney allograft recipients.", "Basiliximab versus antithymocyte globulin for prevention of acute renal allograft rejection.", "Reduced exposure to calcineurin inhibitors in renal transplantation.", "Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. II. Results after a second kidney transplantation.", "Clinical rejection and persistent immune regulation in kidney transplant patients.", "Prophylactic use of the anti-IL-2 receptor monoclonal antibody LO-Tact-1 in cadaveric renal transplantation: results of a randomized study.", "Basiliximab reduces the incidence of acute cellular rejection in live-related-donor kidney transplantation: a three-year prospective randomized trial.", "Safety and efficacy of an alternative basiliximab (Simulect) regimen after renal transplantation: administration of a single 40-mg dose on the first postoperative day in patients receiving triple therapy with azathioprine.", "Induction immunosuppression with interleukin-2 receptor antibodies (basiliximab and daclizumab) in renal transplant recipients.", "Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study.", "Daclizumab versus antithymocyte globulin in high-immunological-risk renal transplant recipients.", "Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation.", "ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial.", "Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation.", "Randomized clinical trial of daclizumab induction and delayed introduction of tacrolimus for recipients of non-heart-beating kidney transplants.", "Pharmacokinetic and pharmacodynamic studies of one or two doses of daclizumab in renal transplantation.", "A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation.", "Efficacy and safety of basiliximab in pediatric renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.", "Zenapax versus OKT-3 prophylaxis in immunologically high-risk kidney transplant recipients." ]

[ "Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients.\n 380 adult recipients of a primary cadaveric kidney transplant were randomly allocated, in this double-blind trial, to receive a 20 mg infusion of basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study. The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation. Safety and tolerability were monitored over the 12 months of the study.\n 376 patients were eligible for intention-to-treat analysis (basiliximab, n=190; placebo, n=186). No significant differences in patient characteristics were apparent. The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73 (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At weeks 2 and 4 post-transplantation, the mean daily dose of steroids was significantly higher in the placebo group (p<0.001 with one-way analysis of variance). The incidence of graft loss at 12 months post-transplantation was 23 (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and other adverse events was similar in the two treatment groups. The acute tolerability of basiliximab was excellent, with no evidence of cytokine-release syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%], p=0.293) occurred during the 12-month study and a further three deaths (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One post-transplantation lymphoproliferative disorder was recorded in each group.\n Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly, with no clinically relevant safety or tolerability concerns.", "Cytomegalovirus (CMV) infection is a major complication after renal transplantation and is involved in graft rejection. The anti-interleukin-2-receptor antibody daclizumab reduces the incidence of acute rejection without increasing the incidence of CMV infection.\n This multicentre, randomized trial compared safety and efficacy, at 1 year, of two doses of daclizumab (54 patients, group D) with thymoglobulin (55 patients, group T) plus delayed cyclosporine (CsA), MMF (mycophenolate mofetil) and steroids in first cadaver kidney transplant patients. Primary criterion was CMV infection/syndrome/disease. D+/R- patients received oral ganciclovir prophylaxis for 90 days.\n Status for CMV was identical in the both groups. The incidence of CMV infection/syndrome/disease was 39% in group D versus 51% in group T (NS). Time to onset of CMV replication was delayed in group D (P = 0.015) and mean number of pp65-positive cells was lower at 4 and 6 months (P < 0.001). Incidence of symptomatic CMV episodes was not reduced in whole group D (5.6% versus 16.4%, NS), but lower in D+/R+ and D-/R+ patients without chemoprophylaxis, compared to group T (2.8% versus 21.6%, P = 0.028). Patient and graft survivals and incidence of biopsy-proven acute rejection were identical.\n Limited dosing regimen of daclizumab with MMF, steroids and delayed CsA introduction was safe and effective. The incidence of CMV infection was not significantly different, but without chemoprophylaxis, clinical manifestations and viral replication were reduced with this regimen.", "Steroid therapy is associated with an increased risk of cardiovascular events and well-documented adverse effects, but two thirds of patients initiated on monotherapy with cyclosporine A (CsA) microemulsion require addition of steroids.\n In this 12-month randomized, double-blind, multicenter study, 108 renal transplant recipients were randomized and received basiliximab (n=52) or placebo (n=56) to assess whether basiliximab reduces the need for addition of steroids or other adjunctive immunosuppressive drugs to CsA monotherapy.\n The primary endpoint of the study (requirement for additional immunosuppression at 12 months posttransplant) occurred significantly less frequently with basiliximab (54%) than placebo (73%) (P=0.046). By the end of the study, 25% of basiliximab-treated patients were receiving maintenance steroids versus 61% of placebo-treated patients (P=0.0006). During the trial, 33% of basiliximab-treated patients received oral steroids at some time compared with 61% of placebo-treated patients (P=0.004). The proportion of patients experiencing biopsy-proven rejection was not significantly different between the basiliximab (29%) and placebo (43%) groups (P=0.16). Median serum creatinine at 12 months was 141 mumol/L with basiliximab and 164 mumol/L with placebo (not significant). One-year graft and patient survivals were 88% and 98% for basiliximab and 88% and 96% for placebo (not significant), respectively. Adverse events were similar in the basiliximab and placebo treatment groups.\n These findings demonstrate that the addition of basiliximab significantly reduces the need to modify the initial treatment regimen in patients scheduled to receive steroid-free CsA therapy, suggesting that basiliximab induction may be useful as a strategy in other steroid-avoidance regimens.", "Reducing chronic steroid exposure is important to minimize steroid-related morbidity, particularly for susceptible renal transplant recipients. Steroid-free and steroid-sparing protocols have shown benefits, but safety has not been established for all populations. We investigated the safety of steroid avoidance (SA) in a population including African-Americans, using modern immunosuppression with protocol biopsy monitoring.\n A randomized-controlled SA trial (early discontinuation, days 2-7) was conducted in a population (n = 77) including African-Americans and cadaveric kidney recipients. Patients received basiliximab, cyclosporine (CsA), and mycophenolate mofetil (MMF). In controls, steroids were tapered to 5 mg prednisone/d by day 30. Protocol biopsies were performed (1, 6, 12 and 24 months) to evaluate subclinical acute rejection (SCAR) and chronic allograft nephropathy (CAN).\n The SA did not result in significantly higher incidences of graft loss, AR, SCAR, CAN, or renal fibrosis. SA patients experienced similar renal function, comparable serum lipid levels, and a trend toward fewer cases of new-onset diabetes. Clinical outcomes of African-American and non-African-American patients did not significantly differ.\n The SA is safe in the context of basiliximab induction and CsA-based immunosuppression. This protocol could minimize steroid-related side effects in susceptible groups, including African-Americans, without increasing the risk of AR or graft failure.", "Interleukin-2 is a major growth factor for activated T lymphocytes, and antibodies reacting with the Tac-chain component of the interleukin-2 receptor can prevent allograft rejection in animals. Because Tac chains are expressed only on a small fraction of activated lymphocytes, monoclonal antibodies against the interleukin-2 receptor may offer a more specific means of immunosuppression than polyclonal antilymphocyte globulin in prophylaxis against graft rejection. Therefore, we compared the immunosuppressive effect of 33B3.1, a rat monoclonal antibody against the human Tac chain, with the effect of a rabbit polyclonal antithymocyte globulin in a randomized study of 100 recipients of first renal transplants. Injections of 33B3.1 (10 mg per day) were tolerated well, whereas major side effects in 15 of 47 patients (32 percent) receiving antithymocyte globulin required discontinuation of treatment before day 14. The incidence of rejection episodes was not statistically different in the two groups at days 14, 30, 60, and 90 after transplantation. Patient and graft survival was also equal in the two groups at one year (96 and 85 percent, respectively, in both groups), and graft function was similar. The total number of infectious episodes within the first three months was lower in the 33B3.1 group than in the antithymocyte group (47 vs. 72). The drop in peripheral-blood lymphocyte concentrations was significantly larger in the patients treated with antithymocyte globulin. The level of circulating Tac-chain-bearing lymphocytes remained below 1 percent during 33B3.1 treatment, as compared with 4 to 5 percent during antithymocyte-globulin treatment (P not significant). We conclude that 33B3.1 is as effective as antithymocyte globulin in the prevention of renal-transplant rejection, and its use results in fewer infections and side effects.", "Reactive oxygen species (ROS) are important mediators of cellular damage and lipid peroxidation is the most important expression of ROS-induced oxidative stress. Recent studies have suggested that increased plasma malondialdehyde (MDA) levels are a consequence of specific immunosuppressive therapies. This study aims at investigating the relation between oxidative stress and immunosuppressive therapies in renal transplant patients with stable renal function and uneventful postoperative course.\n The study group included 26 renal patients. Two groups of renal transplant recipients, treated with a different combination of immunosuppressive agents were studied (Group A: CyA, MMF, Steroids and Basiliximab, Group B: Tacrolimus, MMF, Steroids and Daclizumab). All patients had an uneventful postoperative course. Plasma MDA levels were measured before transplantation, 1 and 6 months after. Plasma concentration of endogenous creatinine (Cr) was used as a measure of stable renal function.\n Levels of MDA were increased before the transplantation in all renal patients (MDA: 7.81 +/- 4.81, normal levels: 2.23-4.08 nmol/ml, P < 0.05). Combined therapy with CyA was associated with high values of MDA at 6 months measurement after transplantation. However this tendency of increased MDA levels did not achieve a statistical significance (Group A: 6.97 vs. 9.06 nmol/ml, P>0.05). On the contrary, statistically significant diminution of MDA levels was observed in Group B patients (Tacrolimus-MMF-steroids) at 6 months measurement after transplantation. (Group B: 8.61 vs. 4.11 nmol/ml, P<0.02<0.05).\n Immunosuppressive combined therapy with CyA was associated with the high values of MDA that were measured posttransplantly. Our study provides strong evidence that Tacrolimus is significantly associated with improved free radical metabolism.", "nan", "Addition of the interleukin-2 receptor (IL-2R) antagonists basiliximab or daclizumab to a calcineurin inhibitor-based regimen significantly reduces risk of acute rejection with a tolerability profile similar to a placebo. Use of a truncated two-dose regimen of daclizumab has been reported, but till date, there has been no controlled study of two-dose daclizumab vs. two-dose basiliximab.\n Deceased-donor renal transplant recipients were randomized to basiliximab (20 mg on days 0 and 4) or daclizumab (50 mg on days 1 and 14) with cyclosporine, mycophenolate mofetil and corticosteroids. Flow cytometry was used to calculate the proportion of CD25(+) T cells in peripheral blood.\n Thirty patients were randomized to basiliximab and 28 to daclizumab. There was one patient death in each group, with no other graft losses. By six months, the incidence of biopsy-proven acute rejection was 0% with basiliximab vs. 21.4% with daclizumab (p < 0.05). Three patients in the daclizumab group required OKT3 for steroid-resistant rejection. There were no between-group differences in the incidence of infection. The proportion of CD25(+) T cells declined markedly during the first two wk in both groups, but was significantly lower in the basiliximab group during weeks six to eight.\n Two doses of basiliximab are more effective than two 1 mg/kg doses of daclizumab in preventing acute rejection in de novo renal transplant patients receiving cyclosporine, mycophenolate mofetil and corticosteroid maintenance therapy. In patients receiving relatively low-level immunosuppression in order to minimize toxicity, basiliximab may be preferable to a truncated daclizumab regimen.", "In a 6-month, multicenter, randomized, controlled, open-label, parallel-group trial, we investigated the efficacy and safety of adding basiliximab to a standard tacrolimus-based regimen in pediatric renal transplant recipients. Patients < 18 years received tacrolimus/azathioprine/steroids (TAS, n = 93) or tacrolimus/azathioprine/steroids/basiliximab (TAS + B, n = 99). Target tacrolimus levels were 10-20 ng/mL between days 0-21 and 5-15 ng/mL thereafter. Steroid dosing was identical in both groups. Basiliximab was administered at 10 mg (patients < 40 kg) or 20 mg (patients > or = 40 kg) within 4 h of reperfusion; the same dose was repeated on day 4. Biopsy-proven acute rejection rates were 20.4% (TAS) and 19.2% (TAS + B); steroid-resistant acute rejection rates were 3.2% and 3.0%, respectively. Patient survival was 100%; graft survival rates were 95% in both arms. The nature and incidence of adverse events were similar in both arms except toxic nephropathy and abdominal pain, which were significantly higher in the TAS + B arm (14.1% vs. 4.3%; p = 0.03 and 11.1% vs. 2.2%; p = 0.02; respectively). Median serum creatinine concentrations at 6 months were 86 micromol/L in the TAS and 91 micromol/L in the TAS + B arm; glomerular filtration rate was 79.4 and 77.6 (mL/min/1.73 m2), respectively. Adding basiliximab to a tacrolimus-based regimen is safe in pediatric patients, but does not improve clinical efficacy.", "Induction therapy reduces the frequency of acute rejection and delayed graft function after transplantation. A rabbit antithymocyte polyclonal antibody or basiliximab, an interleukin-2 receptor monoclonal antibody, is most commonly used for induction.\n In this prospective, randomized, international study, we compared short courses of antithymocyte globulin and basiliximab in patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor. Patients taking cyclosporine, mycophenolate mofetil, and prednisone were randomly assigned to receive either rabbit antithymocyte globulin (1.5 mg per kilogram of body weight daily, 141 patients) during transplantation (day 0) and on days 1 through 4 or basiliximab (20 mg, 137 patients) on days 0 and 4. The primary end point was a composite of acute rejection, delayed graft function, graft loss, and death.\n At 12 months, the incidence of the composite end point was similar in the two groups (P=0.34). The antithymocyte globulin group, as compared with the basiliximab group, had lower incidences of acute rejection (15.6% vs. 25.5%, P=0.02) and of acute rejection that required treatment with antibody (1.4% vs. 8.0%, P=0.005). The antithymocyte globulin group and the basiliximab group had similar incidences of graft loss (9.2% and 10.2%, respectively), delayed graft function (40.4% and 44.5%), and death (4.3% and 4.4%). Though the incidences of all adverse events, serious adverse events, and cancers were also similar between the two groups, patients receiving antithymocyte globulin had a greater incidence of infection (85.8% vs. 75.2%, P=0.03) but a lower incidence of cytomegalovirus disease (7.8% vs. 17.5%, P=0.02).\n Among patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor, induction therapy consisting of a 5-day course of antithymocyte globulin, as compared with basiliximab, reduced the incidence and severity of acute rejection but not the incidence of delayed graft function. Patient and graft survival were similar in the two groups. (ClinicalTrials.gov number, NCT00235300 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.", "Morbidity and mortality due to cardiovascular disease are major problems after renal transplantation. The effects of three immunosuppressive protocols on cardiovascular end points were investigated in a single-center, randomized, parallel (1-1-1) group. Acute rejection was a secondary safety endpoint. Groups were as follows: group one, tacrolimus+sirolimus; group two, tacrolimus+mycophenolate mofetil (MMF); group three, sirolimus+MMF+daclizumab. All groups received two days methylprednisolone only. The Ethical Committee demanded an interim analysis when 50% of the patients were included. In this analysis, 54 patients with a median follow-up of 9.2 months were studied. The Kaplan-Meyer analysis showed a difference in rejection free survival between group one (82%) and group three (34%, P=0.03) and between groups one and two (tacrolimus-based, 76%) and group three (calcineurin-free, 34%, P=0.04). Calcineurin-free immunosuppression with two days of steroids only showed an unacceptable high incidence of acute rejection and re-rejection, and the study had to be stopped.", "In this prospective, randomized, open-label, single-center study, we compared the efficacy and safety of two anti-interleukin-2 receptor monoclonal antibodies among adult recipients of at least 1 HLA-mismatched deceased donor renal grafts. Eligible patients were randomized to induction with either basiliximab or daclizumab. Both groups received cyclosporine microemulsion (CsA Neoral), mycophenolate mofetil, and methylprednisolone. An intent-to-treat analysis of 1-year data assessed the incidence of acute rejection episodes, the renal graft function, the safety, and the patient and graft survivals. Among 127 patients, six (10.0%) and seven (11.5%) patients experienced biopsy-confirmed acute rejection at 12 months, in the basiliximab and the daclizumab groups, respectively. Two renal grafts were lost in the basiliximab and six in the daclizumab cohort, one of them due to rejection. One basiliximab and two daclizumab patients died. Hospital treatment was required for 25 and 33 infections in basiliximab and daclizumab groups, respectively. One basal cell carcinoma of skin was detected. One hypersensitivity reaction was observed with daclizumab. At 12 months, serum creatinine was 101+/-28 micromol/L with basiliximab and 109+/-41 micromol/L with daclizumab. Patient survival was 98.4% with basiliximab and 96.7% with daclizumab, and graft survival was 96.8% versus 90.8%, respectively. No significant differences were observed between the groups. Basiliximab or daclizumab combined with triple therapy was an efficient and safe immunosuppression strategy, demonstrated with low incidence of acute rejection episodes, an acceptable adverse event profile, excellent graft function, and high survival rates in adult recipients within the first year after deceased donor renal transplantation.", "Acute graft rejection remains a major problem in renal transplant recipients, and there is no consensus on the optimal immunosuppressive strategy. Immunoprophylaxis with Thymoglobulin or basiliximab has significantly reduced the incidence of acute rejection episodes and graft loss following kidney transplantation. This open, randomized, multicenter study investigated the efficacy and tolerability of basiliximab (20mg day 0-day 4) plus early cyclosporine from day 0 (n = 50) compared with Thymoglobulin plus delayed cyclosporine (n = 50) in adult kidney transplant patients. In addition, all patients received steroids and mycophenolate mofetil (MMF) at standard doses from day 0. Patient and graft survival rates at 12 months were 98 and 94% in the basiliximab group, respectively, compared with 100 and 96% in the Thymoglobulin' group. The incidences of biopsy-confirmed acute rejection (8.0% in each group) and treatment failure (14% in the basiliximab group vs. 8% in the Thymoglobulin group) were comparable in the two groups. There was a non-significant tendency to more dialysis (14 vs. 6%), and fewer cytomegalovirus (CMV) infections (p = 0.005) in the basiliximab group, but the percentage of clinical CMV was not different between the two groups (6 vs. 12%). Both strategies give excellent results, despite the differences in patterns, in nonhyperimmunized patients receiving their first cadaveric renal allograft.", "Long-term cyclosporine nephrotoxicity, subclinical rejections are risk factors of chronic allograft nephropathy. In a prospective, randomized study 44 pts. were randomized either to a reduced dose of CyA and daclizumab (group A, n = 22) or to a normal dose of CyA without daclizumab (group B, n = 22). Both groups were treated with MMF and prednisone. Number of rejection episodes was the primary endpoint. The secondary endpoints were renal function; histological parameters related to CyA; serum level of TGF-beta, PDGF-BB, blockade of CD25 molecule and surface expression of CD3, CD4, CD8, CD69, CD11a, CD49d, CD28, CD152 molecules in the subpopulations of T cells in the peripheral blood. A low incidence of clinically suspected rejection episodes were observed (19% in group A and 12.4% in group B; NS). The protocol biopsies at 3 month emerged 7 subclinical rejection episodes (4 in group A and 3 in group B). Serum creatinine level did not differ between examined groups. Chronic histopathologic changes related to CyA progressed significantly at the 3 month biopsies in both groups (with no differences between groups). Serum TGF-beta, PDGF did not differ between groups. Expression of CD25, CD152 molecule was significantly lower in group A than in group B. Immunosuppression regiment with low CyA dose with daclizumab, MMF, prednisone seems to be efficient and safe in low-risk rejection kidney allograft recipients.", "A double-blind, placebo-controlled phase III study was performed to assess whether basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, reduced the incidence of acute rejection episodes in renal allograft recipients.\n A total of 348 patients were randomized into two demographically matched, equally sized groups treated with either basiliximab or placebo. The dose of basiliximab-20-mg infusions on day 0 and day 4-was selected to block detection of interleukin-2 receptor on 97% of peripheral blood lymphocytes for 30-45 days. All patients received immunosuppressive therapy with cyclosporine microemulsion (Neoral) and steroids. An intent-to-treat analysis of 1-year data assessed the incidence of posttransplant acute rejection episodes, patient and graft survival rates, and the safety and tolerability of basiliximab.\n Among the eligible 346 patients equally divided into the two treatment groups, basiliximab reduced the proportion of patients who experienced biopsy-confirmed acute rejection episodes by 28%: 61 (35.3%) basiliximab vs. 85 (49.1%) placebo (P=0.009). Graft losses occurred in 9 (5.2%) basiliximab-treated and 12 (6.9%) placebo-treated patients. Five (2.9%) deaths in the basiliximab group and seven (4.0%) in the placebo group occurred. Compared with placebo, a higher fraction of basiliximab patients produced urine in the operating room, and a significantly lower fraction had renal dysfunction in the first month (serum creatinine > or =5 mg(dl) and between 1 and 12 months (serum creatinine > or =3 mg/dl). During the first 12 months, 94 (54%) basiliximab-treated patients experienced serious adverse events, compared with 106 (61%) who received placebo.\n Prophylactic basiliximab therapy is well tolerated, has an adverse event profile comparable to placebo, and significantly reduces the number of acute rejection episodes in renal allograft patients within the first year after transplantation.", "nan", "Calcineurin inhibitor (CNI)-free regimens posttransplantation have been claimed to conserve graft function in addition to reduce the risk factors for cardiovascular and malignant disease in renal transplant recipients.\n The primary aim of this prospective, open-label, randomized, parallel-group, single-center study was to compare the effect of complete CNI-avoidance posttransplant (daclizumab + mycophenolate mofetil + prednisolone: Dac-group, n=27) with the standard CNI-based immunosuppressive protocol at our transplant unit (cyclosporine A + mycophenolate mofetil + prednisolone: CsA-group, n=27) on renal function (glomerular filtration rate [GFR] determined as plasma clearance of 51Cr-EDTA) in a selected low immunogenic risk population (DR-matched, PRA-negative de novo cadaveric transplant recipients).\n There were no significant difference in GFR at week 10 (P=0.61), but GFR was significantly (P=0.029) lower in the Dac-group (52+/-20 ml/min) at month 12 than in the CsA-group (69+/-29 ml/min). One-year patient and graft survival did not differ between the two groups. Overall acute rejection rate was 70.4% (19/27) in the Dac-group and 29.6% (8/27) in the CsA-group (P=0.006).\n The strategy to select DR-matched, PRA-negative de novo cadaveric transplant recipients for a CNI-avoidance protocol was not successful. The incidence of acute rejection was unacceptable high even though anti-CD25 antibody induction as well as initial higher mycophenolate mofetil doses (3 g/day) were applied, and renal function was significantly lower in the CNI-avoidance patients at 1 year. Other strategies need to be examined for avoidance of CNI's in the early posttransplant period.", "Immunosuppressive regimens based on low doses of cyclosporine A (CsA) or tacrolimus (TAC) may improve short-term outcome after kidney transplantation (KT), but the optimal immunosuppressive protocol is currently unknown.\n This study compared the 24-month efficacy and safety of two immunosuppressive regimens using reduced calcineurin inhibitors (CNIs) exposure with standard dosage of CsA in 240 patients who were randomized into three groups: group A (n=80): Thymoglobulin, CsA (4 mg/kg twice daily) plus azathioprine (1.5 mg/kg once daily); group B (n=80): basiliximab, CsA (2 mg/kg/ twice daily) plus mycophenolate mofetil (MMF; 1 g twice daily); and group C (n=80): basiliximab, TAC (0.05 mg/kg/ twice daily) plus MMF (1 g twice daily). Steroid administration was identical for all groups.\n A significantly better creatinine clearance at 12 months, estimated by Cockcroft-Gault (57+/-12, 65.2+/-20, 73.5+/-27 ml/min, P=0.044), the Jelliffe-2 (51.5+/-16, 56+/-19, 59.4+/-19 ml/min/1.73 m2, P=0.041) and the Modification of Diet in Renal Disease equations (53+/-17, 58.5+/-20, 61.6+/-22 ml/min/1.73 m2, P=0.035), was observed in group C compared with group A. No significant differences were observed between groups B and C. The incidence of biopsy-proven acute rejection was similar between groups (15%, 13.8%, and 16.3%). In addition, patient and graft survival at 24 months were not different between groups. Adverse effects were similar among groups, but cytomegalovirus infections was significantly higher in group A (41% vs. 20% vs. 25%; P=0.008).\n Immunosuppressive regimens with reduced CNI exposure provide similar preservation of renal function compared with standard dose of CsA after KT and do not lead to underimmunosuppression.", "nan", "New trends in immunosuppression in clinical transplantation include the use of antibody induction agents in protocols that emphasize reduction or avoidance of steroids and calcineurin inhibitors.\n In a randomized trial using three different antibody induction agents in 90 first renal transplant recipients from cadaver donors, group A received Thymoglobulin, group B received Alemtuzumab, and group C received Daclizumab. Maintenance immunosuppression included tacrolimus and mycophenolate in all three arms, and methylprednisolone in groups A and C only (standard clinical institutional practice). The targeted trough level of tacrolimus was between 8 and 10 ng/mL for groups A and C, respectively, with a targeted mycophenolate dose of 1 g twice daily. However, in group B, the target tacrolimus trough level was 4 to 7 ng/mL to reduce long-term nephrotoxicity, with 500 mg twice-daily doses of mycophenolate, without steroid maintenance.\n In this 15-month median postoperative interval report, there were no notable differences in demographics and patient and graft survivals. Acute rejection rates at 1 year were equivalent, that is, 5 of 30 in all three groups (16.6%). In group B, there was slightly lower renal function at 1 month, but no difference at 1 year. There was also significantly more leukopenia, but a greater percentage of T-regulatory cells and number of Fox-P3 mRNA copies by flow cytometry and semiquantitative polymerase chain reaction analysis, respectively, in group B.\n This preliminary analysis indicates that 80% of the patients in group B remained steroid-free 1 year postoperatively, with lower tacrolimus trough levels and no difference in other adverse events.", "nan", "Optimal immunosuppression is essential to maintain kidney allograft viability but minimizing toxicity is also fundamental.\n This article compares immunosuppressants, corticosteroids, cyclosporine, tacrolimus, and basiliximab, which are used in the treatment regimens for renal transplantation. The analyses evaluated their effectiveness to prevent acute rejection episodes and to reduce the appearance of other complications, mainly infectious disease complications.\n Ninety-five patients were analysed during the first year after primary renal transplantation. These patients were included in a random way in 3 different groups according to the immunosuppressant drug therapy: Group I (35 patients) received corticosteroids + CsA; Group II (35 patients) received corticosteroids + CsA + Basiliximab; Group III (25 patients) received corticosteroids + Tacrolimus + Basiliximab.\n Among the 95 patients, 9 presented with an acute rejection episode in Group I. None in Group II, and one in group III. With reference to the infectious disease complications, the incidence of oral herpes was one case in Group I, 4 cases in Group II, and 2 cases in group III.\n Treatment with Basiliximab produced a significantly lower incidence of acute rejection cases and an increase in infectious disease complications, such as lip herpes.", "The aim of this prospective randomized study was to examine the effect of induction immunosuppression and low initial cyclosporine (CsA) on the onset of graft function and its long-term consequences.\n During 1999-2001, 155 patients were randomized to single 9 mg/kg dose antithymocyte globulin (ATG)-Fresenius (group A) or two 20-mg doses of basiliximab (group B) with reduced dose CsA or conventional CsA triple therapy without induction (group C).\n Delayed function (DGF) was lower in group A than in groups B or C (5.7% vs. 24.1% and 15.9%, P<0.025) and need of dialysis was less in groups A and B compared to C (10.3 and 10.4 vs. 20.0 days, P<0.05). Acute rejections occurred in 11.3%, 12.1% and 20.5%, and the mean (median) time to rejection was 16 (13), 97 (46) and 101 (35) days in groups A, B, and C, respectively (P<0.005). One-and 5-year graft survivals (GS) were 98.1% and 90.6% (group A), 96.6% and 96.6% (group B), and 93.2% and 84.1% (group C). Five-year GS was significantly better in group B than in group C (P<0.05). The death censored 5-year GS in groups A, B, and C were 94.3%, 96.6%, and 90.0% (P=NS). Single high-dose ATG induction was associated with hemodynamic and pulmonary disturbances without, however, serious or long-term consequences.\n ATG induction significantly reduced DGF. Both induction regimens together with low initial CsA led to significantly less posttransplant dialysis and excellent survival. The high dose ATG was associated with significant hemodynamic and pulmonary side effects during drug infusion.", "This study prospectively compared immunoprophylaxis with a single dose of daclizumab versus no induction in kidney transplant recipients treated with a cyclosporine, mycophenolate mofetil, and prednisone-based immunosuppression regimen seeking to observe the impact of a single-dose regimen for prevention of acute rejection among Chinese renal allograft recipients. A total of 118 renal transplant recipients were randomized into a daclizumab induction therapy group (daclizumab group, n = 58) and a no induction group (control group, n = 60). The daclizumab group received a single-dose (1 mg/kg of ideal body weight by intravenous infusion) 2 hours before the operation. There was no induction therapy in the control group. There was no significant difference in the baseline parameters at randomization between the two groups. The mean time to the first episode of acute rejection was 41.2 +/- 3.2 days for the daclizumab group versus 11.2 +/- 4.6 days for the control group. The number of first biopsy-confirmed acute rejection episodes during the 6-months after transplantation was significantly different in the daclizumab (7,12.1%) versus the control group (14,23.3%; P < .001). At the end of 12 months, patient and graft survivals were 100% in the groups with or without daclizumab. We noted that the incidence of infection, including serious infection was similar, in the daclizumab group to that in the control group, 17.2% and 20.0%, respectively. This study showed that a single-dose of daclizumab effectively prevented acute rejection in Chinese renal allograft recipients.", "Sequential anti-thymocyte globulins (ATG)/cyclosporine immunosuppression has two main advantages: delayed introduction of the nephrotoxic drug cyclosporine and prevention of acute rejection. Basiliximab, a recently developed chimeric monoclonal antibody that selectively depletes the minor subpopulation of activated T lymphocytes, has been shown to reduce the incidence of acute rejection when used with cyclosporine introduced on day 1.\n This open, randomized, multicenter study was undertaken to compare the safety and efficacy of ATG versus basiliximab induction therapy (IT) with delayed introduction of cyclosporine for microemulsion (Neoral) in 105 low immunologic risk renal-transplant patients receiving mycophenolate mofetil and steroids.\n One-year patient and graft survival rates were 98.1% and 94.2%, respectively, in the basiliximab group (n = 52), and 98.1% and 96.2% in the ATG group (n = 53). The incidence of biopsy-confirmed acute rejection was comparable (basiliximab 9.6%, ATG 9.4%), as were key parameters of renal function, notably serum creatinine levels, time-to-nadir serum creatinine, and the number of patients requiring posttransplantation dialysis (basiliximab 28.8%, ATG 30.2%). However, significantly fewer patients in the basiliximab group experienced cytomegalovirus (CMV) infection, leukopenia, and thrombocytopenia, and this without any significant difference in any other key safety parameters (including the incidences of serum sickness, fever, lymphoma, and infections in general).\n Both ATG and basiliximab, when used for IT in a sequential protocol, are equally effective in terms of graft and patient survival as well as at preventing acute rejection. However, basiliximab is associated with a lower incidence of certain key adverse events, namely CMV infection, leukopenia, and thrombocytopenia.", "Acute rejection remains a major problem in renal transplantation. Immunoprophylaxis with basiliximab (Simulect) has achieved significant reductions in acute rejection episodes in renal allograft recipients receiving dual immunosuppression. This study explored the tolerability and cumulative benefit of combining basiliximab with triple-drug therapy-cyclosporine (USP Modified, Neoral), mycophenolate mofetil, and steroids.\n In a randomized, double-blind, placebo-controlled, multicenter study, 123 kidney transplant recipients received either basiliximab at 20 mg before transplantation (day 0) and 20 mg on day 4 (n=59), or placebo (n=64). All received triple-drug immunosuppression and were followed for 6 months.\n Tolerability of basiliximab was equivalent to placebo, with no increase in serious adverse events, infection, malignancy, or posttransplant lymphoproliferative disorder. At 6 months, there were trends in favor of basiliximab over placebo in the incidences of first biopsy-confirmed acute rejection (15.3% vs. 26.6%, P=NS) and of acute rejection treated with antibody (5.1% vs. 15.6%, P=NS). Kaplan-Meier estimates at 4 weeks and 6 months were significantly in favor of basiliximab treatment for first acute rejection, biopsy-confirmed rejection, rejection episodes treated with antibody therapy, and treatment failure. Renal function improved more rapidly in the basiliximab group, with mean creatinine clearance at week 2 being 54.7 mL/min versus 43.2 mL/min for placebo (P=0.034). At 12 months, patient survival was 100% in both groups; graft survival was 94.9% with basiliximab and 92.2% with placebo.\n Basiliximab immunoprophylaxis is safe, well tolerated, and shows a trend toward reduction in number of acute rejection episodes in renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.", "nan", "Acute rejection is still a major problem in renal transplantation and is one of the most important causes of chronic graft dysfunction and late graft loss. Selective immunosuppression with a humanized antibody against the alpha-chain of the interleukin (IL)-2 receptor (CD25) was evaluated to demonstrate the efficacy of this type of immunoprophylaxis in combination with dual immunosuppression.\n We studied the effect of daclizumab, a humanized monoclonal antibody against the alpha-chain of the IL-2 receptor, in a randomized double-blind, prospective phase III clinical trial in 275 patients receiving a first cadaveric renal allograft. Among them 111 (83%) in the placebo arm and 116 (82%) in the daclizumab arm received the full regimen of five doses (1.0 mg/kg) every other week. Baseline immunosuppression consisted of cyclosporine and corticosteroids.\n At 6 months, 39 (28%) of the patients in the daclizumab group had biopsy-proven rejections, as compared with 63 (47%) in the placebo group (P=0.001). The need for additional antilymphocyte therapy, antithymocyte globulin, antilymphocyte globulin (ATG, ALG, OKT3) was also lower in the daclizumab group (8% vs. 16%, P=0.02), and they required significantly lower mean (+/- SD) cumulative doses of prednisone (3750+/-1981 mg vs. 4438+/-2667 mg in the placebo group, P=0.01). Graft function was significantly better (P=0.02) in the daclizumab group (graft function rate: 58 vs. 51 ml/min, mean) as was patient survival (P=0.01, 99% vs. 94%). No specific adverse events were observed in daclizumab-treated patients. Patients receiving daclizumab experienced fewer cytomegalovirus infections (18% vs. 25%), and none died from severe infectious complications, compared to four patients in the placebo arm. No patient in the daclizumab group had a lymphoproliferative disorder or any other form of immunosuppression-related tumor during the first year after transplant.\n Administration of daclizumab in addition to dual immunosuppression therapy significantly reduced biopsy-proven acute rejection after renal transplantation, improved patient survival, and did not add to the toxicity of the immunosuppressive regimen.", "A double-blind, placebo-controlled, randomized study was performed to assess whether immunoprophylaxis with basiliximab (Simulect) could reduce the incidence of acute rejection in kidney transplant recipients treated with cyclosporine (Neoral), steroids, and azathioprine.\n Three hundred forty patients received either placebo or basiliximab at a dose of 20 mg, given intravenously on days 0 and 4. All patients received cyclosporine, steroids, and azathioprine. The primary endpoint was the incidence of acute rejection at 6 months. Secondary endpoints included the safety and tolerability of basiliximab and placebo, 1-year patient and graft survival, and significant medical events up to 12 months.\n During the first 6 months posttransplantation, acute rejection occurred in 20.8% of patients given basiliximab versus 34.9% of patients administered placebo (P=0.005). Similarly, there was a reduction in biopsy-proven acute rejection at 6 months in the patients receiving basiliximab (P=0.023). One-year patient survival was 97.6% with basiliximab and 97.1% with placebo, graft survival was 91.5% versus 88.4%, respectively (NS). The adverse-events profile of patients treated with basiliximab was indistinguishable from that of patients treated with placebo. The number of patients with infections was similar (65.5% for basiliximab vs. 65.7% for placebo), including cytomegalovirus infections (17.3% vs. 14.5%, P=0.245). Nine neoplasms (three in the basiliximab group, six in the placebo arm) were recorded up to 1 year from transplantation.\n Basiliximab in combination with cyclosporine, steroids, and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects.", "This study prospectively compared immunoprophylaxis with a single intraoperative dose (2 mg/kg) of monoclonal interleukin-2 receptor (IL-2R) antibody vs. noninduction in kidney transplant recipients treated with tacrolimus (FK 506), mycophenolate mofetil (MMF) and a prednisone-based immunosuppression regimen. One hundred recipients of first-kidney transplant were enrolled into the study to receive either anti-IL-2R monoclonal antibody, daclizumab (2 mg/kg intraoperatively, limited anti-IL-2R) or no induction (control). Each patient also received oral tacrolimus (dosed to target trough level 10-15 ng/mL), MMF (500 mg bid) and prednisone. The primary efficacy end-point was the incidence of biopsy proven acute rejection during the first 6 months post-transplant. The patients were also followed for 12-month graft function, and graft and patient survival rates. Other than the donor's age being significantly lower in the control group, both groups were comparable with respect to age, weight, gender, race, human leukocyte antigen (HLA)-DR mismatch, panel reactive antibody (%PRA), cold ischemic time, cytomegalovirus (CMV) status, causes of renal failure, and duration and modes of renal replacement therapy (RRT). During the first 6 months, episodes of first biopsy confirmed acute rejection was 3/50 (6%) in the limited anti-IL-2R group and 8/50 (16%) in the controls (p < 0.05). Twelve-month patient 100/98 (%) and graft survival 100/96 (%) were not statistically different. The group receiving limited anti-IL-2R did not have any adverse reactions. Our study demonstrates that a limited (single) 2 mg/kg immunoprophylaxis dose with monoclonal IL-2R antibody (daclizumab) when combined with tacrolimus/MMF/steroid allows significant reduction in early renal allograft rejection to the single digit level. The therapy with anti-IL-2R antibody is simple and is well tolerated.", "In a double-blind, randomized, placebo-controlled trial, BT563, a murine IgG1 anti-IL-2R antibody, was given as a rejection prophylaxis after kidney transplantation. Drug-related side effects were not observed. During the 10-day course of BT563, no rejections (0/27) were found, whereas a rejection episode occurred in 7 patients (7/29) (P = 0.01) during placebo treatment. Within the first 4 postoperative weeks, freedom from rejection in the BT563 group and in the placebo group was 96% vs. 76% (P = 0.05). Due to rejection in the placebo group, 2 grafts were lost. At 3 months, an overall rejection incidence in the BT563 and placebo group was found of 3/27 (11%) vs. 8/29 (28%) patients (P = 0.18). Infectious complications were distributed equally between the 2 groups. CMV disease, found in 3 placebo-treated patients, occurred after rejection treatment (2/3). Within the BT563 group, 1 patient lost his graft due to renal artery thrombosis, 2 grafts were lost as a result of technical failure, and 2 patients had a squamous cell carcinoma that could be treated curatively. We conclude that the use of the anti-IL-2R mAb BT563 effectively prevents rejection after kidney transplantation without increasing infectious complications.", "Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the alpha chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation.\n We administered daclizumab (1.0 mg per kilogram of body weight) or placebo intravenously before transplantation and once every other week afterward, for a total of five doses, to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine, azathioprine, and prednisone. The patients were followed at regular intervals for 12 months. The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation.\n Of the 126 patients given daclizumab, 28 (22 percent) had biopsy-confirmed episodes of acute rejection, as compared with 47 of the 134 patients (35 percent) who received placebo (P=0.03). Graft survival at 12 months was 95 percent in the daclizumab-treated patients, as compared with 90 percent in the patients given placebo (P=0.08). The patients given daclizumab did not have any adverse reactions to the drug, and at six months, there were no significant differences between the two groups with respect to infectious complications or cancers. The serum half-life of daclizumab was 20 days, and its administration resulted in prolonged saturation of interleukin-2alpha receptors on circulating lymphocytes.\n Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients.", "Our goal was to evaluate the efficacy and safety of basiliximab (Simulect) as immunosuppressive induction therapy for the prevention of acute allograft rejection among sensitized kidney recipients.\n Fifty-six adult recipients receiving cadaveric kidney transplant with panel reactive antibody class I ranging from 30% to 50% and or class II 30% to 80% were randomized at about a 2:1 ratio to the Simulect group (36 patients) or matching control group (20 patients). All patients received baseline triple immunosuppressive therapy with cyclosporine (Neoral), mycophenolate mofetil, and steroids. Simulect was given in two doses of 20 mg each on day 0 (2 hours before operation) and day 4 after transplantation.\n There was no hyperacute rejection in either group and delayed graft function occurred in three control patients. The incidence of acute rejection during the first 3 months was 11.1% in the Simulect group compared with 50% in the placebo group (77.8% reduction, P < .01). No apparent adverse and toxic events were recorded in the Simulect group. The mean daily dose of steroids was significantly higher in the control group 2 to 4 weeks posttransplantation. No clinically meaningful differences in the mean dose of cyclosporine were observed between the two groups; in addition, there were no statistically significant differences in the rate of patient or graft survival.\n On the basis of appropriate selection of the donor and recipient, Simulect is effective and safety for the sensitized recipients as immunosuppressive induction therapy.", "Basiliximab (Simulect), a high-affinity chimeric, monoclonal antibody directed against the alpha chain of human interleukin-2 receptor (CD25), reduces the incidence of acute renal allograft rejection when used in combination with cyclosporine (Neoral) and steroids. This study was designed to compare the safety and efficacy of basiliximab to polyclonal anti-T-cell (ATGAM) therapy for the prevention of acute rejection in de novo renal transplant recipients.\n This 1-year, open-label, randomized trial was conducted in recipients of cadaveric or living-related donor renal transplants. All patients received cyclosporine (Neoral), mycophenolate mofetil (CellCept, MMF), and corticosteroids. Patients who were randomized to basiliximab therapy received a 20 mg i.v. bolus dose on days 0 and 4, and the majority of patients were initiated on cyclosporine within 48 hr of transplantation. Patients who were randomized to antithymocyte globulin therapy (ATGAM, ATG) received 15 mg/day i.v. within 48 hr of transplant and continued treatment for up to 14 days; ATG was stopped once therapeutic cyclosporine blood levels were achieved. The initiation of cyclosporine use was delayed in the ATG group until renal function was established (serum creatinine <3.0 mg/dl or 50% fall from baseline).\n Of the 138 randomized patients, 135 received at least 1 dose of study medication (70 patients, basiliximab; 65 patients, ATG). Demographic characteristics were similar between the basiliximab and ATG-treatment groups. At 12 months, the rate of biopsy-proven acute rejection was 19% and 20%, respectively, in the basiliximab and ATG groups. Although the overall profile of adverse events was similar between basiliximab- and ATG-treated patients, adverse events considered by the investigators to be associated with the study drug occurred more often among patients receiving ATG (42% vs. 11% with basiliximab).\n Basiliximab combined with early initiation of cyclosporine therapy resulted in low acute rejection rates similar to those achieved with ATG combined with delayed cyclosporine. Basiliximab therapy showed an excellent safety profile, with no increases in malignancies, infections, or deaths. Based on its convenient two-dose, body-weight independent regimen and comparable effectiveness to ATG, basiliximab is an attractive choice for the prevention of acute rejection episodes in renal transplant patients.", "Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens.\n We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival.\n The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%).\n A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).\n Copyright 2007 Massachusetts Medical Society.", "The focus of progress in transplantation immunosuppression is to achieve more specific immunosuppression with monoclonal antibodies. We have already shown that the efficacy of 33B3.1, a rat monoclonal Ig2A directed against the human IL-2 receptor, was similar to that of rabbit antithymocyte globulin in the prevention of acute rejection in first kidney transplants. A similar comparative analysis has been made in 40-sec renal transplants. ATG (1 mg/kg/day) or 33B3.1 (10 mg/day) was administered during the first 10 days postgrafting in association with corticosteroids and azathioprine. Cyclosporine was introduced on day 9 and azathioprine/CsA constituted the patient's maintenance treatment after day 45. Rejection treatment consisted of equine antilymphocyte globulin in both cases and of steroid boluses when patients were under Cyclosporine. One patient in each group died. Graft survival was 90%, 85%, and 79% in the ATG group (n = 20) and 100%, 89%, and 89% in the 33B3.1 group (n = 20) at 3, 12, and 24 months, respectively. Of the ATG group patients, 45% and 40% in the 33B3.1 group had at least one rejection episode, half the episodes in the MoAb cohort occurring under 33B3.1, vs. none in the ATG group. Transplant function was similar in both groups. Viral infections appeared to be more frequent with ATG (60%) than with 33B3.1 (12%), with CMV accounting for half of these in the ATG group, and none in the MoAb group. Tolerance of both agents was good. Of the 33B3.1 recipients, 70% developed anti-33B3.1 antibodies. From these data, we conclude that this anti-IL-2 receptor MoAb seems less effective than rabbit ATG as induction treatment in second kidney transplant patients.", "We evaluated whether the regulatory function of CD4(+)CD25(high+)FoxP3(+) T-cells from patients on tacrolimus and mycophenolate mofetil (MMF) is affected by preceding steroid and anti-CD25 mAb induction therapy and whether this function is associated with rejection after kidney transplantation. Kidney recipients (N=15) were randomized to receive either anti-CD25 mAb induction (i.e., daclizumab) or steroids for 4 months. We analyzed the presence and suppressive activity of CD4(+)CD25(high+)FoxP3(+) peripheral T-cells in samples obtained at pre and 4-6 months after transplantation. Anti-CD25 mAb therapy and treatment with steroids did not significantly affect protein expression of FoxP3. However, at the functional level, significant differences were found in the regulatory activities of CD4(+)CD25(high+) T-cells from the anti-CD25 group vs those from the steroid group. At 4-6 months after transplantation, the regulatory activities of CD4(+)CD25(high+) T-cells were comparable to those before anti-CD25 mAb therapy; 49+/-13% (mean+/-SEM) vs 40+/-14% at a 1:20 ratio (CD25(high+):CD25(-/dim)), respectively. In contrast, the regulatory capacities of CD(+)D25(bright+) T-cells from the steroid patient group became significantly impaired. The percentage inhibition of the anti-donor response decreased from 57+/-12% before transplantation to 12+/-7% after transplantation (p<0.01). Five out of 15 patients experienced a rejection episode. At 4-6 months after transplantation, the CD25(high+) cells from these rejectors (who all received daclizumab induction therapy) had clear regulatory function, while suppression by CD25(high+) cells from non-rejectors (N=10) was significantly lower. The percentage inhibition of the anti-donor response was 48+/-14% (mean+/-SEM) vs 10+/-7%, respectively, p=0.02. Anti-CD25 mAb induction therapy does not negatively influence the regulatory function of CD4(+)CD25(high+)FoxP3(+) T-cells from kidney transplant recipients on tacrolimus and MMF. The majority of these patients experienced an acute rejection episode, which suggests that immune activation is required for persistent immunoregulatory function.", "nan", "The aim of this work was to investigate the benefit of basiliximab induction therapy in living-related-donor kidney transplantation.\n One hundred adult recipients of a first kidney allograft were randomized into two treatment groups, one to receive basiliximab and the second as a control. All patients received maintenance triple immunosuppressive therapy (steroids, cyclosporine microemulsion and azathioprine). The patients were followed up for a minimum of three years. The end points for evaluation included the incidence of acute rejection episodes, severity of rejection, cumulative steroid dose, patients' and graft survival.\n Basiliximab significantly reduced the proportion of patients who experienced an acute rejection in the first year (18/50) compared to the control group (31/50). At three years there were 26 acute rejections in the basiliximab group and 36 in control group. The cumulative steroid dose at three and 12 months was significantly lower in the basiliximab group. The overall incidence of post-transplant complications was comparable in the two groups.\n Prophylactic basiliximab is well tolerated and significantly reduces the incidence of acute rejection episodes in living-related-donor kidney transplantation.", "This was a multi-center, open-label, randomized, dose-comparative study on 202 renal transplantation patients. We evaluated for the first time an alternative dosing regimen for basiliximab, consisting of a single 40-mg intravenous dose on day 1 post-transplantation plus triple therapy, in comparison with the conventional two-dose regimen (2 h before transplantation and on day 4) plus triple therapy. At 6 months, the incidence of acute rejection was low: 22.5% of patients in the basiliximab 2 x 20-mg group and 20.0% of patients in the basiliximab 1 x 40-mg group experienced an acute rejection episode ( P = 0.628) (biopsy-proven rejection: 19.6% and 17.0%, P = 0.585). There was no statistically significant difference in any of the secondary efficacy parameters. The incidence of graft loss by 12 months was 4.9% and 6.0% in the 2 x 20-mg and 1 x 40-mg group, respectively ( P = 0.73). No differences were observed between the dosage groups with regards to safety assessments (adverse events (AEs), infections, vital signs, laboratory safety evaluations, and physical examinations). The data reveal that basiliximab can be safely and effectively administered as a single 40-mg dose on day 1 after renal transplantation as a therapeutic option to the established 2 x 20-mg dosing regimen. This alternative dosing regimen may be of significant convenience under circumstances when a first dose of basiliximab was not given prior to transplantation. Both regimens can conveniently be used during the initial hospitalization of the patient.", "nan", "The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy.\n This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147).\n The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively.\n Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.", "Nondepleting anti-CD25 monoclonal antibodies (daclizumab) and depleting polyclonal antithymocyte globulin (Thymoglobulin) both prevent acute rejection, but these therapies have not been directly compared in a high-risk, HLA-sensitized renal transplant population. We randomly assigned 227 patients, who were about to receive a kidney graft from a deceased donor, to either Thymoglobulin or daclizumab if they met one of the following risk factors: current panel reactive antibodies (PRA) >30%; peak PRA >50%; loss of a first kidney graft from rejection within 2 yr of transplantation; or two or three previous grafts. Maintenance immunosuppression comprised tacrolimus, mycophenolate mofetil, and steroids. Compared with the daclizumab group, patients treated with Thymoglobulin had a lower incidence of both biopsy-proven acute rejection (15.0% versus 27.2%; P = 0.016) and steroid-resistant rejection (2.7% versus 14.9%; P = 0.002) at one year. One-year graft and patient survival rates were similar between the two groups. In a comparison of rejectors and nonrejectors, overall graft survival was significantly higher in the rejection-free group (87.2% versus 75.0%; P = 0.037). In conclusion, among high-immunological-risk renal transplant recipients, Thymoglobulin is superior to daclizumab for the prevention of biopsy-proven acute rejection, but there is no significant benefit to one-year graft or patient survival.", "Daclizumab and mycophenolate mofetil (MMF) decrease the incidence of acute allograft rejection. This double-blind, randomized, placebo-controlled trial was performed primarily to assess the pharmacokinetics of MMF in an immunosuppressive regimen incorporating daclizumab. At five centers, 75 renal transplant recipients were randomized 2:1 to receive either daclizumab 1 mg/kg or placebo pre-transplantation and every other week, for a total of five doses. All patients received cyclosporine, steroids, and MMF. Levels of mycophenolic acid (MPA), its glucuronide metabolite, and daclizumab were measured after dosing on days 28 and 56. Safety parameters evaluated included: adverse events, laboratory abnormalities, infections, patient/graft survival, incidence of lymphoproliferative disorders, and incidence of acute rejection at 12 months. The concomitant administration of daclizumab and MMF had no effect on the pharmacokinetics of MPA: AUC(0-8) values (microg h/mL +/- SD) on day 28 were 30.1 +/- 13.3 for daclizumab-treat patients vs. 31.1 +/- 12.4 for placebo and on day 56, 37.7 +/- 18.2 for daclizumab-treated patients vs. 35.7 +/- 14.0 for placebo. Adverse events were similar between the two groups. Acute rejection at 12 months occurred in 14% of patients receiving daclizumab and 20% of patients receiving placebo. The coadministration of daclizumab did not result in a pharmacokinetic interaction with MPA, the active metabolite of MMF.", "Despite all the advantages in the immunosuppressive therapy, kidney transplantation in immunologically high risk patients remains a challenge. Ideally, an induction therapy should provide maximal graft protection, while adverse events rate and costs remain as low as possible.\n Immunologically high risk kidney recipients with CDC-PRA ł 25% within the last 3 years, a positive B-cell CDC-crossmatch or graft loss due to rejection within 3 years following a prior transplantation, were randomized 1:1 to receive ATG-Fresenius (ATG-F) (9 mg/kg day 0; 3 mg/kg day 1-4) or Daclizumab therapy (1 mg/kg day 0, 14, 28, 42, 56) in a pilot study. Additional immunosuppression consisted of cyclosporine, mycophenolate mofetil, and steroids. 11 patients were included in each group.\n The patient (90% in ATG-F; 100% in Daclizumab) and graft survival (censored for death) (100% in ATG-F; 90% in Daclizumab) and the mean creatinine concentration at 24 months (139+/-68 mol/l in ATG-F; 176+/-103 mol/l in Daclizumab) were similar in both groups. More severe graft rejections (3 vascular rejections in Daclizumab) and adverse events (5.3/patient in ATG-F; 6.7/patient in Daclizumab) were observed in the Daclizumab group. The costs for hospitalization/ day within 24 months were lower in ATG-F (2.32+/-3.51 USD vs. 12.25+/-9.75 USD; p=0.02) resulting in an average cost-difference of more than 10'435 USD /patient.\n In this pilot trial, both treatments were comparably successful regarding graft and patient outcome.", "Corticosteroid-free maintenance immunosuppression after organ transplantation eliminates the well-known corticosteroid-related side effects and may help to improve long-term outcome. We investigated whether a corticosteroid-free tacrolimus (Tac)/mycophenolate mofetil (MMF) regimen, in combination with daclizumab (Dac) induction therapy, provides adequate immunosuppression after renal transplantation.\n This 6-month, open-label, multicenter, parallel-group study involved 538 renal patients randomized (1:1) to a Dac/Tac/MMF regimen (n = 260) or a Tac/MMF/corticosteroids regimen (n = 278) as a control group.\n Of the patients who completed the study, 88.8% in the Dac/Tac/MMF group were free from corticosteroid therapy at month 6. The incidence of biopsy-proven acute rejection was 16.5% in both treatment groups; the incidence of biopsy-proven corticosteroid-resistant acute rejection was 4.3% and 5.0% with Tac/MMF/corticosteroids and Dac/Tac/MMF, respectively (P = NS for both comparisons). Renal function was also similar in both groups: median serum creatinine at month 6 was 125.0 micromol/L (Tac/MMF/corticosteroids) and 131.0 microml/L (Dac/Tac/MMF), P = 0.277. The overall safety profile was similar with both regimens. However, compared with the Tac/MMF/steroid regimen, a significantly reduced incidence of new-onset insulin-dependent diabetes mellitus (5.4% vs. 0.4%, P = 0.003) was found with steroid-free immunosuppression. Moreover, mean total cholesterol concentrations increased from baseline in the Tac/MMF/corticosteroids group by 0.19 mmol/L, whereas in the Dac/Tac/MMF group, levels decreased by 0.19 mmol/L, P = 0.005.\n Corticosteroid-free immunosuppression with a Dac/Tac/MMF regimen is as effective at preventing acute rejection after renal transplantation as a standard triple regimen of Tac/MMF/corticosteroids. Furthermore, the safety benefits reported with Dac/Tac/MMF treatment may help improve the long-term outcome for renal-transplant patients.", "Kidneys from non-heart-beating donors (NHBDs) have high rates of delayed graft function (DGF). Use of calcineurin inhibitors is associated with a reduction in renal blood flow, which may delay graft recovery from ischaemic acute tubular necrosis.\n To assess whether daclizumab (DZB) could safely replace tacrolimus in the immediate postoperative period, patients were randomized to receive DZB induction and daily mycophenolate mofetil with steroids (DZB group) or standard tacrolimus-based triple therapy (control group). Tacrolimus was given to patients in the DZB group when the serum creatinine level dropped below 350 micromol/l.\n Fifty-one patients were recruited at two centres over a 2-year interval between 2000 and 2003. The overall rate of immediate function was 28 per cent (13 of 46 grafts), with the highest rate in recipients of machine-perfused kidneys treated with DZB (eight of 15 patients).\n Induction with DZB and delayed introduction of tacrolimus reduced the incidence of DGF in recipients of machine-perfused NHBD kidneys.\n Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "In phase III trials daclizumab was used in a five-dose regimen of 1 mg/kg at 2-weekly intervals, resulting in saturation of IL-2Ralpha on circulating lymphocytes for up to 120 days after renal transplantation. The purpose of this study was to evaluate daclizumab blood concentrations and the saturation of the IL-2Ralpha on the circulating lymphocytes with a limited dosing regimen of daclizumab. Twelve patients undergoing primary cadaver or living donor transplantation were randomized to either receive one dose (2 mg/kg) or two doses (2nd dose, 1 mg/kg) of daclizumab in addition to maintenance immunosuppression therapy consisting of either tacrolimus or cyclosporine, mycophenolate mofetil and prednisone. Patients were followed for 6 months after the transplantation. Pharmacokinetic and pharmacodynamic studies were performed up to 20 weeks after the transplantation. In patients treated with a single dose of daclizumab, the blood concentrations of daclizumab declined to 1 micro g/mL at 43 +/- 7 days after the transplantation. In patients treated with two doses of daclizumab, the blood concentrations of daclizumab declined to 1 micro g/mL at 45 +/- 13 days after the second dose for a total of 59 +/- 13 days after the transplantation. Daclizumab levels of 1 micro g/mL or greater were associated with saturation of the IL-2Ralpha on the circulating lymphocytes. In the new era of effective maintenance immunosuppression, a limited dosing regimen of daclizumab may be desired, practical and economical.", "Patient entry is now complete in a prospective trial of anti-Tac, a murine IgG2a monoclonal antibody directed against the p55 chain of the human IL-2 receptor, for the prevention of renal allograft rejection. Recipients of primary cadaver allografts were randomized to receive either anti-Tac (20 mg q.d. x 10 days beginning POD 1) plus low-dose CsA (4 mg/kg/day), azathioprine (2 mg/kg/day), and prednisone (30 mg q.d.), or conventional triple therapy with CsA (8 mg/kg/day), azathioprine, and prednisone. Forty patients were entered in each group, with current followup from 6 to 26 months. The results show a significant reduction in early rejection episodes in the anti-Tac-treated patients. During the 10-day treatment, 5 of 40 anti-Tac patients had rejection episodes, compared with 21 of 40 control patients (P less than 0.001). Anti-Tac significantly delayed the time to the first rejection (12.5 +/- 6.3 vs. 7.6 +/- 6.7 days) (P less than 0.05). Despite these effects, there were no differences in either actual or actuarial graft or patient survival between the two groups. Pneumonia, primarily CMV, developed in 5 treated and 4 control patients. In patients with functioning grafts mean serum creatinine at 3 months was 1.8 +/- 0.7 in the anti-Tac group and 2.0 +/- 0.8 in the control group (P = NS); at 12 months the values were 2.3 +/- 1.5 and 1.8 +/- 0.5, respectively (P = NS). The peak expression of IL-2 receptors on circulating T-cells was significantly lower in anti-Tac patients (15.1 +/- 3.6%) than in controls (21.9 +/- 4.5%) (P less than 0.05). Seven of 10 patients tested to date developed antimouse immunoglobulin antibodies, with antiidiotype shown in 6. These antibodies do not preclude subsequent treatment with OKT3. Five patients in this and previous anti-Tac protocols have received OKT3 for acute rejection despite known pretreatment antimouse antibodies, with resolution of rejection in all cases.", "Basiliximab, a monoclonal CD25 antibody has proofed effective in reducing acute rejection episodes in adults in various immunosuppressive regimens. The effect of basiliximab in the pediatric population is controversial.\n In a 12-month, double-blind, placebo-controlled trial, renal transplant patients aged 1 to 18 years were randomized to basiliximab or placebo with cyclosporine microemulsion, mycophenolate mofetil, and corticosteroids. The intent-to-treat population comprised 192 patients (100 basiliximab and 92 placebo).\n The primary efficacy endpoint, time to first biopsy-proven acute rejection episode, or treatment failure by month 6, occurred in 16.7% of basiliximab-treated patients and 21.7% of placebo-treated patients (Kaplan-Meier estimates; hazard ratio 0.72, two-sided 90% confidence interval 0.416-1.26, n.s.). The rate and severity of subclinical rejections in protocol biopsies performed at 6 months posttransplant was higher in the basiliximab group (25.0%) than in the placebo group (11.7%). Patient and death-censored graft survival at 12 months was 97% and 99%, respectively, in the basiliximab cohort, and 100% and 99% among placebo-treated patients (n.s.). Renal function was similar in both treatment groups, and there were no significant between-treatment differences in the incidence of adverse events or infections.\n Addition of basiliximab induction to a regimen of cyclosporine microemulsion, mycophenolate mofetil, and steroids resulted in a numerically lower but not significant incidence of biopsy-proven acute rejection versus placebo and excellent graft and patient survival at 1 year in pediatric renal transplant recipients. Whether this numerical difference is a true therapeutic benefit in view of the higher rate and severity of subclinical rejections in the basiliximab group in the protocol biopsy will be investigated in a long-term follow-up study.", "nan" ]

[ "19538334", "8558397", "17461960", "9857596", "15857065", "9545899", "15536784", "9797055", "11966923", "19711612", "15085873" ]

[ "Mechanical non-surgical treatment of peri-implantitis: a double-blind randomized longitudinal clinical study. I: clinical results.", "The effect of an antiseptic mouthrinse on implant maintenance: plaque and peri-implant gingival tissues.", "Peri-implant maintenance of immediate function implants: a pilot study comparing hyaluronic acid and chlorhexidine.", "Clinical and microbiologic effects of chemical versus mechanical cleansing in professional supportive implant therapy.", "Amine fluoride/stannous fluoride and chlorhexidine mouthwashes as adjuncts to single-stage dental implants: a comparative study.", "Effects of subgingival chlorhexidine irrigation on peri-implant maintenance.", "Treatment of incipient peri-implant infections using topical minocycline microspheres versus topical chlorhexidine gel as an adjunct to mechanical debridement.", "Effectiveness of a sonic toothbrush in maintenance of dental implants. A prospective study.", "Relative effectiveness of powered and manual toothbrushes in elderly patients with implant-supported mandibular overdentures.", "The effect of a triclosan dentifrice on mucositis in subjects with dental implants: a six-month clinical study.", "Microbiological and clinical effects of chlorhexidine enclosed in fixtures of 3I-Titamed implants." ]

[ "Peri-implantitis is a frequent finding in patients with dental implants. The present study compared two non-surgical mechanical debridement methods of peri-implantitis.\n Thirty-seven subjects (mean age 61.5; S.D+/-12.4), with one implant each, demonstrating peri-implantitis were randomized, and those treated either with titanium hand-instruments or with an ultrasonic device were enrolled. Data were obtained before treatment, and at 1, 3, and 6 months. Parametric and non-parametric statistics were used.\n Thirty-one subjects completed the study. The mean bone loss at implants in both groups was 1.5 mm (SD +/-1.2 mm). No group differences for plaque or gingival indices were found at any time point. Baseline and 6-month mean probing pocket depths (PPD) at implants were 5.1 and 4.9 mm (p=0.30) in both groups. Plaque scores at treated implants decreased from 73% to 53% (p<0.01). Bleeding scores also decreased (p<0.01), with no group differences. No differences in the total bacterial counts were found over time. Higher total bacterial counts were found immediately after treatment (p<0.01) and at 1 week for ultrasonic-treated implants (p<0.05).\n No group differences were found in the treatment outcomes. While plaque and bleeding scores improved, no effects on PPD were identified.", "The purpose of this controlled double-blind, parallel, randomized clinical study was to determine the effect of antiseptic mouthrinse on parameters important to dental implant maintenance. Plaque, peri-implant gingivitis, gingival bleeding, probing depth, and attachment level were assessed over a 3-month test period. Twenty healthy adult patients each of whom had at least two dental implants, a modified gingival index > 1.5, and a modified Quigley-Hein plaque index score > 1.7 were enrolled into the study. After a thorough oral prophylaxis, patients were randomly assigned to either the antiseptic mouthrinse or a 5% hydroalcohol placebo mouthrinse group and instructed to rinse twice daily for 30 seconds with 20 ml of their assigned mouthrinse as an adjunct to their usual oral hygiene procedures. The baseline examination included plaque index, gingival index, bleeding index, probing depth measurement, and attachment level measurements. The plaque and gingival indices were rescored at 1, 2, and 3 months. Probing depths, attachment levels, and bleeding index were determined again at 3 months only. At the end of 3 months, the antiseptic mouthrinse group had statistically significant reductions in plaque index, gingival index, and bleeding index compared to the placebo group. There were no significant differences between groups in probing depth or attachment level. The results of this clinical study indicate that twice daily use of an antiseptic mouthrinse may provide benefits in the maintenance of dental implants.", "In implants, maintenance assumes an important role. The role of chlorhexidine (CHX) is well known in maintenance, while only limited evidence exists on the practical use of hyaluronic acid (HA). The objective of this study was to compare the health status of the peri-implant complex (hard and soft tissues surrounding the implant) during the healing period of immediate function implants, using HA or CHX gels in the patient's maintenance protocol. STUDY POPULATION AND METHODOLOGY: Thirty complete edentulous patients, with four immediate function Brånemark System implants placed in the mandible (total of 120 implants), were randomly assigned to two groups (HA and CHX) using only these two chemicals in their daily implant self-care. Both groups were followed up for 6 months, with clinical observations on the 10th day, 2 months, 4 months and 6 months post-surgically.\n During the course of the study, HA and CHX produced good results in maintaining a healthy peri-implant complex in immediate function implants for complete rehabilitations in the edentulous mandible. Statistically significant differences were found in favour of the HA group in the modified bleeding index on the second observation (P = 0.003). The difference was more marked in the axial implants placed in the fifth sextant (P = 0.05). Correlation coefficient between plaque and bleeding index revealed a potentially better result for CHX at 6 months.\n The findings point out the importance of a maintenance protocol in immediate function implants. Both chemicals are valid tools for implant maintenance. The authors suggest that it might be advantageous to administer HA in the first 2 months and CHX between 2 and 6 months.", "The aim of the present study was to compare the cleansing properties of mechanical supportive care for dental implants with the use of an etching gel. Sixteen patients underwent a 5-month clinical trial with monthly recalls. These patients, wearing maxillary complete dentures and mandibular overdentures supported by a bar device on 4 implants, were treated in a split-mouth study design. Test and control therapy were randomly assigned to left and right sides of the mandible. At the test side, 35% phosphoric etching gel (pH 1) was applied in the peri-implant sulcus. After 1 minute, the sulcus was thoroughly rinsed with a water spray for approximately 15 seconds per implants. Control therapy consisted of supra- and subgingival debridement using carbon fiber curettes and a rubber cup. Plaque, calculus, probing pocket depth, and modified Gingival Index were determined before each treatment. Microbiologic evaluation was performed at baseline, 1 month later, and 5 months later, just before and immediately after each treatment. Per treatment and per assessment, the mean scores of all clinical parameters were calculated for each patient. The number of colony-forming units was used as the primary efficacy variable in the analysis of microbiologic data. At baseline, no differences between test and control sites were observed for any of the clinical parameters. The mean Gingival Index and the mean probing pocket depth were reduced over the 5-month period. The mean reduction in Gingival Index at the test sites proved to be significantly larger at the control sites (P = .03). Both treatment modalities resulted in an instant reduction of the number of colony-forming units, where the reduction by chemical cleaning was larger (P < .05). This short-term study employing a high recall frequency indicates that local application of 35% phosphoric acid gel can be as effective as conventional mechanical supportive therapy.", "The growing popularity of non-submerged dental implants in recent years requires a greater emphasis on microbial plaque control. Chlorhexidine (CHX), the most commonly used mouthwash in implant surgery, is sometimes associated with tooth staining and alteration in taste perception. Amine fluoride/stannous fluoride (AmF/SnF2) mouthwash has been shown to have anti-infective properties; however, it has not been tested as an adjunct anti-infective means in non-submerged dental implants. The purpose of this trial was to compare AmF/SnF2 and CHX mouthwashes as adjuncts to single-stage dental implants.\n Thirty-three patients aged 34 to 79 (mean 54.30 +/- 8.69 SD) requiring dental implants were accepted into the study. Following comprehensive periodontal therapy patients received one to three non-submerged dental implants (maxilla: 17; mandible: 45; anterior: 3, posterior: 59). After surgery patients were given analgesics and antibiotics as well as 2,400 ml of coded mouthwash bottles previously randomized between the two above mentioned formulations. Clinical and radiographic parameters were recorded at baseline and 3 and 12 months post-surgery.\n Twelve-month survival rates were 100% and 92.9% for the AmF/SnF2 and CHX groups, respectively. Compliance was slightly higher in the AmF/SnF2 group (84.35% +/- 3.39% versus 78.15% +/- 4.59% SE) but statistically similar. There was no statistically significant difference between the AmF/SnF2 and CHX groups in staining index at 3 months (1.519 +/- 0.22 versus 1.457 +/- 0.24 SE) and patient subjective evaluation of the mouthwashes. Radiographic bone loss was 0.79 +/- 0.23 and 1 +/- 0.13 SE at 3 months and 1.06 +/- 0.13 and 1.27 +/- 0.25 at 12 months for the CHX and AmF/SnF2 groups, respectively; the difference was statistically insignificant (P = 0.388 and 0.504, respectively).\n Both CHX and AmF/SnF2 mouthwashes can be used post-surgically after one-stage implant surgery.", "To evaluate the effect of irrigation with 0.06% chlorhexidine (PerioGard) (CHX) using a powered oral irrigator (Water Pik) with a special subgingival irrigating tip (Pik Pocket Subgingival Tip) compared to rinsing with 0.12% chlorhexidine gluconate once daily.\n Following a prophylaxis, patients were randomly assigned to an irrigation or a rinse group. The following clinical parameters were measured at baseline and at the 3-month end of the study: Modified Gingival Index (MGI), Plaque Index (PI), Bleeding Index (BI), and Calculus Index (CI). Also, a Stain Index (SI) was measured at 3 months.\n Patients irrigating with diluted CHX showed a statistically significant reduction (P < 0.05) from their baseline in the MGI, PI, BI, and CI scores at 3 months. In the rinse group both MGI and BI showed statistically significant reduction from their baseline (P < 0.05) at 3 months. The rinse group showed a nonsignificant (P > 0.05) increase from baseline in CI and a nonsignificant decrease in PI. Intergroup comparisons showed that CHX irrigation produced statistically significantly greater reductions than CHX rinsing in the PI, MGI, and SI. The irrigation group also showed a greater reduction in BI and CI than the rinsing group but these differences were not statistically significant (P = 0.12). The results of this study suggest that use of diluted 0.06% CHX when used in a powered irrigator may be a valuable adjunct to oral health in patients with implants.", "This report presents the clinical results three months after application of minocycline microspheres as an adjunct to mechanical treatment of incipient peri-implant infections compared to adjunctive treatment employing 1% chlorhexidine gel application. Sixteen patients in the minocycline group and 14 in the chlorhexidine group completed the study. Each patient had one or more implants with probing depth > or = 4 mm combined with bleeding and/or exudate on probing and presence of putative pathogenic bacteria. At baseline, patients were randomly assigned to minocycline or chlorhexidine treatment. Follow-up examinations were carried out after 10, 30, 60 and 90 days. The combined mechanical/antimicrobial treatment for the chlorhexidine group did not result in any reduction in probing depth and only limited reduction of bleeding scores. The adjunctive use of minocycline microspheres, on the other hand, resulted in improvements in both probing depths and bleeding scores. For the deepest sites of the treated implants, mean probing depth was reduced from 5.0 mm to 4.1 mm. The reductions in bleeding scores, although greater than for the chlorhexidine group, were modest. Thus, the question as to what extent the combined mechanical/minocycline treatment could be considered adequate for the treated lesions remains to be answered. The present short-term findings, however, encourage further studies with longer observation intervals on adjunctive use of minocycline microspheres in the treatment of periimplant lesions.", "This study assessed the efficacy of a sonic and a manual toothbrush in reducing plaque and gingivitis around dental implants. Subjects were randomly assigned to either sonic (n = 16) or manual (n = 15) study groups. Groups were balanced according to baseline levels of plaque and gingivitis. The plaque (PI), gingival (GI), and bleeding (BI) indices as well as probing depths were determined at baseline, and at 4, 8, 12, and 24 week follow-up visits. Mean scores per person were calculated for each clinical parameter. Oral hygiene habits, compliance and acceptance were also evaluated over the study period. Within group comparisons from baseline throughout the study, as well as between group comparisons (i.e., sonic versus manual), were determined. Overall, plaque, gingival, and bleeding indices in both groups were lower at each follow-up visit when compared to the baseline. Within group comparisons demonstrated that both the sonic toothbrush subjects and the manual toothbrush subjects had significantly lower PI, GI, and BI scores at each post-baseline visit (4, 8, 12, and 24 weeks) than at baseline (p<0.005). In addition, the sonic toothbrush subjects also had significantly lower probing depths at each post-baseline visit than at baseline (p < 0.005). Between group comparisons demonstrated that the sonic toothbrush subjects over time had significantly lower PI and BI scores around dental implants than the manual toothbrush subjects (Repeated measures MANOVA; PI, p = 0.01; BI, p = 0.017). The sonic toothbrush subjects had lower GI scores and reduced probing depths over time when compared to manual toothbrush subjects but these scores were not statistically significant (GI; probing depth, p > 0.05). No implant problems (e.g., loose screws) were attributable to the sonic toothbrush. Relevant to oral hygiene habits, subjects in both groups demonstrated a high level of compliance with their assigned toothbrush. Overall, the results of this study demonstrated that sonic toothbrushing significantly reduced plaque, gingival inflammation and bleeding, and probing pocket depths around implants over the 6-month trial period. It is concluded that sonic brushing is an effective means of dental implant maintenance.", "The aim of this study was to compare the clinical effectiveness of a powered toothbrush (Braun Oral-B Plaque Remover 3-D) and a manual soft toothbrush (Oral-B Squish-grip brush) for the control of supragingival plaque and soft tissue inflammation around implants supporting mandibular overdentures.\n The study sample involved 40 edentulous subjects, aged 55-80 years, having 2 unsplinted mandibular implants supporting a complete removable overdenture opposed by a maxillary complete denture. In this single-blinded, randomised, cross-over clinical trial, two 6-week experimental phases were separated by a 2-week wash-out period. 2 weeks prior to each experimental phase (pre-entry visits), implant abutments were polished to remove all plaque and a standardised instruction in the use of the toothbrush was given. Modified plaque and bleeding indices were recorded at the start and end of each experimental period. Mean index scores at each phase were analysed using paired t-test, and the mean number of sites showing a change in plaque or mucositis were compared using the Mann-Whitney U-test. Combined data from 2 different implant systems were considered after controlling for implant type.\n Only minor changes in plaque and bleeding scores were observed following the two test periods. There were no statistically significant differences between the manual and powered toothbrushes.\n Manual and powered brushes were found to be of comparable efficacy with regard to improvement in peri-implant bleeding and plaque indices.", "The objective of the present clinical study was to assess the effect of the use of a dentifrice containing triclosan on peri-implant mucositis in subjects that had been restored with dental implants.\n The trial was designed as a double-blind, randomized, two-treatment, parallel-group clinical study. Sixty male and female subjects, aged 30-70 years, were recruited. All subjects had lost teeth due to periodontal disease, and had been restored with a minimum of two implants at least one year prior to the start of the trial. Subjects were randomly assigned to two treatment groups. The subjects in the test group (Test) brushed their teeth and implant-supported restorations with a dentifrice containing triclosan, while the control subjects brushed with a sodium fluoride dentifrice. Only subjects with a minimum of one implant site showing clinical signs of peri-implant mucositis, i.e., bleeding after probing, were enrolled in the study. Clinical examinations were performed at baseline, and after three and six months. The following parameters were scored: Probing pocket depth (PPD), bleeding on probing (BoP), and plaque. The change from baseline within each treatment group at three months and six months was evaluated for all parameters using ANOVA and ANCOVA.\n Subjects with peri-implant mucositis who used a dentifrice containing 0.3% triclosan, as an adjunct to mechanical tooth brushing, exhibited significantly fewer clinical signs of inflammation than subjects who used a regular fluoride dentifrice at six months. The BoP scores were reduced from 53.8% to 29.1% in the Test group, whereas in the same interval there was an increase from 52.3% to 58.8% in the Control group. Furthermore, the individual mean PPD, as well as the frequency of sites with 5 mm and > or = 6 mm deep pockets, were reduced significantly more in the Test than in the Control group.\n The regular use of a dentifrice containing triclosan may reduce the clinical signs of inflammation in the mucosa adjacent to dental implants.", "This double-blind study used a split-mouth design to investigate the microbiological and clinical effects of 0.2% chlorhexidine enclosed in fixtures. Twelve patients had 46 fixtures implanted. At second-stage surgery, a microbiological sample (baseline sample) of the inner parts of the fixtures was taken. Then, a 0.2% chlorhexidine solution was applied into the inner space of 23 fixtures (test group), and in 23 fixtures saline was applied (control group). Abutments were installed and gingival index, plaque index and crevicular fluid flow were monitored weekly. After 6 weeks, a second microbiological sample of the inner part of the fixtures was taken. At baseline, viable bacteria were detected within 46% of the fixtures. After weeks, bacteria were found in 87% of the fixtures. The numbers of bacteria in the control group were significantly higher than those in the test group. The results indicate that, after first-stage surgery, contamination of the inner spaces of the fixtures is commonplace. Application of a 0.2% chlorhexidine solution at second-stage surgery inhibits growth or acquisition of bacteria in the fixtures. In both test and control groups, the crevicular fluid flow as well as the gingival index decreased during the experimental period. At 4, 5, and 6 weeks after chlorhexidine application, these values in the test group appeared lower, but did not attain statistical significance." ]

[ "11381380", "8445463", "3858479", "2681610", "11844036", "1814964", "11826641" ]

[ "Efficacy of temporomandibular joint arthrocentesis with and without injection of sodium hyaluronate in treatment of internal derangements.", "Use of sodium hyaluronate in treating temporomandibular joint disorders: a randomized, double-blind, placebo-controlled clinical trial.", "The short-term effect of intra-articular injections of sodium hyaluronate and corticosteroid on temporomandibular joint pain and dysfunction.", "Preliminary studies on the use of a viscoelastic solution in arthroscopic surgery of the temporomandibular joint.", "The efficacy of intra-articular sodium hyaluronate in patients with reducing displaced disc of the temporomandibular joint.", "Short-term effects of intra-articular sodium hyaluronate, glucocorticoid, and saline injections on rheumatoid arthritis of the temporomandibular joint.", "[Randomized controlled trial of sodium hyaluronate for degenerative disorders of the temporomandibular joint]." ]

[ "This study was designed to investigate the efficacy of arthrocentesis with and without injection of sodium hyaluronate (SH) into the upper joint space in the treatment of temporomandibular joint (TMJ) internal derangements.\n Forty-one TMJs in 5 males and 26 females aged 14 to 53 years comprised the study material. The patients' complaints were limited mouth opening, TMJ pain and tenderness, and joint noises during function. Patients were randomly divided into 2 groups in which only arthrocentesis was performed in 1 group and arthrocentesis plus intra-articular injection of sodium hyaluronate was performed in the other group. Both groups contained patients with disc displacement with reduction and with closed lock. Clinical evaluation of the patients was done before the procedure, immediately after the procedure, on postoperative day 1, and at 1, 2, 3, 4, 5, 6, 9, 12, 18, and 24 months postoperatively. Intensity of TMJ pain, jaw function, and clicking sounds in the TMJ were assessed using visual analog scales. Maximal mouth opening and lateral jaw movements also were recorded at each follow-up visit.\n Both techniques increased maximal mouth opening, lateral movements, and function, while reducing TMJ pain and noise.\n Although patients benefitted from both techniques, arthrocentesis with injection of SH seemed to be superior to arthrocentesis alone.\n Copyright 2001 American Association of Oral and Maxillofacial Surgeons.", "This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporomandibular joint (TMJ) disorders. One hundred twenty-one patients were studied at three test sites using a randomized, double-blind, placebo-controlled experimental design. Patients were selected on the basis of 1) confirmed diagnosis of either degenerative joint disease (DJD), reducing displaced disc (DDR), or nonreducing displaced disc (DDN); 2) nonresponsiveness to nonsurgical therapies; and 3) severe dysfunction as established by the Helkimo indices (HI), visual analog scales (VASs), and physical measurements of joint movement and joint noise (arthrophonometry [APM]). Subjects received a unilateral upper joint space injection of either 1) 1% sodium hyaluronate in physiologic saline (MedChem Products, Woburn, MA) or 2) USP physiologic saline. Clinical evaluations were performed using HI, VAS, and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection. Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval. For DJD, no difference in outcome was seen between treatment groups. For DDN, significant between-group differences were seen through 1 month; however, beyond this time point, the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy. For DDR, statistically significant within-group and between-group improvement in all three measures (HI, VAS, APM) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period. At the month-2 and month-3 examination intervals, twice as many patients treated with hyaluronate (90%) showed improvement compared to patients given placebo. Further, only 3% of patients with DDR who were treated with hyaluronate relapsed compared with 31% of patients with DDR given placebo.", "The short-term effect of intra-articular injections of sodium hyaluronate and a corticosteroid (betamethasone) was compared in a sample of 33 patients who had pain and tenderness to palpation in the temporomandibular joint of at least six months duration that had not responded to previous conservative treatment. The two drugs were randomly allocated to the patients. A volume of 0.5 ml of the drug was injected twice into the superior joint compartment of the TMJ with a two-week interval between injections. The effect on subjective symptoms, clinical signs, and bite force was assessed. Both drugs reduced the symptoms and signs significantly, and no statistically significant difference in effect could be found between drugs in this regard. The results indicate that the difference between the drugs in terms of short-term therapeutic effects is small, and that sodium hyaluronate could be used as an alternative to corticosteroid for patients who have signs of TMJ inflammation, especially for those who have symptomatic osteoarthrosis.", "Arthroscopic surgery of the temporomandibular joint includes the potential for iatrogenic damage of intracapsular structures during introduction of instruments and manipulation of the tissues. A modification of an elastoviscous solution of crosslinked sodium hyaluronate, called hylan fluid, was used for irrigation during surgery in 55 temporomandibular joints. Forty-nine of the joints were monitored postoperatively in a study to measure safety and efficacy of the material during the arthroscopic procedure. The hylan fluid was found to be as safe as the standard irrigating fluid. The hylan fluid also significantly protected the joint surfaces and facilitated the surgical procedure.", "In this clinical trial, we examined the efficacy of intra-articular hyaluronic acid (HA) treatment in 38 patients with reducing displaced disc of the temporomandibular joint (TMJ). Subjects received two unilateral upper space injections of HA or physiological saline solution with 1 week apart. Efficacy was based on the following measurements: pain and sound intensity of the joint measured by visual analogue scale (VAS), modified Helkimo's clinical dysfunction index and the intensity of joint vibration during opening and closing the mouth measured by accelerometers. These measurements were performed before the first injection and 1 and 6 months after the last injection. In the treatment group (n=19), all measurements improved significantly at month 1 and at month 6 compared with the baseline (P < 0.01). The same measurements, in the placebo group (n=19), did not show any change, except for the pain intensity which improved at month 1 and month 6 (P < 0.05). The change in baseline measurements of all of the efficacy criteria at month 1 and at month 6 in the treatment group was significantly better compared with the change obtained with placebo at the same time intervals. This study demonstrates that intra-articular sodium hyaluronate (Orthovisc) injection into the TMJ is an effective treatment for a reducing displaced disc.", "The short-term effect (4 weeks) of intra-articular injections of sodium hyaluronate, glucocorticoid, and saline was studied in three groups comprising 41 patients with rheumatoid arthritis of the temporomandibular joint. Sodium hyaluronate and glucocorticoid treatments had a significant positive effect according to the patients' subjective evaluation. A comprehensive clinical dysfunction score was reduced significantly in all groups, while the number of tender muscle regions was significantly reduced and the maximum voluntary mouth opening significantly increased in the glucocorticoid and sodium hyaluronate groups only.", "To assess the effect of sodium hyaluronate (HA) for degenerative disorders of the temporomandibular joint (TMJ).\n A prospective randomized controlled clinical trial was conducted. The experimental group received injections in the upper compartments of the involved TMJs with 1% HA 6 mg, whereas the control group received prednisolone (PS) 12.5 mg once a week. Three to four injections were as one course. Before and one week after the treatment courses, clinical symptoms, amount of interleukin-6 (IL-6) and total protein of synovial fluid were measured and compared.\n Sixty-seven patients were included and 4 out of them were dropped out. There were 12 males and 51 females, among them, 14 cases with synovitis, 21 with anterior disc displacement without reduction and 28 with osteoarthritis of the TMJ. Thirty-five patients allocated in HA group and 28 in PS group. Both drugs could relieve the clinical symptoms of TMJ degenerative disorders. In HA group, marked improvement rate was 51.43% and failure rate was 2.86%, whereas marked improvement rate 39.29% and failure rate 17.86% in PS group. The declined levels of IL-6 in synovial fluid was notably greater in HA group than those in PS group.\n Intra-articular injection of HA is effective and safe to treat TMJ degenerative disorders with mild adverse reactions, better in terms of effective rate and declined level of IL-6 than PS." ]

[ "12745558", "10485722", "9197872" ]

[ "A randomised, double-blind placebo-controlled trial of ascorbic acid supplementation for the prevention of preterm labour.", "Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.", "Antioxidants in the treatment of severe pre-eclampsia: an explanatory randomised controlled trial." ]

[ "In a previous study from this institution, patients at high risk for preterm labour were screened for the presence of bacterial vaginosis (BV). When BV was present, they were randomised to receive either treatment (metronidazole) or placebo (vitamin C). There were significantly more patients with preterm labour in the metronidazole group. The aim of this double-blind randomised placebo-controlled trial study was to determine whether vitamin C could indeed reduce the recurrence risk of preterm labour. Patients with a history of preterm labour in a preceding pregnancy were randomised to receive 250 mg vitamin C or a matching placebo twice daily until 34 weeks' gestation. They attended a dedicated premature labour clinic. Significantly more women delivered before term in the group that received vitamin C, but there was no difference in the outcome of the babies between the two groups. Supplementation with vitamin C did not prevent premature labour.", "Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia.\n 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study.\n Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002).\n Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.", "To determine whether antioxidant therapy alters the disease process in severe early onset pre-eclampsia, in support of the hypothesis that increased lipid peroxides and reactive oxygen species production-play an important role in the pathogenesis of the disease.\n Randomised, double-blind, placebo controlled trial.\n Two tertiary care, referral hospitals in Johannesburg, South Africa.\n Women with severe pre-eclampsia diagnosed between 24 and 32 weeks of gestation.\n Combined antioxidant treatment with vitamin E (800 IU/day), vitamin C (1000 mg/day), and allopurinol (200 mg/day).\n Primary outcomes: 1. prolongation of pregnancy and 2, biochemical assessment of lipid peroxides and antioxidants. Secondary outcomes: data on maternal complications, side effects of treatment, infant outcomes and regular assessment of haematologic and renal parameters.\n The proportion of women delivered within 14 days in the antioxidant group was 52% (14/27) compared with 76% (22/29) in the placebo group (relative risk 0.68, 95% confidence interval 0.45-1.04). One woman in each group had eclampsia. Eleven women (42%) in the antioxidant and 16 (59%) in the placebo group required two antihypertensives for blood pressure control. Trial medications were well tolerated with few side effects. Lipid peroxide levels were not significantly altered in the antioxidant and placebo groups. Serum uric acid levels decreased and vitamin E levels increased significantly.\n The results of this explanatory randomised trial do not encourage the routine use of antioxidants against pre-eclampsia. However, further research with modified strategies such as earlier initiation of therapy or different combinations seem worthwhile." ]

[ "10971602", "11552002", "14610140", "11789240" ]

[ "Randomized controlled trial of brain-derived neurotrophic factor in Guillain-Barré syndrome: a pilot study.", "CSF filtration is an effective treatment of Guillain-Barré syndrome: a randomized clinical trial.", "A randomized controlled trial of recombinant interferon-beta 1a in Guillain-Barré syndrome.", "[Effect of Tripterygium polyglycoside on interleukin-6 in patients with Guillain-Barre syndrome]." ]

[ "Brain-derived neurotrophic factor (BDNF) has the theoretical potential to protect neurones from axonal degeneration. The objective of this study was to discover whether brain-derived neurotrophic factor is safe in Guillain-Barré syndrome, and to make preliminary observations of its efficacy. This was a parallel group randomized controlled trial of subcutaneous brain-derived neurotrophic factor 25 microg/kg daily compared with placebo for up to 24 weeks or until patients could walk without aid. Six patients received brain-derived neurotrophic factor, of whom three had serious adverse events including one death. Four patients received placebo, of whom two had serious adverse events including one death. The rate and extent of recovery were similar in the two groups. This pilot study did not detect any serious adverse events attributed to brain-derived neurotrophic factor treatment.", "To compare CSF filtration (CSFF) and plasma exchange (PE) in the treatment of patients with Guillain-Barré syndrome (GBS).\n In a prospective controlled clinical trial, 37 patients with acute GBS were randomized to receive either CSFF or PE. Inclusion criteria were fulfillment of National Institute of Neurological and Communicative Disorders and Stroke criteria and disability to walk >5 m unassisted.\n With similar baseline features in both groups (initial disability grades on the six-point grading scale of the GBS Study Group) the primary outcome variable (improvement within 28 days after randomization) was almost identical (test for equivalence p = 0.0014), the mean grade values being 0.82 in the CSFF group and 0.80 in the PE group. After 56 days, 56% (9 of 16 patients) of the CSFF group and 37% (7 of 19 patients) of the PE group had reached grade 2 (i.e., ability of unassisted walking >5 m). After 6 months, the probability to reach grade 2 was about 80% in both groups. In the CSFF group, transient pleocytosis occurred without apparent clinical complications. Clinically relevant complications were higher in the PE-treated group.\n Although the number of patients was small, the authors found that the treatment of GBS with CSFF is at least as effective as with PE. CSFF might work by removing from the CSF inflammatory mediators, autoantibodies, or other factors.", "The authors recruited 19 nonambulant patients with Guillain-Barré syndrome into a pilot, double-blind, randomized, placebo-controlled safety trial of interferon beta 1a (IFN[beta]-1a) (Rebif). Participants received IFN[beta]-1a or placebo subcutaneously three times weekly, 22 microg for the first week and then 44 microg for up to 24 weeks, in addition to IV immunoglobulin (IVIg). IFN[beta] did not have any unexpected interaction with IVIg and there was no significant difference in rate of improvement.", "To study the action of interleukin-6(IL-6) in pathogenesis and effect of patients with Guillain-Barre syndrome (GBS).\n Forty-three patients of GBS were selected according to Asbury's standard and divided into two groups on layer randomize principle, they were treated with adrenal corticosteroid and Tripterygium polyglycoside (TP) respectively. Serum and cerebrospinal fluid (CSF) content of IL-6 were measured by double antibody sandwich ELISA method.\n (1) The serum and CSF content of IL-6 in GBS group was higher than those in the normal control group significantly; (2) There was positive correlation between CSF IL-6 and clinical severity (P < 0.01) before treatment; (3) After treatment the clinical symptoms were improved in both groups, but the TP treated group showed better effect than the control group in improving symptoms and lowering serum IL-6 level (P < 0.05).\n CSF level of IL-6 could be taken as one of the criteria for severity evaluation of patient's condition. TP is superior in suppressing abnormal immune reaction to adrenal corticosteroid in GBS patients." ]

[ "17234558", "2563951", "12492193", "16573804", "2857633", "2899536", "15679762", "2906476", "20049950", "20878425", "2337059", "11856080", "11515850", "11856079", "12094857", "2906888", "15133864", "2567266", "15854171", "9726382", "17241860", "16279903", "18080055", "1863024", "15507864", "8338086", "19491859", "1980911", "16984503", "8563868", "15017515", "18832520", "3317057", "15606398", "19766640", "2684804" ]

[ "Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of remission of mild to moderately active ulcerative colitis.", "Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial.", "Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute mild-to-moderate ulcerative colitis.", "Comparison of the efficacy and safety of Eudragit-L-coated mesalazine tablets with ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis.", "[Successful acute treatment of chronic inflammatory intestinal diseases with oral 5-aminosalicylic acid].", "Comparison of delayed release 5 aminosalicylic acid (mesalazine) and sulphasalazine in the treatment of mild to moderate ulcerative colitis relapse.", "A double-blind dose-escalating trial comparing novel mesalazine pellets with mesalazine tablets in active ulcerative colitis.", "Double-blind comparison of olsalazine and sulphasalazine in active ulcerative colitis.", "Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study.", "Clinical trial: Effects of an oral preparation of mesalazine at 4 g/day on moderately active ulcerative colitis. A phase III parallel-dosing study.", "Double-blind placebo-controlled study of olsalazine in the treatment of ulcerative colitis.", "A double-blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis.", "Mesalazine 4 g daily given as prolonged-release granules twice daily and four times daily is at least as effective as prolonged-release tablets four times daily in patients with ulcerative colitis.", "A double-blind comparison of balsalazide, 6.75 g daily, and sulfasalazine, 3 g daily, in patients with newly diagnosed or relapsed active ulcerative colitis.", "A randomized, double blind, dose-response comparison of balsalazide (6.75 g), balsalazide (2.25 g), and mesalamine (2.4 g) in the treatment of active, mild-to-moderate ulcerative colitis.", "Prospective, randomized, double-blind comparison of benzalazine and sulfasalazine in the treatment of active ulcerative colitis.", "Different therapy for different types of ulcerative colitis in China.", "Olsalazine or sulphasalazine in first attacks of ulcerative colitis? A double blind study.", "Multicentre randomized-controlled clinical trial of Ipocol, a new enteric-coated form of mesalazine, in comparison with Asacol in the treatment of ulcerative colitis.", "Olsalazine versus mesalazine in the treatment of mild to moderate ulcerative colitis.", "Once-daily, high-concentration MMX mesalamine in active ulcerative colitis.", "Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial.", "Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared to 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial.", "Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study.", "Low-dose balsalazide plus a high-potency probiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis.", "Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. Pentasa Study Group.", "Safety and efficacy of a new 3.3 g b.i.d. tablet formulation in patients with mild-to-moderately-active ulcerative colitis: a multicenter, randomized, double-blind, placebo-controlled study.", "Therapeutic effectiveness and tolerance of 5-aminosalicylic acid in short term treatment of patients with ulcerative colitis at a low or medium phase of activity.", "Once daily MMX mesalazine for the treatment of mild-to-moderate ulcerative colitis: a phase II, dose-ranging study.", "Double-blind comparative study of sulfasalazine and controlled-release mesalazine tablets in the treatment of active ulcerative colitis.", "The optimal dose of 5-aminosalicylic acid in active ulcerative colitis: a dose-finding study with newly developed mesalamine.", "Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial.", "Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.", "Mesalazine (5-aminosalicylic acid) micropellets show similar efficacy and tolerability to mesalazine tablets in patients with ulcerative colitis--results from a randomized-controlled trial.", "Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis.", "Olsalazine versus placebo in the treatment of mild to moderate ulcerative colitis: a randomised double blind trial." ]

[ "SPD476 (MMX mesalamine), a novel, once-daily mesalamine formulation, uses MMX Multi Matrix System (MMX) technology to delay and extend delivery of active drug throughout the colon. We performed a randomized, double-blind, parallel-group, placebo-controlled, multicenter phase III study in patients with mild to moderately active ulcerative colitis.\n Two hundred eighty patients with mild to moderately active ulcerative colitis received MMX mesalamine 2.4 g/day given twice daily (n = 93), 4.8 g/day given once daily (n = 94), or placebo (n = 93) for 8 weeks. The primary end point was the percentage of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index score of < or =1, with a score of 0 for rectal bleeding and stool frequency, and at least a 1-point reduction in sigmoidoscopy score) at week 8. Patients with mucosal friability were not considered to have achieved this end point.\n Clinical and endoscopic remission at week 8 was achieved by 34.1% and 29.2% of patients receiving MMX mesalamine 2.4 g/day given twice daily and MMX mesalamine 4.8 g/day given once daily, respectively, versus 12.9% receiving placebo (P < .01). MMX mesalamine was generally well-tolerated.\n MMX mesalamine given once or twice daily is well-tolerated and, compared with placebo, demonstrated efficacy for the induction of clinical and endoscopic remission in mild to moderately active ulcerative colitis.", "To assess the safety and efficacy of a preparation of mesalazine (5-aminosalicylic acid) coated with a pH dependent resin (Eudragit L) as compared with sulphasalazine in patients with active mild to moderate ulcerative colitis.\n Eight week randomised double blind parallel group study.\n Forty six gastroenterology outpatient clinics in seven countries.\n Two hundred and twenty patients aged 18-70 who met the following criteria: clinical activity index greater than or equal to 6 and endoscopic index greater than or equal to 4; no concomitant treatment for ulcerative colitis; no hypersensitivity to salicylates or sulphonamides. Of the 164 patients eligible for efficacy analysis, 87 received the coated preparation of mesalazine and 77 sulphasalazine. Most of the remaining patients (28 in each group) were ineligible for the efficacy analysis because of treatment with steroid enemas. All pretrial characteristics were comparable in the two treatment groups.\n Coated mesalazine (Mesasal) 1.5 g daily or sulphasalazine 3.0 g daily for eight weeks. Compliance monitored by pill counts.\n Clinical and endoscopic remission.\n Clinical activity measured by daily diary cards, assessment by investigators, and laboratory findings. Endoscopic evaluation at week 8. After four weeks 50 of 70 patients (71%) taking coated mesalazine and 38 of 58 (66%) taking sulphasalazine had achieved remission of their disease by eight weeks remission rates were 74% (37/50 patients) and 81% (35/43) in the two treatment groups respectively. Endoscopic remission at eight weeks was recorded in 20 of 41 patients (49%) taking coated mesalazine and 18 of 38 (47%) taking sulphasalazine. There was a higher incidence of adverse events among patients taking sulphasalazine (25/105; 24%) than among those taking coated mesalazine (16/115; 14%).\n Mesalazine coated with Eudragit L is a safe, logical alternative to sulphasalazine.", "Balsalazide is a novel azo-bonded 5-aminosalicylic acid treatment for mild-to-moderate ulcerative colitis. The study objective was to compare symptomatic remission rates with balsalazide and mesalamine while controlling for extent of disease and time since diagnosis in patients with active, mild-to-moderate ulcerative colitis.\n A total of 173 patients with sigmoidoscopically verified ulcerative colitis were randomized to 8 wk of double-blind treatment with balsalazide 6.75 g/day or mesalamine 2.4 g/day. Both treatments provided 2.4 g/day of oral 5-aminosalicylic acid. Patients maintained symptom diaries throughout the treatment period.\n Overall, 46% of balsalazide- and 44% of mesalamine-treated patients achieved symptomatic remission. Higher response rates were noted in newly diagnosed patients with < or = 40 cm of disease (68% vs 61%) than in recently relapsed patients with >40 cm of disease (36% vs 25%). The median time to symptomatic remission was 12 days shorter with balsalazide (25 days) than with mesalamine (37 days). Significantly more balsalazide patients showed sigmoidoscopic (p = 0.002), stool frequency (p = 0.006), rectal bleeding (p = 0.006), and physician's global assessment score (p = 0.013) improvement by 14 days than did mesalamine patients. Similar proportions of patients reported adverse events (54% vs 64%), which were most commonly related to the gastrointestinal and central and peripheral nervous systems.\n Balsalazide is an effective and safe treatment for mild-to-moderate ulcerative colitis. Improvement of symptoms occurs considerably earlier with balsalazide than with mesalamine.", "There are no comparative studies of coated mesalazine.\n To compare the efficacy and tolerability of Eudragit-L- and ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis.\n A double-blind, double-dummy, randomized parallel group trial was performed across 18 centres in Australia, and 20 in Eastern Europe. Patients were treated with 3 g mesalazine for 8 weeks with the primary efficacy end point being clinical remission.\n Of 215 patients, 69% achieved clinical remission in both treatment groups (P < 0.001; chi-square test) with no differences in frequency of adverse events. In the Australian cohort (n = 63), the Eudragit-L group had a higher remission rate (73% vs. 36%) and responded 13 days faster, compared with those in the European group (67% vs. 84%, and 2 days respectively). No clear reasons for differences in treatment responses were identified.\n Eudragit-L and ethylcellulose-coated mesalazine tablets are well tolerated and equally effective in achieving remission in mild-moderately active ulcerative colitis over 8 weeks.", "The effectiveness of oral 5-aminosalicylic acid (0.5 g t.i.d.) and of salazosulfapyridine (1.0 g t.i.d.) was compared in a randomized controlled study in two groups with 30 patients each with ulcerative colitis and with Crohn's disease. Persistent complaints within the first 5 days were treated with additional methyl-prednisolone (40 mg/d initially). After treatment for 8 weeks patients with ulcerative colitis showed morphologic remissions in 60% of the 5-aminosalicylic acid group and in 53% of the salazosulfapyridine group. Clinical improvement was achieved in 86% in both groups. Clinical improvement in Crohn's disease was seen in 87% of patients of the 5-aminosalicylic acid group and in 80% of the salazosulfapyridine group. This was evidenced by the significant fall (P = 0,0001) of the mean activity index. Additional steroid medication was nearly equal in both treatment groups. There were no side effects during treatment with 5-aminosalicylic acid. In contrast, salazosulfapyridine had to be withdrawn in four patients due to signs of intolerance. 5-Aminosalicylic acid can thus be considered a valuable alternative to conventional treatment on the basis of equal effectiveness as salazosulfapyridine and lack of undesirable side effects.", "Oral formulations of 5-aminosalicylic acid (mesalazine) appear less toxic than sulphasalazine. We have therefore compared sulphasalazine, low dose mesalazine and high dose mesalazine in the treatment of mild to moderate relapse of ulcerative colitis. Sixty one patients (32 men, aged 20-78 years) were randomly allocated to sulphasalazine 2 g daily, mesalazine 800 mg daily, or mesalazine 2.4 g daily in a double blind, double dummy, four week trial. Groups were comparable for age, sex, extent of disease, and pretrial sulphasalazine intake. Four patients were unable to complete the study because of treatment failure (two taking sulphasalazine and two high dose mesalazine). A further two patients taking sulphasalazine developed side effects necessitating withdrawal. Within treatment comparisons revealed significant improvement of: sigmoidoscopic grade in the sulphasalazine group; rectal bleeding, sigmoidoscopic and histological grade in the low dose mesalazine group; stool frequency, rectal bleeding and sigmoidoscopic grade in the high dose mesalazine group. Greater improvement in rectal bleeding (p less than 0.05) and sigmoidoscopic appearances (p less than 0.05) occurred in patients taking high dose mesalazine than in those taking sulphasalazine. In two patients taking high dose mesalazine minor rises of plasma creatinine concentrations occurred, suggesting the need to monitor renal function.", "Mesalazine as the treatment standard for ulcerative colitis can be applied in different galenical preparations.\n A novel formulation of mesalazine pellets with delayed and prolonged release characteristics was compared with conventional Eudragit L-coated tablets. Furthermore, the effect of mesalazine dose escalation on nonresponders was evaluated in both treatment groups.\n A total of 233 patients with mild to moderately active ulcerative colitis were randomized to receive either mesalazine (1.5 g/day in three doses) as pellets (n = 115) or tablets (n = 118) for 8 weeks. At insufficient response, the dose was increased to 3.0 g.\n The clinical remission rate (clinical activity index < or = 4) for pellets was 67% vs. 68% for tablets which statistically proved to be not inferior (significance level alpha = 2.5%). In patients without dose increase, the remission rate was 47% (pellets) vs. 42% (tablets). Endoscopic improvement was observed in 80% (pellets) vs. 83% (tablets), and histological improvement in 48% (pellets) vs. 52% (tablets) of patients.\n Mesalazine pellets are as effective as tablets in the treatment of mild to moderately active ulcerative colitis. Dose escalation to 3.0 g/day is a valid option for nonresponders to a starting dose of 1.5 g/day.", "Fifty-six patients with ulcerative colitis of mild to moderate severity were entered into a randomized, double-dummy comparison of sulphasalazine, 3 g/day, with olsalazine, 3 g/day. Patients were assessed clinically, and by sigmoidoscopy and biopsy, on entry and at 5 weeks. Both agents produced a similar reduction in stool frequency and in the passage of blood and mucus. Improvements in sigmoidoscopic and histological appearances of the rectal mucosa were observed to a similar extent in both groups of patients. Two patients treated with olsalazine were withdrawn because of increased diarrhoea attributable to the medication. Two patients given sulphasalazine for the first time developed a skin rash. Other side-effects seen during the trial were mild. In this small short-term study, oral olsalazine appeared to be as effective as sulphasalazine in the treatment of mild to moderate ulcerative colitis.", "Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC.\n In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI).\n In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles.\n Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288).", "Oral mesalazine formulations are effective in the treatment of active ulcerative colitis (UC). It is not clear what induction dose of mesalazine is optimal for treating patients with active UC. We aimed to evaluate the efficacy and safety of 4 versus 2.25 g/day for selected patients with active UC.\n A multicenter, randomized, double-blind, parallel-group clinical study in 39 Japanese medical institutions. A total of 123 patients with moderately active UC received 4 g/day (two divided doses) versus 2.25 g/day (three divided doses) for 8 weeks. Primary endpoint was the ulcerative colitis-disease activity index (UC-DAI) score before and after 8 weeks of treatment. The improvement of each individual UC-DAI variable, remission, and efficacy rates were secondary endpoints. Safety was determined by laboratory data, vital signs, subjective symptoms, and objective findings.\n Patients receiving 4 g/day achieved a change in UC-DAI score significantly superior to those receiving 2.25 g/day [-3.0 (95% confidence intervals (CI) -3.8 to -2.3) vs. -0.8 (95% CI -1.8 to 0.1), respectively]. There were significant differences in all UC-DAI variables between the groups. Remission rates were 22.0% (4 g/day) and 15.3% (2.25 g/day). The efficacy rate was significantly better with 4 versus 2.25 g/day [76.3 vs. 45.8%, respectively (95% CI 13.8-47.2); P = 0.001]. No difference was seen in adverse events or adverse drug reactions.\n A dose of 4 g/day was significantly superior to 2.25 g/day in terms of UC-DAI score for patients with moderately active UC. Safety profiles were similar for both doses.", "Olsalazine is a compound consisting of two 5-amino salicylate (5-ASA) molecules linked by an azo bond, which, administered orally, is split by colonic bacteria to liberate 5-ASA. It lacks the sulfapyridine moiety found in sulfasalazine. Using a specific protocol, we conducted a randomized, double-blind, placebo-controlled trial of olsalazine in patients with symptomatic ulcerative colitis. Inclusion criteria included mild to moderate disease with involvement of more than 15 cm of colon, visible blood in stools, and the discontinuation of all other medications prior to and during the study. Patients were given oral olsalazine 3.0 g/day or placebo for 4 wk. Patients were evaluated clinically, by laboratory analysis and by colonoscopic evaluation, at entry and at 4 wk. Additional clinical and laboratory evaluations were performed at 2 wk. Fifteen patients entered the study. Of the seven patients randomized to olsalazine, four (57%) improved clinically and by colonoscopic scoring, one showed no improvement in either, and two (29%) withdrew after developing severe watery diarrhea. Of the eight patients treated with placebo, two (25%) improved clinically but were without colonscopic improvement and six (75%) worsened, of whom four withdrew early because of worsening symptoms of colitis. Seven of eight placebo patients were then treated with olsalazine on an open basis. Of these seven, five (71%) improved clinically and colonoscopically and two (29%) withdrew because of severe watery diarrhea. Overall, of 14 patients treated with Olsalazine, nine (64%) improved, one showed no improvement, and four (29%) discontinued because of persistent watery diarrhea. No other serious side effects were noted. Minor side effects included transient diarrhea, flares of acne, and anxiety attacks which resolved despite continuation of the drug.", "Sulfasalazine is accepted therapy for active ulcerative colitis, but side-effects and intolerance are common. Balsalazide is an azo-bonded pro-drug which also releases 5-aminosalicylic acid into the colon, but uses an inert carrier molecule.\n To compare the safety and efficacy of sul- fasalazine, 3 g, with balsalazide, 6.75 g, in the initial daily treatment of mild to moderate ulcerative colitis.\n A randomized, multicentre, double-blind, parallel group study was performed, with a treatment duration of 8 weeks. Patients on previous maintenance treatment were excluded. The trial medication was the sole treatment for the colitis. Efficacy was assessed by patient diaries, symptom assessment, sigmoidoscopic appearance and histology.\n Fifty patients were recruited: 26 allocated to the balsalazide group and 24 to the sulfasalazine group. More patients withdrew due to adverse events in the sulfasalazine group (nine patients vs. one patient in the balsalazide group, P=0.004). Improvement occurred in both groups, with a tendency to a faster response with balsalazide. Of the patients taking balsalazide, 61% achieved clinical and sigmoidoscopic remission.\n Balsalazide, 6.75 g, is effective as the sole treatment for patients with mild to moderately active ulcerative colitis, with significantly fewer withdrawals due to side-effects than in a similar group of patients taking sulfasalazine, 3 g.", "High doses of mesalazine usually result in an inconvenient dosage schedule and reduced compliance. The goal of this trial was to compare the effects of mesalazine 4 g daily given as prolonged-release granules in packets of 1 g with that of prolonged-release tablets of 0.5 g.\n Two hundred twenty-seven patients with mild-to-moderate ulcerative colitis were randomized to treatment with two packets twice daily (Gr-b.i.d.), 1 packet four times daily (Gr-q.i.d.) or 2 tablets four times daily (Ta-q.i.d.) for 8 weeks. A disease activity index (ulcerative colitis disease activity index: UC-DAI) was calculated, and the granules were defined as noninferior to the tablets if the lower limit of the 95% CI for the differences was more than -1 UC-DAI score unit.\n Noninferiority of the granules compared with the tablets was demonstrated. The mean improvement in the UC-DAI in the treatment groups Gr-b.i.d., Gr-q.i.d., and Ta-q.i.d. were 3.2, 2.9, and 2.4, respectively; the proportion of complete responders in the three groups 39%, 37%, and 31%, respectively. There were no differences in side effects.\n Mesalazine 4 g daily given as prolonged-release granules twice and four times daily is at least as effective as prolonged-release tablets four times daily in patients with mild to moderate ulcerative colitis. The patients preferred the twice daily dosing.", "Sulfasalazine is well established in the treatment of active ulcerative colitis. Intolerance to sulfasalazine, however, is a common problem. Balsalazide has been designed to deliver 5-aminosalicylic acid to the colon without the poor tolerability of sulfasalazine.\n To compare the safety and efficacy of balsalazide, 6.75 g daily, with sulfasalazine, 3 g daily, in the treatment of active ulcerative colitis of all grades of severity.\n Balsalazide and sulfasalazine were compared in a multicentre, double-blind, parallel group study over 12 weeks. Patients were stratified for disease severity and topical and/or oral steroids were co-administered where clinically necessary.\n Fifty-seven patients were randomized: 28 to receive balsalazide and 29 to receive sulfasalazine. Significantly fewer patients withdrew from the balsalazide group due to adverse events (2/28 vs. 9/29, P=0.041). These data confirm that balsalazide is better tolerated than sulfasalazine. In patients able to tolerate the treatment, similar improvements were recorded in clinical, sigmoidoscopic and histological assessments in both treatment groups.\n This study confirms the better tolerability of balsalazide compared to sulfasalazine, and supports the use of balsalazide in ulcerative colitis of all grades of severity.", "Balsalazide is a new innovative, mesalamine-containing prodrug that is activated by bacteria in the colon. Balsalazide has been shown previously to be well tolerated and effective in the treatment of acute ulcerative colitis. The aim of this study was to determine the dose-response of balsalazide for efficacy and safety in active, mild-to-moderate ulcerative colitis and to compare this profile with that of mesalamine, pH-dependent, delayed-release tablets.\n A multicenter, randomized, active control, double-blind, double-dummy, dose-response, parallel-group study was performed comparing balsalazide (6.75 g daily), balsalazide (2.25 g daily), and mesalamine (2.4 g daily), administered for 8 wk to 154 patients with active, mild-to-moderate ulcerative colitis as verified by sigmoidoscopy.\n Eight weeks of treatment with 6.75 g of balsalazide daily provided significantly greater improvement than did balsalazide (2.25 g daily) in rectal bleeding (64.7% [6.75-g balsalazide] vs 32.4% [2.25-g balsalazide], p < 0.006), stool frequency (58.8% vs 29.4%, p < 0.006), sigmoidoscopic score (78.9% vs 52.5%, p < 0.015), and Physician's Global Assessment (73.7% vs 51.3%, p < 0.03). The efficacy of balsalazide showed a significantly more rapid onset of action than that of mesalamine (2.4 g daily) (2-wk sigmoidocopic score improvement, 54.7% [6.75-g balsalazide] vs 29.4% [2.4-g mesalamine], p = 0.006) with numerically greater improvement at 8 wk in five of seven measured signs and symptoms. Balsalazide (6.75 g daily) was well tolerated, and the safety profile did not differ significantly from that of balsalazide (2.25 g daily) or mesalamine.\n Eight weeks of treatment with balsalazide (6.75 g daily) is significantly more effective than balsalazide (2.25 g daily) and more rapid in onset than mesalamine (2.4 g daily) in improving signs and symptoms of acute ulcerative colitis. Balsalazide (6.75 g daily) is well tolerated, and the safety profile does not differ from that of balsalazide (2.25 g daily) and mesalamine (2.4 g daily).", "Benzalazine (salicylazobenzoic acid, SAB), a 5-azo derivative of 5-aminosalicylic acid, has been designed as a new therapeutic agent for the treatment of inflammatory bowel disease which might lack the frequent side effects caused by the sulfapyridine moiety of the sulfasalazine molecule (SASP). Here, we report on a prospective, randomized, double-blind comparison of SAB and SASP in patients with an acute relapse of ulcerative colitis. 43 patients with an acute relapse of ulcerative colitis proven by the pertinent endoscopic-macroscopic and histologic criteria were randomized to receive a 6-week course of either 1 g SASP (n = 21) or the equivalent dose of 0.72 g SAB (n = 22) three times a day. Both groups were comparable with respect to demographic data, previous duration and extension of the disease as well as clinical, endoscopic and histologic severity of the relapse. 1 patient on SASP had to be removed from the study due to side effects, while 3 patients on SAB were removed due to rapid worsening of the disease requiring either surgery (1 patient with toxic megacolon) or additional steroid treatment (2 patients). 2 SAB patients were lost to follow-up after substantial improvement had been observed within the first 3 weeks of treatment. In the remaining patients (20 SASP, 17 SAB), stool frequency, stool consistency and macroscopic appearance as well as histology of the diseased mucosa were improved within 6 weeks, with no significant difference between the two groups with respect to any of the parameters recorded. Side effects were recorded in 5 patients on SASP (3 with nausea, 1 with pruritus and 1 with a generalized exanthema) and in 3 patients on SAB (all nausea and vomiting; difference not statistically significant). We conclude that SAB and SASP in equivalent doses are of similar efficacy in the treatment of active ulcerative colitis.", "To study the different therapy for different types of ulcerative colitis (UC) in China.\n Among 102 UC patients, 42 chronic relapse type UC patients were randomly divided into olsalazine sodium treatment group (n=21) and SASP group (n=21). Clinical effects and safety were observed in the 2 groups. Forty-two first episode type UC patients were randomly divided into Heartleaf houttuynia herb treatment group (n=21) and SASP group (n=21). Clinical effects were observed in the 2 groups while ultrastructure of colonic mucosa, ICAM-1 and the pressure of distant colon were studied in Heartleaf houttuynia herb group. Eighteen patients (8 males, 10 females) with refractory UC and unresponsive to high-dose prednisolone and sulfasalazine therapy more than one month were treated with Kangshuanling (7200 U/d). Prednisolone was gradually stopped and sulfasalazine was maintained. Stool frequency, rectal bleeding, colonoscopy, general well-being, histology were observed and CD62p, CD63, CD54, Pgp-170 (flow cytometry), TXA2 (RIA), blood platelet aggregation rate and thrombosis length in vitro were assessed.\n In the 42 chronic relapse type UC patients, the overall clinical effects of olsalazine sodium group (complete remission in 16, improvement in 4, inefficiency in 1) were better than those of SASP group (complete remission in 10, improvement in 4, inefficiency in 7, P<0.05). Symptomatic remission of olsalazine sodium group (complete remission in 15, partial remission in 5, inefficiency in 1) was better than that of SASP group (complete remission in 10, partial remission in 5, inefficiency in 6, P<0.05). The colonoscopic remission of olsalazine sodium group(complete remission in 11, partial remission in 9, inefficiency in 1) was better than that of SASP group (complete remission in 7, partial remission in 8, inefficiency in 6, P<0.05). The histologic remission of olsalazine sodium group (complete remission in 13, partial remission in 7, inefficiency in in 1) was better than that of SASP group (complete remission in 6, partial remission in 10, inefficiency in 5, P<0.05). The side effects of gastrointestinal tract in olsalazine sodium group were less than those of SASP group except for frequency of watery diarrhea. No other side effects were observed in olsalazine sodium group while ALT increase, WBC decrease and skin eruption were observed in SASP group. Two patients relapsed in olsalazine sodium group while 8 cases relapsed in SASP group during the flow-up period (from six months to one year). In the 42 first episode type UC patients, the clinical effect of Heartleaf houttuynia herb group (complete remission in 20, 95.2%; improvement in 1, 4.8%) was better than that of SASP group (complete remission in 15, 72.4%, improvement in 5, 23.8%; inefficiency in 1, 3.8%, P<0.01). The time of stool frequency recovering to normal (5.6+/-3.3 d), and blood stool disappearance (6.7+/-3.8 d) and abdominal pain disappearance (6.1+/-3.5 d) in Heartleaf houttuynia herb group was all shorter than that in SASP group (9.5+/-4.9 d, 11.7+/-6.1 d, 10.6+/-5.3 d, P<0.01). Heartleaf houttuynia herb could inhibit the epithelial cell apoptosis of colonic mucous membrane and the expression of ICAM-1 (45.8+/-5.7% vs 30.7+/-4.1%, P<0.05). Compared with normal persons, the mean promotive speed of contraction wave stepped up (4.6+/-1.6 cm/min vs 3.2+/-1.8 cm/min, P<0.05) and the mean amplitude of the wave decreased (14.2+/-9.3 kPa vs 18.4+/-8.0 kPa, P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, these 2 indexes improved significantly (17.3+/-8.3 kPa, 3.7+/-1.7 cm/min, P<0.05). In normal persons, the postprandial pressure of sigmoid (2.9 +/-0.9 kPa) was higher than that of descending colon (2.0+/-0.7 kPa) and splenic flexure (1.7+/-0.6 kPa), while the colonic pressure (1.5+/-0.5 kPa, 1.4+/-0.6 kPa, 1.3+/-0.6 kPa) decreased significantly (P<0.05) in active UC patients. After treatment with Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold Heartleaf houttuynia herb, the colonic pressure (2.6+/-0.8 kPa, 1.8+/-0.6 kPa, 1.6+/-0.5 kPa) recovered to normal. The pain threshold of distant colon (67.3+/-18.9 mL) in active UC patients decreased significantly compared with that of normal persons (216.2+/-40.8 mL, P<0.05) and recovered to normal after treatment with Heartleaf houttuynia herb(187.4+/-27.2 mL, P<0.05). In the 18 refractory UC patients with platelet activation, after more than 4 wk of combined Kangshuanling and sulfasalazine therapy, 16 patients achieved clinical remission, with a highly significant statistical difference (P<0.01) between pre-and post-treatment mean scores for all disease parameters: stool frequency (8.2/d vs 1.6/d), rectal bleeding (score 2.7 vs 0.3), colonoscopy (score 2.6 vs 1.1), histology (score 12.0 vs 5.0), general well being (score 4.0 vs 0.6) and CD62p (8.0+/-3.1% vs 4.1+/-1.8%), CD63 (6.3+/-2.1% vs 3.2+/-1.6%), TXA2 (548+/-85 ng/L vs 390+/-67 ng/L), platelet aggregation rate (43.2+/-10.7% vs 34.8+/-8.1%), thrombosis length in vitro (2.3+/-0.6 cm vs 1.8+/-0.3 cm), CD54 in blood (26.9+/-6.9% vs 14.4+/-5.1%), CD54 in tissues (51.1+/-6.2% vs 23.1+/-4.1%), Pgp-170 in blood (18.9+/-3.9% vs 10.4+/-2.7%), Pgp-170 in tissues (16.5+/-3.2% vs 10.2+/-2.3%, P<0.01 or 0.05).\n Based on the characteristics of UC cases in China, different therapy should be given to different types of UC with expected satisfactory results.", "Olsalazine (2 g/day) and sulphasalazine (3 g/day) were compared in a double blind three centre trial in 37 patients presenting with first attack of distal colitis. Sigmoidoscopic appearances, rectal biopsies, and symptom and stool diary records were used to assess benefit and adverse effects. Both groups showed a similar decrease in stool frequency (p less than 0.001). The proportion of unformed stools was also decreased, but to a lesser extent (p less than 0.05) in those taking olsalazine (78% v 55%; p less than 0.001) compared with those taking sulphasalazine (72% v 28%; p less than 0.001). There was a diminution in the proportion of stools containing blood in both groups (olsalazine: 61% v 22%; p less than 0.001/sulphasalazine: 67% v 37%; p less than 0.001). Sigmoidoscopic and histological appearances and clinical activity improved significantly and to a similar extent in both groups. Intolerance was encountered in two patients on olsalazine and four on sulphasalazine; intolerance to sulphasalazine being even higher (five of seven patients) in a preliminary study using a dose of sulphasalazine releasing the same amount of 5-aminosalicylic acid as 2 g olsalazine. Olsalazine was at least as effective as sulphasalazine in the treatment of new patients with distal colitis, and in a dose releasing an equivalent amount of 5-aminosalicylic acid was better tolerated.", "5-Aminosalicylates remain important in the treatment of ulcerative colitis, but it is uncertain if the various preparations currently available are equivalent given the different delivery systems that exist. Generic prescription of mesalazine (mesalamine) is therefore inappropriate. Ipocol has recently become available as an alternative to Asacol-MR.\n To compare the two agents in a controlled trial using a non-inferiority design.\n Eighty-eight ulcerative colitis patients with a mild to moderate clinical relapse were randomized to one of the two drugs at a daily dose of 2.4 g for 8 weeks. Safety was the key concern; the primary measured end-point was efficacy as judged from a colitis activity index.\n There were no unexpected adverse events of clinical consequence. The colitis score improved similarly in both patient groups (by 2.3 with Ipocol and by 1.5 with Asacol: not significant), and a similar proportion was in clinical remission at the end of the study (26.1% for Ipocol and 28.6% for Asacol: not significant). Systemic steroids were needed in 11.9% of the Asacol-treated patients compared with 6.5% with Ipocol (not significant).\n It appears appropriate to conclude that, while not identical to Asacol-MR, Ipocol offers a safe and similarly effective alternative.", "To compare the efficacy and tolerability of olsalazine sodium with enteric-coated mesalazine in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis.\n Patients with mild to moderate active ulcerative colitis were randomized to receive either olsalazine sodium, 3 g/day (n = 88), or mesalazine, 3 g/day (n = 80), for up to 12 weeks.\n Of the patients treated with olsalazine sodium, 52.2% achieved endoscopic remission, compared with 48.8% of patients treated with mesalazine. This difference was not significant (P = 0.67). There was a nonsignificant trend for patients with left-sided colitis or a more severe endoscopic grade to achieve remission if they were treated with olsalazine sodium than if they were treated with mesalazine. Both treatments were comparable with respect to clinical activity index and an investigator's global assessment. Seventy patients reported one or more adverse events; adverse events were seen in 45% of olsalazine sodium-treated patients and in 36% of mesalazine-treated patients. Eleven patients treated with olsalazine sodium and nine patients treated with mesalazine withdrew from the study because of adverse events. One patient treated with olsalazine sodium compared with two treated with mesalazine stopped treatment because of diarrhoea. Serious adverse events occurred in three patients treated with olsalazine sodium and in four treated with mesalazine.\n Therapeutic effectiveness and tolerance to the treatment did not differ between olsalazine sodium, 3 g/day, and mesalazine, 3 g/day, in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis within 12 weeks of treatment.", "SPD476 (LIALDA in the US; MEZAVANT in the EU; otherwise known as MMX mesalamine; Shire Pharmaceuticals Inc., Wayne, PA, under license from Giuliani SpA, Milan, Italy) is a novel, once-daily, high-strength (1.2 g/tablet) formulation of mesalamine, utilizing MMX Multi Matrix System (MMX) technology designed to deliver the active drug throughout the colon. We performed a double-blind, multicenter study, comparing MMX mesalamine vs placebo for the treatment of active ulcerative colitis. A delayed-release oral mesalamine (ASACOL; Procter & Gamble, Cincinnati, OH) reference arm was included.\n Three hundred forty-three patients with active, mild-to-moderate ulcerative colitis received MMX mesalamine 2.4 g/day or 4.8 g/day given once daily, ASACOL 2.4 g/day given in 3 divided doses, or placebo for 8 weeks. The primary end point was the proportion of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index of < or =1 with rectal bleeding and stool frequency scores of 0, no mucosal friability, and a > or =1-point reduction in sigmoidoscopy score from baseline).\n A significantly greater proportion of patients receiving MMX mesalamine 2.4 g/day given once daily (40.5%; P = .01) and 4.8 g/day given once daily (41.2%; P = .007) achieved clinical and endoscopic remission at week 8, vs placebo (22.1%). The clinical and endoscopic remission rate for ASACOL (32.6%; P = .124) was not significantly superior to placebo. All active treatments were well-tolerated.\n Once-daily MMX mesalamine was efficacious and well-tolerated for the induction of clinical and endoscopic remission. MMX mesalamine offers effective and convenient mesalamine therapy, potentially improving treatment compliance.", "Preliminary data have shown that delayed release oral mesalamine (Asacol) dosed at 4.8 g/day provided additional efficacy benefit compared to 1.6 g/day in patients with mildly to moderately active ulcerative colitis. Additionally, Asacol dosed at 2.4 g/day has been proved to be more effective than 1.6 g/day. Whether 4.8 g/day of mesalamine (dosed with an investigational 800 mg tablet) is more effective than Asacol 2.4 g/day (dosed with a 400 mg tablet) in patients with moderately active ulcerative colitis is unknown.\n A randomized, double-blind, controlled trial (ASCEND II) was conducted to evaluate the efficacy of 4.8 g/day of mesalamine in adults with active ulcerative colitis. Three hundred eighty-six patients with mild to moderate ulcerative colitis were randomized for treatment with mesalamine 2.4 g/day (400 mg tablet) or 4.8 g/day (800 mg tablet) for 6 wk. The primary efficacy population was 268 patients with moderately active ulcerative colitis treated with 2.4 g/day (n = 139) or 4.8 g/day (n = 129). The primary endpoint was the proportion of patients in each treatment group that achieved overall improvement (\"treatment success,\" defined as either complete remission or a clinical response to therapy) from baseline at week 6.\n Seventy-two percent of patients receiving 4.8 g/day of mesalamine for moderate ulcerative colitis (89/124 patients) achieved treatment success at week 6, compared with 59% of those who received 2.4 g/day (77/130 patients) (p= 0.036). Both regimens were well tolerated. Adverse events and clinically significant changes in laboratory results were similar in both treatment groups.\n Patients with moderately active ulcerative colitis treated with 4.8 g/day of mesalamine (800 mg tablet) are significantly more likely to achieve overall improvement at 6 wk compared to patients treated with 2.4 g/day.", "Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease.\n A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline.\n Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated.\n Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day.", "To evaluate the efficacy and safety of a pH-sensitive, polymer-coated oral preparation of mesalamine in patients with mildly to moderately active ulcerative colitis.\n A multicenter, double-blind, placebo-controlled randomized trial.\n Five university-based medical centers, one inflammatory bowel disease center, and three private practice sites.\n A total of 158 patients with newly or previously diagnosed active ulcerative colitis.\n A pH-sensitive, polymer-coated oral preparation of mesalamine (5-aminosalicylic acid) was used at 1.6 and 2.4 g/d for 6 weeks.\n Efficacy was measured by scores for stool frequency, rectal bleeding, patient's functional assessment, sigmoidoscopic findings, and physician's global assessment. Stringent criteria for disease activity were established prospectively.\n The analysis of protocol-compliant patients showed a significant improvement at 3 weeks in patients taking 2.4 g/d of mesalamine compared with patients taking placebo (32% versus 9%; P = 0.003). At 6 weeks, both the 1.6 g/d (43%) and 2.4 g/d (49%) doses were significantly superior to placebo (23%) (P = 0.03 and P = 0.003, respectively). In addition, more patients worsened in the placebo group compared with the 2.4 g/d group (50% versus 19%; P = 0.003); however, there was no statistically significant difference in worsening between the 1.6 g/d mesalamine group and the placebo group. The oral mesalamine tablet was well tolerated, and no clinically significant changes were observed in hematologic, hepatic, or renal laboratory profiles.\n Colon-targeted oral mesalamine at 2.4 g/d is effective therapy for mildly to moderately active ulcerative colitis. It is well tolerated and should provide a viable therapeutic alternative to sulfasalazine.", "Balsalazide is well tolerated and effective in treating acute ulcerative colitis. VSL#3 is a probiotic cocktail proven to be effective in preventing flare-ups of chronic pouchitis. We compared the efficacy and safety of low-dose balsalazide (2.25 g/day) plus 3 g/day VLS#3 (group A) with medium-dose balsalazide alone (group B) and with mesalazine (group C) in the treatment of mild-to-moderate active ulcerative colitis.\n Ninety patients (30 per group) were randomly enrolled, with a treatment duration of 8 weeks. Efficacy was assessed by symptoms assessment, endoscopic appearance, and histological evaluation.\n Balsalazide/VSL#3 was significantly superior to balsalazide alone and to mesalazine in obtaining remission: 24 patients of group A were in remission [per-protocol: 85.71% (C.I.95%: 62-96), on intention-to-treat: 80% (C.I.95%: 59-91)], while 21 group B [per-protocol: 80.77% (C.I. 95%: 51-82), on intention-to-treat: 77% (C.I.95%: 43-81)] and 16 group C patients [per-protocol: 72.73% (C.I. 95%: 30-75), on intention-to-treat: 53.33% (C.I.95%: 42-62)] were in remission (p<0.02). Balsalazide with or without VSL#3 was better tolerated than mesalazine: two group C patients were withdrawn from the study because of severe side-effects; 1 group A (3.33%), 3 group B (10%) and 4 group C (13.33%) patients experienced slight side-effects. The balsalazide/VSL#3 combination was faster in obtaining remission than balsalazide alone or mesalazine (4, 7.5, and 13 days in groups A, B and C, respectively) and also better in improving all parameters evaluated.\n Balsalazide/VSL#3 may be a very good choice in the treatment of active mild-to-moderate active ulcerative colitis instead of balsalazide alone or mesalazine.", "The efficacy of a capsule formulation of mesalamine was assessed in 374 patients with mild to moderately active ulcerative colitis. Patients, stratified to pancolitis or left-sided disease, received either placebo or mesalamine at 1, 2, or 4 g daily for 8 wk. Efficacy was assessed using clinical improvement--physician global assessment, sigmoidoscopic index, biopsy score, trips to the toilet, and clinical symptoms (abdominal pain, urgency, stool consistency, and rectal bleeding)--and induction of remission (more stringent criteria for physician global assessment, sigmoidoscopic index, and biopsy score). For physician global assessment of treatment benefit, 79% and 84% of patients on the 2-g and 4-g doses of mesalamine, respectively, received treatment benefit, compared with 54% on placebo (p < or = 0.0002). For the physician global assessment of treatment success, both the 2-g and 4-g doses of mesalamine were superior to placebo (57% and 59% of patients, p = 0.0021 and 0.0012, respectively), compared with 36% on placebo. Both the 2-g and 4-g doses produced statistically significant macroscopic (endoscopic) improvement compared with placebo (p < 0.004). The 4-g dose also produced a statistically significant microscopic (histologic) improvement compared to placebo (p < 0.002). Significant improvement compared to placebo was also observed at 2 g and 4 g for the four clinical symptoms and trips to the toilet (p < or = 0.003). Oral mesalamine capsules were significantly superior to placebo for inducing remission, with 29% of patients at 2 g and 29% at 4 g achieving remission by physician global assessment, compared with 12% on placebo. Forty-four percent and 48% of patients receiving 2 g and 4 g of mesalamine, respectively, achieved remission by sigmoidoscopic index (p < 0.05), compared with 31% on placebo. Thirty-nine percent of patients at 4 g daily achieved microscopic remission, compared with 23% on placebo (p < 0.03). Treatment response was not affected by extent of disease or prior steroid or sulfasalazine therapy. These data suggest that controlled-release mesalamine capsules are a safe and effective monotherapy in doses of 2-4 g daily for treating mild to moderately active ulcerative colitis, as well as for inducing remission, regardless of prior oral steroid or sulfasalazine therapy or extent of disease.", "To evaluate the safety and efficacy of a new twice-daily balsalazide disodium 1.1 g tablet dosing regimen (6.6 g/day, three tablets twice daily) for the treatment of mild-to-moderately-active ulcerative colitis (UC).\n In a double-blind, multicenter study patients with symptoms of acute UC and a baseline Modified Mayo Disease Activity Index (MMDAI) score between 6 and 10, inclusive, with a subscale rating of > or =2 for both rectal bleeding and mucosal appearance were randomized to receive 3.3 g of balsalazide or placebo tablets twice daily for 8 weeks. The primary end point was the proportion of patients achieving clinical improvement (> or =3 point improvement in MMDAI) and improvement in rectal bleeding (> or =1 point improvement) at 8 weeks. Safety assessments were conducted from baseline through 2-weeks post-treatment.\n A total of 249 patients (166 balsalazide, 83 placebo) received at least 1 dose of study medication. The mean MMDAI score at baseline was 7.9; 62% of patients had a score > or =8.0 (moderate disease). A significantly larger proportion of patients achieved clinical improvement and improvement in rectal bleeding in the balsalazide group vs. the placebo group (55 vs. 40%, P=0.02). The most common adverse events reported were worsening of UC and headache; both were reported more often in the placebo group.\n Balsalazide disodium 1.1 g tablets administered as 3.3 g twice daily are effective, well tolerated and significantly better than placebo for improving signs and symptoms of mild-to-moderately-active UC. This new formulation with a reduced pill and dosing burden offers the potential to improve convenience and compliance in patients with active UC.", "The therapeutic effectiveness and tolerance of 5-aminosalicylic acid (5ASA), compared with Salazosulphapyridine (SASP) in treatment of ulcerative colitis have been evaluated in 86 patients with the disease at a low or medium phase of activity. After a treatment of six weeks, an improvement was noted in 63.6% (5ASA) and 61.3% (SASP) of these patients. However in no case was a complete remission of the disease observed on the basis of endoscopic inspection. In patients with pancolitis the improvement was lower (37.5% with 5ASA, 40% with SASP). The only side-effect was gastric intolerance, which occurred in 18.1% of the 5ASA and in 19% of the SASP patients. In conclusion we can assume that 5ASA and SASP largely overlap each other as regards both therapeutic effectiveness and occurrence of side-effects.", "SPD476 (MMX mesalazine), is a novel, once daily, high-strength mesalazine formulation (1.2 g/tablet) that utilizes Multi Matrix System (MMX) technology to delay and extend delivery of the active drug throughout the colon.\n To assess the safety and efficacy of MMX mesalazine in patients with mild-to-moderately active ulcerative colitis, in a pilot, phase II, randomized, multicentre, double-blind, parallel-group, dose-ranging study (SPD476-202).\n Thirty-eight patients with mild-to-moderately active ulcerative colitis were randomized to MMX mesalazine 1.2, 2.4 or 4.8 g/day given once daily for 8 weeks. Remission ulcerative colitis-disease activity index (UC-DAI) < or =1, a score of 0 for rectal bleeding and stool frequency, and > or =1 -point reduction in sigmoidoscopy score from baseline was the primary end point.\n Week 8 remission rates were 0%, 31% and 18% of patients receiving MMX mesalazine 1.2, 2.4 and 4.8 g/day respectively. No statistically significant difference in remission was observed between treatment groups. MMX mesalazine 2.4 and 4.8 g/day groups demonstrated greater improvement in overall UC-DAI and component scores from baseline, compared with the 1.2 g/day group.\n MMX mesalazine given as 2.4 or 4.8 g/day once daily is well tolerated and effective for the treatment of mild-to-moderately active ulcerative colitis.", "To evaluate the effect of a controlled-release mesalazine tablet, in patients with ulcerative colitis (UC), a multicenter double-blind study was carried out, using sulfasalazine (500 mg tablet) as the control drug. The mesalazine tablet contained 250 mg of ethyl cellulose-coated mesalazine granules. The patients were assigned to two groups, one to receive mesalazine tablets (1500 mg/day) and a sulfasalazine placebo (group M) and the other to receive sulfasalazine tablets (3000 mg/day) and a mesalazine placebo (group S). The test medications were administered orally for 4 consecutive weeks. The study subjects were selected from among patients with mild to moderate active UC, and 118 patients were enrolled. Concomitant use of steroids and immunosuppressors was prohibited during the study period. Of the 118 patients, 9 dropped out. A total of 109 complete records were thus obtained, 52 in group M and 57 in group S. There was no difference in the improvement of clinical symptoms and endoscopic findings between the two groups. The overall safety, based on adverse reactions and laboratory data, was higher, at 86.5%, for group M (n = 52), compared to 66.7% for group S (n = 57). The general usefulness, based on the improvement and safety, was higher, at 65.3%, for group M (n = 49), compared to 45.6% for group S (n = 57). The controlled-release mesalazine tablet thus appears to be useful in the treatment of mild to moderate active UC.", "5-Aminosalicylate is the gold standard for inducing remission in patients with mildly to moderately active ulcerative colitis. The optimal dose is as yet not defined. Despite some recent developments, the ideal formulation for 5-aminosalicylic acid is still awaited. A new pellet preparation was designed combining slow and delayed release properties. Aims of the study were to find the optimal dose and to test efficacy and safety of a new 5-aminosalicylic acid formulation.\n Three hundred twenty-one patients were included in a double-blind multicenter trial. Inclusion criteria were active ulcerative colitis (Clinical Activity Index [CAI] and Endoscopic Index [EI] according to Rachmilewitz, CAI 6-12; EI >/=4). Three different doses of 5-aminosalicylic acid (0.5 g 3 times a day, 1.0 g 3 times a day, and 1.5 g 3 times a day) were studied for 8 weeks.\n Clinical remission rate (CAI </=4) was highest in the 1.0 g 3 times a day group (66 %), 50% in the 0.5 g 3 times a day group, and 55% in the 1.5 g 3 times a day group. Hierarchical testing showed no significance, indicating a lack of dose response across the 3 mesalamine doses. In addition, times to first clinical response were similar: 26.5 days (1.0 g 3 times a day), 27.5 days (0.5 g 3 times a day), and 21.5 days (1.5 g 3 times a day). Endoscopic improvement was better with 1.0 g mesalamine 3 times a day than with 0.5 g 3 times a day, but overall endoscopic and histologic improvement was not different between treatment groups. Baseline activity, duration, and localization of ulcerative colitis did have some influence on the therapeutic activity, but there was no significant interaction with the dose of the study drug. Safety, with special focus on kidney function, was excellent in all 3 groups.\n There is no significant dose response between mesalamine 1.5 g/day, 3.0 g/day, and 4.5 g/day. The optimal dose to induce remission of ulcerative colitis is 0.5 g 5-aminosalicylic acid 3 times a day. Patients failing with this dose may benefit from an increase of the dose up to 1.0 g 3 times a day, but should also be considered for alternative treatment. A newly developed pellet formulation of 5-aminosalicylic acid has promising efficacy and excellent safety.", "To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk (mesalazine) granules in patients with active ulcerative colitis.\n A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study.\n 54 centres in 13 countries.\n 380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index > or =4 at baseline) were randomised and treated.\n 8-week treatment with either 3 g OD or 1 g TID mesalazine granules.\n Clinical remission (CAI< or =4) at study end.\n 380 patients were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191) and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n = 100; p = 0.0298). About 70% of patients in both treatment groups achieved endoscopic remission, and 35% in the OD group and 41% in the TID group achieved histological remission. About 80% of all patients preferred OD dosing. Similar numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in 61 patients (32.3%) in the TID group, indicating that the two dosing regimens were equally safe and well tolerated.\n OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule. With respect to the best possible adherence of patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis.", "We assessed oral 5-aminosalicylic acid (5-ASA) prepared with a pH-sensitive polymer coating in 87 patients with mildly to moderately active ulcerative colitis in a double-blind, placebo-controlled trial. Patients were randomly assigned to receive 5-ASA at a dosage of either 4.8 or 1.6 g per day or placebo for six weeks. The outcome was monitored by flexible proctosigmoidoscopic examinations and physicians' assessments at three-week intervals and by patients' recordings of daily symptoms. Results showed 24 percent complete and 50 percent partial responses in those receiving 4.8 g of 5-ASA per day as compared with 5 percent complete and 13 percent partial responses in those receiving placebo (P less than 0.0001, rank-sum test). At a dosage of 1.6 g per day, the response was twice as good as with placebo, but the difference did not reach statistical significance (P = 0.51). Age, sex, duration of disease, duration of active symptoms, or extent of disease did not affect the clinical outcome. We conclude that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy, at least in the short term, for mildly to moderately active ulcerative colitis.", "Formulations containing 5-aminosalicylic acid, such as mesalazine, are the gold standard of treatment for mild-to-moderate ulcerative colitis. Current oral regimens require the use of large tablets and frequent dosing to reach the recommended treatment dose. Mesalazine micropellets were designed to allow less frequent dosing in an easier to swallow formulation.\n To compare the efficacy of mesalazine micropellets with the tablet formulation in patients with mild-to-moderate ulcerative colitis.\n This phase 2, double-blind, active-controlled, parallel-group, multiple dose clinical trial randomized 362 patients to either mesalazine micropellets or tablets, at a dosage of 3 g/day. The primary efficacy end-point was the incidence of clinical remission within 8 weeks, defined as the sum of clinical activity index components 1-4 (CAI(C1-4)) < or = 2.\n CAI(C1-4) decreased significantly in both treatment groups within 8 weeks. The micropellet formulation showed confirmatory non-inferiority with statistical significance compared with the tablet formulation, with regard to the incidence of clinical remission (odds ratio in according-to-protocol population 1.008; 95% CI: 0.623-1.632). There was no significant difference in the incidence of adverse events.\n The mesalazine micropellet formulation is as effective as tablets in patients with mild-to-moderate ulcerative colitis, enabling a larger dose to be taken comfortably and conveniently, thereby potentially improving patient compliance, treatment response and quality of life.", "It is not clear what induction dose of mesalamine is optimal for treating patients with mildly and moderately active ulcerative colitis (UC). This study was conducted to determine the efficacy and safety of mesalamine 4.8 g/day compared with 2.4 g/day for the treatment of moderately active UC.\n A multicenter, randomized, double-blind, 6-week, active-control study (ASCEND III) was conducted to assess the noninferiority of delayed-release mesalamine 4.8 g/day (Asacol HD, 800-mg tablet; Procter & Gamble, Pharmaceuticals, Inc, Mason, Ohio) with 2.4 g/day (Asacol, 400-mg tablet; Procter & Gamble Pharmaceuticals, Inc) in 772 patients with moderately active UC. The primary endpoint was treatment success (overall improvement) at week 6, defined as improvement in the Physician's Global Assessment (based on clinical assessments of rectal bleeding, stool frequency, and sigmoidoscopy), with no worsening in any individual clinical assessment.\n The primary objective of noninferiority was met. Seventy percent (273 of 389) of patients who received 4.8 g/day of mesalamine achieved treatment success at week 6, compared with 66% (251 of 383) of patients receiving 2.4 g/day (95% confidence interval for 2.4 g/day minus 4.8 g/day, -11.2 to 1.9). In addition, 43% of patients who received 4.8 g/day mesalamine achieved clinical remission at week 6 compared with 35% of patients who received 2.4 g/day (P = .04). A therapeutic advantage for the 4.8 g/day dose was observed among patients previously treated with corticosteroids, oral mesalamines, rectal therapies, or multiple UC medications. Both regimens were well-tolerated with similar adverse events.\n Delayed-release mesalamine 4.8 g/day (800-mg tablet) is efficacious and well-tolerated in patients with moderately active UC.", "The effect of olsalazine, an analogue of sulphasalazine, consisting of two molecules 5-aminosalicylic acid linked by an azobond has been investigated for the treatment of ulcerative colitis. In a randomised double blind trial we compared 2 g olsalazine with placebo for four weeks. Of the 105 patients, with mild to moderate ulcerative colitis, entered in the trial 52 received olsalazine, and 53 placebo. Treatment had to be terminated prematurely because of untoward effects of olsalazine (mainly diarrhoea) in three patients and treatment failure--that is, increased rectal bleeding in four patients (olsalazine group: one placebo group: three). After four weeks' treatment, a statistically significant improvement in the endoscopic findings in rectum and a positive trend in the reduction of rectal mucus and blood discharge was observed in the patients treated with olsalazine. No statistically significant difference was found for other factors, including stool frequency, consistency, urge to defecate, abdominal pain, and biopsy findings. A comparison between these clinical and endoscopic parameters at study entry and those at study completion (within drug evaluation) showed significant improvement in six of 10 parameters during treatment with olsalazine and in two of 10 during placebo treatment. This difference suggests the significant effect of olsalazine. We conclude that 2 g olsalazine was tolerated as well as placebo, apart from causing diarrhoea in some patients and was slightly superior to placebo during four weeks' treatment of mild to moderate ulcerative colitis. A study with 3 or 4 g olsalazine per day may show a more definite effect." ]

[ "240651", "3615572", "4909377", "4967871", "1582239", "4550211", "4874163", "769027", "6951396", "8018782", "7542829", "362830", "7041515", "7041516", "7041517", "4623599" ]

[ "Comprehesiven clinical studies with thiothixene.", "Zuclopenthixol and perphenazine in patients with acute psychotic states. A double-blind multicentre study.", "Double blind study of clopenthixol and chlorpromazine in acute hospitalized schizophrenics.", "A controlled comparison of clopenthixol and perphenazine in a chronic schizophrenic population.", "Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.", "Haloperidol, clopenthixol, and chlorpromazine in chronic schizophrenia. Chemically unrelated antipsychotics as therapeutic alternatives.", "Clopenthixol: a controlled trial in chronic hospitalized schizophrenic patients.", "An example of European multicenter trials: multispectral analysis of clozapine.", "Serum levels of the isomers of clopenthixol in patients given cis(Z)-clopenthixol or cis(Z)/trans(E)-clopenthixol.", "QEEG alpha 1 changes after a single dose of high-potency neuroleptics as a predictor of short-term response to treatment in schizophrenic patients.", "Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double-blind parallel-group trial.", "Cis(Z)-clopenthixol and clopenthixol (Sordinol) in chronic psychotic patients. A double-blind clinical investigation.", "Cis(Z)-clopenthixol and clopenthixol in the treatment of acute psychoses and exacerbations of chronic psychoses. A double-blind clinical investigation.", "A double-blind clinical investigation of cis(Z)-clopenthixol and clopenthixol in chronic schizophrenic patients.", "Cis(Z)-clopenthixol and haloperidol in chronic schizophrenic patients--a double-blind clinical multicentre investigation.", "The place of thiothixene among the thioxanthenes." ]

[ "nan", "Fifty-four patients with acute psychotic states were included in a double-blind multicentre study of zuclopenthixol and perphenazine given orally. Fourteen patients had not received test preparations for a minimum of 3 weeks as stated in the protocol, and were excluded. The remaining 40 patients received the test preparations for 3 to 12 weeks, with an average of 49 days for patients receiving zuclopenthixol and 45 days for patients receiving perphenazine. Clinical evaluations were done at baseline and at weeks 1, 2, 4, 6, 8, and 12 including the CGI, a CPRS subscale for schizophrenia, and the UKU Side Effects Rating Scale. The patients received on average 37 mg zuclopenthixol or 30 mg perphenazine daily. Statistically, significant reductions on the CGI, severity of illness, and on the CPRS (total score) were found for both drugs when comparing baseline with later scores. No significant differences between the drugs were found. It was also impossible to demonstrate a difference in clinical profile between the two drugs on the basis of the single items on the CPRS. Although small differences between the two drugs were found, as regards number and type of side effects, it is concluded that the pattern of side effects was almost identical in the two treatment groups.", "nan", "nan", "A double-blind, multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics, zuclopenthixol and haloperidol. Patients were allocated at random to receive treatment with one or other of the trial drugs for 8 weeks or until discharge. Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks' treatment. Dosage was chosen and adjusted to the individual patient's condition and response. The average daily doses in Week 4 were 33.5 mg and 10.3 mg, respectively. Clinical assessments, including CGI, BPRS and the UKU side-effect scale, were done at baseline, and after 1, 2, 4, 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8. Both treatments caused a significant reduction in scores with no between-group differences. More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action. Zuclopenthixol caused a significantly greater improvement in 'anxious-depression' factor score than haloperidol. The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups. The extrapyramidal symptoms tended to be transient in the zuclopenthixol group, but not in the haloperidol group. The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute, psychotic patients. There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol.", "nan", "nan", "nan", "The serum levels of the two geometric isomers of clopenthixol and N-dealkylated clopenthixol were estimated in 9 patients, who received cis(Z)-clopenthixol (Cisordinol, Clopixol tabl.) in one period and the double dose of cis(Z)/trans(E)-clopenthixol (Sordinol, Ciatyl) in another period. Nearly equal concentrations of the neuroleptically active isomer, cis(Z)-clopenthixol, were found in the two periods. This finding is in agreement with the clinical experience, but in disagreement with the administered amounts of cis(Z)-clopenthixol, which were larger when the cis(Z)-isomer was given alone. Highly significant correlations were found between dose and mean serum level of cis(Z)-clopenthixol and between dose and area under the serum concentration curves for 8 of the patients, the ninth patient, who had received additional medication showed deviating results. No indication of transformation of cis(Z)-clopenthixol into trans(E)-clopenthixol or vice versa was found. Trans(E)-clopenthixol was found in the serum samples even after administration for one week with the cis(Z)-clopenthixol tablets indicating a relatively long half-life of the trans(E)-isomer. The cis(Z)-isomer of N-dealkyl clopenthixol was found in about the same concentration as cis(Z)-clopenthixol in both periods, while trans(E)-N-dealkyl clopenthixol occurred in about 4 times higher concentrations in patients who had either been given cis(Z)/trans(E)-clopenthixol before they went into the study or had received it in the first period of this study.", "Baseline quantitative electroencephalographic (QEEG) characteristics and their changes after a single test dose of either haloperidol or clopenthixol were investigated in a group of 29 schizophrenics as possible predictors of short-term response to those drugs. On baseline QEEG assessment, responders (R) to subsequent treatment showed fewer slow and more fast activities than nonresponders (NR). A large overlap between R and NR with respect to these measures was observed, however, revealing their practical inadequacy to predict short-term response in individual patients. On the contrary, changes in alpha 1, observed 6 hr after the administration of a single test dose of either haloperidol or clopenthixol, discriminated to a very large extent between R and NR, correctly identifying 17 out of 18 R and 8 out of 10 NR. The QEEG test dose procedure might be used in the selection of the most appropriate antipsychotic drug for individual schizophrenic patients.", "A double-blind, randomized, multi-center, parallel-group study was conducted in Finland to compare the efficacy and safety of risperidone with zuclopenthixol in patients with acute exacerbations of schizophrenia or schizophreniform disorder. Ninety-eight patients were randomly assigned to treatment with risperidone (n = 48) or zuclopenthixol (n = 50), in variable doses, for 6 weeks. The mean daily doses of risperidone and zuclopenthixol at the end of the trial were 8 mg and 38 mg respectively. Efficacy was assessed throughout by the Positive and Negative Syndrome Scale for schizophrenia and Clinical Global Impression. Safety assessments included the Extrapyramidal Symptom Rating Scale, UKU Side-Effect Rating Scale, vital signs, body weight and laboratory screening. The results indicate that risperidone is at least as effective as zuclopenthixol for the treatment of acute schizophrenic episodes, with a trend towards greater improvement in the overall severity of symptoms. The onset of action was significantly shorter with risperidone than with zuclopenthixol. Although the general tolerability of the two drugs was comparable, fewer patients experienced extrapyramidal symptoms with risperidone, so that significantly fewer risperidone-treated patients required antiparkinsonian medication.", "The clinical effect of cis(Z)-clopenthixol has been compared with that of clopenthixol, which is a mixture of the pharmacologically active cis(Z)-isomer and the inactive trans(E)-isomer. In the 2-month double-blind trial were included 57 psychotic patients, mainly schizophrenics. Ratings evaluating severity of illness, therapeutic effect, possible interference of side effects with the patient's functioning, as well as any individual side effects were done at months 0, 1, and 2. The antipsychotic effect of cis(Z)-clopenthixol was found equal to that of clopenthixol whereas the cis(Z)-isomer on a mg/mg basis was twice as active as clopenthixol. Apart from the finding that the unspecific sedative effect appeared to be less marked with cis(Z)-clopenthixol, the type, degree, and frequency of side effects were the same in the two groups of patients. More than half of the patients experienced no side effects.", "The clinical effect of cis(Z)-clopenthixol has been compared with that of clopenthixol, which is a mixture of the pharmacologically active cis(Z)-isomer and the inactive trans(E)-isomer. In the 4-week double-blind trial were included 20 patients with acute psychoses and exacerbations of chronic psychoses, mainly schizophrenics. Ratings evaluating severity of illness, therapeutic effect, possible interference of side effects with the patient's functioning were done at weeks 0, 2, and 4, at which occasions also the BPRS was filled in. All patients improved, most of them so much that their final BPRS-score was less than half their initial score. In conclusion, the antipsychotic effect of cis(Z)-clopenthixol was found equal to that of clopenthixol whereas the cis(Z)-isomer on a mg/mg basis was twice as active as clopenthixol. Side effects were few, similar, and equally frequent in the two groups, extrapyramidal side effects and drowsiness being the most common.", "The therapeutic effect of the neuroleptic cis(Z)-clopenthixol has been compared with that of clopenthixol in mainly chronic schizophrenic patients in a double-blind 8-week trial. Forty-nine of the 54 patients in the trial received clopenthixol in the pre-trial period. Ratings with CGI and a single side effects form were done at weeks 0, 2, 4, 6, and 8. The registration of therapeutic effect at week 8 indicated a symptomatological status quo in both groups of patients while there was a tendency of slightly less interference by cis(Z)-clopenthixol with patient's functioning than by clopenthixol. The ratio of therapeutically equipotent cis(Z)-clopenthixol/clopenthixol doses was found to be 1:2. It is suggested that long-term treatment with clopenthixol advantageously may be replaced by cis(Z)-clopenthixol.", "Sixty-three chronic schizophrenic in-patients were included in the double-blind, double-dummy clinical trial comparing antipsychotic activity and side effects of cis(Z)-clopenthixol and haloperidol. Test treatment was administered at least 8 and in most cases 12 weeks with clinical evaluations including BPRS, NOSIE-30, CGI and single side effects done at weeks 0, 2, 4, 8, and 12. The average end-of-trial doses were 40 mg cis(Z)-clopenthixol and 10 mg haloperidol. Statistically significant improvements of total BPRS-score and Thinking disturbance were registered with both drugs from week 2 onwards. At week 12 when 36 patients were receiving test treatment total BPRS-score was reduced by 31% in the cis(Z)-clopenthixol group and by 17% in the haloperidol group. At week 4 Thinking disturbance was reduced by 32% in the cis(Z)-clopenthixol group and by 16% in the haloperidol group--these findings constituted the only significant difference between test drugs. Compared to the BPRS-results less improvements and no differences between test drugs were registered with NOSIE-30 and CGI. Any trends towards different frequency and severity of side effects were in the favour of cis(Z)-clopenthixol.", "nan" ]

[ "11991271", "12839217", "7029140", "14725657", "10069912", "3883876", "2690721", "4016519", "4701297" ]

[ "Treatment of varicose and telangiectatic leg veins: double-blind prospective comparative trial between aethoxyskerol and sotradecol.", "Long term results of compression sclerotherapy.", "A random controlled trial of two forms of compression bandaging in outpatient sclerotherapy of varicose veins.", "Evaluation of the efficacy of polidocanol in the form of foam compared with liquid form in sclerotherapy of the greater saphenous vein: initial results.", "Evaluation of lidocaine as an analgesic when added to hypertonic saline for sclerotherapy.", "Varicose veins: optimum compression following sclerotherapy.", "Varicose veins: optimum compression after surgery and sclerotherapy.", "Prolonged bandaging is not required following sclerotherapy of varicose veins.", "The treatment of varicose veins in pregnancy by empty vein compressive sclerotherapy." ]

[ "One hundred twenty-nine patients were treated with either polidocanol (POL) or sodium tetradecyl sulfate (STS) to compare the efficacy and adverse sequelae of each agent.\n To determine the safety and efficacy of two sclerosing solutions.\n Each patient's leg veins that did not have incompetence from the saphenofemoral junction (SFJ) were divided into three categories by size (<1 mm, 1-3 mm, 3-6 mm). Each leg was randomly treated with either 0.25%, 0.5%, or 1.5% of STS or 0.5%, 1.0%, or 3% of POL respective of size. An independent, three-panel, blindly randomized photographic examination was obtained pretreatment and at 4 and 16 weeks. Patient satisfaction index and overall clinical improvement assessment were also obtained.\n All patients had an average of 70% improvement and were 70-72% satisfied in all vein categories treated with either solution. There was no significant difference in adverse effects between each group except for a decrease in ulcerations and swelling in the POL group.\n Both STS and POL are safe and effective sclerosing solutions for varicose and telangiectatic leg veins.", "To compare the short and long term results of different techniques of compression sclerotherapy.\n In the past 10 years the authors treated 1622 pts due to chronic venous insufficiency. There were 3 groups of patients: 1) Pts treated by Sigg's technique using Aethoxysclerol, 2) Pts treated by Fegan's technique with Fibrovein, and 3) Pts treated by Fegan's procedure, but using a combination of both sclerosants. In all cases, the techniques of empty vein, bubble air, uninterrupted 6-week compression and forced mobilisation were used.\n In the group of pats. treated by Sigg's procedure, the average cure rate was 67.47% after 6 months, 60.3% after 5 years of follow-up. In Fegan's group this rate was 83.6% after 6 months and 78.54% after 5 year assessment. Statistically, significant differences were found only by the disappearance of varices and reduction of pain in favour of Fegan's technique. In the group of pts treated by Fegan's (Aethoxysclerol + Fibrovein) this rate after 5 years was 86%. The only statistically significant difference was found by the disappearance of varices in favour of Fegan's technique using a combination of 2 detergent sclerosants.\n Sclerotherapy is effective when properly executed in any length of vein no matter how dilated it has become. The recurrences are attributed more to inadequate technique than to the shortcoming of the procedure. Sclerotherapy is miniinvasive, with few complications, and can be repeated on out-patient basis. (Tab. 1, Ref. 22.).", "nan", "Foamed sclerosing agents have been used with enthusiasm by phlebologists for more than 5 decades. Any type of varicose veins can and has been treated with this technique. Numerous publications have stressed the advantages of foamed sclerosing agents on the basis of empiric and experimental criteria and have described various individual techniques to prepare foams. Until now, however, no comparative study for the treatment of large varicose veins with foam or liquid exists.\n The purpose of this first randomized, prospective, multicenter trial was to study the elimination of reflux, the rate of recanalization, and possible side effects of foam sclerotherapy (FS) compared with conventional liquid sclerotherapy for the greater saphenous vein (GSV).\n Eighty-eight patients were randomized into two groups: One group was treated with sclerosing foam (45 patients) and the other with sclerosing liquid (43 cases). Sclerotherapy was performed with direct puncture of the vessel under duplex guidance. The reference sclerosing agent was polidocanol in a 3% solution. The foam was prepared using the Double Syringe System (DSS) method. Only one injection of 2.0 or 2.5 mL liquid or foam was allowed, depending on the diameter of the GSV. Results were assessed according to the protocol.\n Follow-up after 3 weeks showed 84% elimination of reflux in the GSV with DSS foam versus 40% with liquid sclerosant (P < 0.01). At 6 months, six recanalizations were found in the liquid group versus two in the foam group. After 1 year, no additional recanalization was observed with either foam or liquid. Longer term studies are underway. Side effects did not differ between both groups.\n The efficacy of sclerosing foam (DSS) compared with sclerosing liquid in therapy of the GSV is superior, a finding that had already gained empirical recognition but for which there has not been any clinical evidence to date.", "The efficacy of sclerosing agents for the treatment of telangiectasias and reticular veins is well established. The injection of these agents is often associated with pain, and it is not uncommon for sclerotherapists to include lidocaine with the sclerosants in an attempt to reduce the pain associated with treatment. However, there are concerns that this may reduce the overall efficacy of the treatment because of dilution of the sclerosant. Patient comfort and overall outcome associated with treatment using HS with lidocaine (LIDO) versus that using HS alone was compared.\n Forty-two patients were prospectively entered into the study and randomized blindly to sclerotherapy with 23.4% HS or 19% LIDO. Study subjects and treating physicians were blinded to the injection solution used. Injection sites were chosen for veins ranging in size from 0.1 to 3 mm. Photographs of the area to be treated were taken, and the patients rated their pain. They were then observed at regular intervals for four months, and clinical data was collected. Thirty-five subjects completed the full follow-up period, and photographs of the injected area were taken again. Three investigators blinded to the treatment assignment then evaluated the photographs and scored the treatment efficacy according to a standardized system.\n In the HS group, 61.9% (13 of 21) patients rated their pain as none or mild, whereas 90.5% (19 of 21) of patients in the LIDO group had no or mild discomfort. This difference is significant, with a P value of.034. There was no difference in the overall efficacy of treatment between the two groups. The groups had similar rates of vein thrombosis and skin necrosis.\n Although lidocaine is often used with sclerosing agents, there are no previous reports in the literature to evaluate its effectiveness in reducing the pain experienced by the patient. In this study, patients receiving LIDO experienced significantly less discomfort at the time of injection than patients who received HS alone. There were no differences in the effectiveness of treatment or in the incidence of complications between the two groups.", "There is uncertainty regarding the most satisfactory technique of lower limb compression following sclerotherapy for varicose veins. We have compared a standard bandaging technique with a high pressure compression stocking in a randomised trial. Efficacy was judged on the success of injections, complications of the treatment and patient satisfaction. In the stockinged legs 144 of 156 injections were successful, compared with 117 of 147 in the bandaged group (P less than 0.001) (Chi squared). The incidence of superficial thrombophlebitis was also reduced in the stocking group. In addition, the stocking technique costs less in materials than conventional bandaging. We would recommend compression stockings for evaluation in sclerotherapy of varicose veins.", "Graduated compression stockings are used in both surgical and non-surgical treatment of varicose veins. In a trial of high versus low compression stockings (40 mmHg vs 15 mmHg at ankle) after varicose vein surgery, both were equally effective in controlling bruising and thrombophlebitis, but low compression stockings proved to be more comfortable. In a further trial after sclerotherapy, high compression stockings alone produced comparable results to Elastocrepe bandages with stockings. It is concluded that after varicose vein surgery low compression stockings provide adequate support for the leg and that after sclerotherapy, bandaging is not required if a high compression stocking is used.", "Following sclerotherapy of varicose veins, 158 limbs of 154 patients were randomized to be bandaged with either crepe or Coban for 6 weeks each, or with Coban for 3 days only. Objective assessment of vein eradication and subjective evaluation of symptoms 3 months after completion of treatment showed no clear differences between these regimens. Significantly more discomfort was experienced with Coban than crepe when used for 6 weeks. It is suggested that, following sclerotherapy, 3 days is an adequate period of bandaging when using Coban. Such a policy would considerably reduce the inconvenience to patients during treatment.", "nan" ]

[ "21122499", "8964395" ]

[ "Clinical trial: Preliminary efficacy and safety study of a new Budesonide-MMX® 9 mg extended-release tablets in patients with active left-sided ulcerative colitis.", "Oral budesonide versus prednisolone in patients with active extensive and left-sided ulcerative colitis." ]

[ "Ulcerative colitis (UC) is a chronic inflammatory disease with relapses. Many patients need systemic corticosteroids to induce clinical remission.\n Efficacy and safety of Budesonide-MMX® 9 mg tablets, a new oral, extended-release formulation, were evaluated in patients suffering from active, left-sided UC with colitis activity index (CAI) <14.\n 36 patients were treated once daily for 4 weeks with Budesonide-MMX® 9 mg tablets or placebo. In an additional 4-week period, all patients received Budesonide-MMX®. CAI, endoscopic index and histology were assessed after 4 and 8 weeks. Primary end-point was remission, and/or CAI reduction by 50% after 4 weeks. Morning cortisol was assayed after 4 and 8 weeks, and a short ACTH-test was performed at week 8.\n 32 patients were analysed. After 4 weeks, 47.1% of the patients in the Budesonide-MMX® 9 mg tablets group achieved the primary end-point vs. 33.3% of patients on placebo. In addition, 47.1% of budesonide patients and another 33.3% of placebo recipients improved without remission by 4 weeks. The CAI reduction was significant with Budesonide (p<0.0001) tablets and not with placebo (p=0.1). Neither morning cortisol nor pituitary-adrenal axis was more frequently suppressed with Budesonide tablets than with placebo.\n Budesonide-MMX® 9 mg tablets induced a fast and significant clinical improvement of active left-sided UC without suppression of adrenocortical functions and without important toxicity EudraCT number 2004-000896-33.\n Copyright © 2009 Elsevier B.V. All rights reserved.", "Systemic glucocorticosteroids (GCSs) have proven efficacy in active ulcerative colitis but cause undesired systemic side effects. Therefore, new GCSs with high topical activity and a high rate of metabolism may be of clinical value in this condition. The aim of this study was to explore the efficacy and safety of the topically acting GCS budesonide in an oral controlled-release formulation in extensive or left-sided, mild to moderately active ulcerative colitis.\n A 9-week, randomized, double-blind, controlled trial was performed, and treatments with 10 mg budesonide or 40 mg prednisolone daily, both gradually tapered, were compared. Endoscopic improvement and effect on endogenous plasma cortisol were assessed.\n Thirty-four patients were administered budesonide, and 38 patients were administered prednisolone. Mean endoscopic scores improved significantly in both groups but without difference between the groups. Five patients in the budesonide group and 7 patients in the prednisolone group deteriorated and were withdrawn from the study. Morning plasma cortisol levels were suppressed in the prednisolone group (entry, 449 nmol/L; 2 weeks, 116 nmol/L; 4 weeks, 195 nmol/L) but were unchanged in the budesonide group.\n The GCS budesonide administered in an oral controlled-release formulation seems to give an overall treatment result in active ulcerative colitis approaching that of prednisolone but without suppression of plasma cortisol levels. This concept merits further evaluation." ]

[ "3941301", "3812046", "3369332", "16766441", "832925", "396255", "1194487", "6377845", "18569754" ]

[ "A randomized controlled trial of hypnotherapy for smoking cessation.", "Treatment effectiveness of hypnosis and behaviour therapy in smoking cessation: a methodological refinement.", "Use of single session hypnosis for smoking cessation.", "Intensive hypnotherapy for smoking cessation: a prospective study.", "The effects of rapid smoking and hypnosis in the treatment of smoking behavior.", "Variables of hypnosis which are related to success in a smoking withdrawal program.", "Comparison of hypnosis plus counseling, counseling alone, and hypnosis alone in a community service smoking withdrawal program.", "A randomized trial comparing smoking cessation programs utilizing behaviour modification, health education or hypnosis.", "Hypnosis for smoking cessation: a randomized trial." ]

[ "A randomized controlled study in a family practice setting was conducted on the use of hypnosis in helping people quit smoking. In the hypnosis group 21 percent of patients quit smoking by the three month follow-up compared with 6 percent in the control group. By six months there were no significant differences between the two groups, and at one year 22 percent in the hypnosis group and 20 percent in the control group had quit. The only significant predictor of success with quitting was having a college education.", "Studies in smoking cessation have generally failed to adequately control for active treatment effects and have assumed that measures of smoking behaviour (i.e., estimated smoking rate, self-monitoring and chemical analysis) are equally reliable measures. Sixty smokers were randomly assigned to one of four different smoking cessation treatment groups: hypnosis, focussed smoking, attention placebo and a waiting list control. Subjects were asked to estimate and monitor their own smoking behaviour. Blood samples were also taken for thiocyanate analysis before treatment. Smoking rates were similarly measured directly, at 3 months and 6 months after treatment. The results indicate that the three measures of smoking behaviour were all highly correlated. No significant differences were found between treatments, directly after treatment or at the 3- and 6-month follow-ups. These results suggest that active treatment effects may not be responsible for behavioural change in a smoking cessation program. The implications of these findings are discussed.", "Twenty of sixty volunteers for smoking cessation were assigned to single-session hypnosis, 20 to a placebo control condition, and 20 to a no-treatment control condition. The single-session hypnosis group smoked significantly less cigarettes and were significantly more abstinent than a placebo control group and a no treatment control group at posttest, and 4-week, 12-week, 24-week and 48-week follow-ups.", "This study reports on a prospective pilot trial of intensive hypnotherapy for smoking cessation. The hypnotherapy involved multiple individual sessions (8 visits) over approximately 2 months, individualization of hypnotic suggestions, and a supportive therapeutic relationship. Twenty subjects were randomly assigned to either an intensive hypnotherapy condition or to a wait-list control condition. The target quitting date was 1 week after beginning treatment. Patients were evaluated for smoking cessation at the end of treatment and at Weeks 12 and 26. Self-reported abstinence was confirmed by a carbon-monoxide concentration in expired air of 8 ppm or less. The rates of point prevalence smoking cessation, as confirmed by carbon-monoxide measurements for the intensive hypnotherapy group, was 40% at the end of treatment; 60% at 12 weeks, and 40% at 26 weeks (p < .05).", "nan", "nan", "nan", "The purpose of this study was to determine the efficacy of hypnosis, health education, and behaviour modification programs for cigarette smoking cessation. A randomized clinical trial comparing these three programs and a control group was conducted in 168 volunteers. Follow-up data three weeks after completion was available in 140 subjects. Each program showed significant reductions in reported cigarette consumption and serum thiocyanate levels, an indicator of long-term cigarette consumption, compared to entry and to the control group. However, there were no significant differences between the hypnosis, health education, or behaviour modification groups with respect to the proportion who reported quitting smoking, the number cigarettes smoked or change in serum thiocyanate levels. Reported cigarette consumption ascertained six months later again showed no significant differences between these three approaches. Factors such as subject age, age at starting cigarette smoking, educational level, marital status, spouse or partners smoking did not identify subgroups with differences between treatment responses. Thus, hypnosis, health education, and behaviour modification are each effective programs for changing cigarette smoking and each is equally effective in this regard.", "The purpose of this study was to determine whether hypnosis would be more effective in helping smokers quit than standard behavioral counseling when both interventions are combined with nicotine patches (NP). A total of 286 current smokers were enrolled in a randomized controlled smoking cessation trial at the San Francisco Veterans Affairs Medical Center. Participants in both treatment conditions were seen for two 60-min sessions, and received three follow-up phone calls and 2 months of NP. At 6 months, 29% of the hypnosis group reported 7-day point-prevalence abstinence compared with 23% of the behavioral counseling group (relative risk [RR] = 1.27; 95% confidence interval, CI 0.84-1.92). Based on biochemical or proxy confirmation, 26% of the participants in the hypnosis group were abstinent at 6 months compared with 18% of the behavioral group (RR = 1.44; 95% CI 0.91-2.30). At 12 months, the self-reported 7-day point-prevalence quit rate was 24% for the hypnosis group and 16% for the behavioral group (RR = 1.47; 95% CI 0.90-2.40). Based on biochemical or proxy confirmation, 20% of the participants in the hypnosis group were abstinent at 12 months compared with 14% of the behavioral group (RR = 1.40; 95% CI 0.81-2.42). Among participants with a history of depression, hypnosis yielded significantly higher validated point-prevalence quit rates at 6 and 12 months than standard treatment. It was concluded that hypnosis combined with NP compares favorably with standard behavioral counseling in generating long-term quit rates." ]

[ "11340701", "9648698" ]

[ "Intranasal beclomethasone dipropionate in the treatment of common cold.", "The common cold: effects of intranasal fluticasone propionate treatment." ]

[ "Sinusitis is usually considered a complication of viral rhinitis. Virus infections in the upper respiratory tract lead to mucosal swelling, which may obstruct paranasal sinus outflow, resulting in infection in the paranasal sinuses. Topical nasal steroids have been found beneficial in a variety of acute and chronic nasal conditions including allergic and nonallergic rhinitis and chronic rhinosinusitis. The purpose of this study was to examine whether the intranasal inhalation powder beclomethasone dipropionate (BDP) 400 micrograms/day treatment has a beneficial or harmful effect on symptoms and signs of common cold, and whether or not it can prevent common cold complications. A total of 54 patients were randomized, 26 into the placebo-group and 28 into the BDP group. During the 14-day follow-up, there were on an average 10.3 symptomatic days in the placebo group and 10.7 days in the BDP group (p = 0.72). The use of intranasal BDP in the treatment of common cold neither reduced symptoms caused by inflammation nor did it shorten the recovery time. On the other hand, because BDP does not increase the risk of complications or significantly prolong the recovery during the common cold, there is no need to discontinue its use in the patients with allergic rhinitis or nasal polyposis.", "A double-blind, randomized, placebo-controlled trial was conducted to study the effect of the intranasal corticosteroid, fluticasone propionate (FP), in the naturally occurring common cold.\n One hundred ninety-nine young adults received high-dose FP (200 microg four times daily) or placebo beginning 24 to 48 hours after onset of the common cold for 6 days. All symptoms were recorded on diary cards on days 1 to 20, and clinical examinations were carried out on days 1, 7, and 21. Nasopharyngeal aspirates were collected on days 1 and 7 for detection of rhinoviruses (found in 105 subjects) and Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis (found in 52 subjects) in the nasopharynx.\n In general, FP treatment had no clinically recognizable effects on the symptoms of the common cold, although it significantly reduced nasal congestion and cough on some study days. After treatment, rhinoviruses were cultured more often in the FP treatment group (37% vs 14%, p < 0.001), but this had no effect on the symptoms of common cold. FP treatment produced no changes in the colonization of pathogenic bacteria in the nasopharynx. Some symptoms of common cold were significantly more severe during days 1 to 10 (p < 0.05) in subjects found to have positive cultures for S. pneumoniae, H. influenzae, or M. catarrhalis in the nasopharynx on day 1 (n = 33).\n FP treatment does not have any marked effects on the symptoms of the common cold. FP treatment induced prolonged shedding of viable rhinoviruses. Some symptoms of the common cold were significantly more severe in subjects with pathogenic bacteria in the nasopharynx." ]

[ "6733063", "6367345", "861482", "8262083", "6338992", "3672322", "4016545", "2645846", "6998538", "679555", "6208877", "2483018", "5117008", "1702235", "8682818", "788855" ]

[ "The efficacy of graduated compression stockings in the prevention of deep vein thrombosis after major gynaecological surgery.", "Calf compression for prevention of thromboembolism following hip surgery.", "The efficacy of graduated compression stockings in the prevention of deep vein thrombosis.", "Graduated compression stockings in the prevention of deep vein thrombosis in patients with acute myocardial infarction.", "The use of graduated compression stockings in the prevention of postoperative deep vein thrombosis.", "Regimen for improved effectiveness of intermittent pneumatic compression in deep venous thrombosis prophylaxis.", "Heparin with and without graded compression stockings in the prevention of thromboembolic complications of major abdominal surgery: a randomized trial.", "Prevention of deep vein thrombosis in potential neurosurgical patients. A randomized trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control.", "Low dose heparin and compression stockings in the prevention of postoperative deep venous thrombosis.", "Efficacy of graded-compression antiembolism stockings in patients undergoing total hip arthroplasty.", "The thromboprophylactic effect of graded elastic compression stockings in combination with dextran 70.", "Thromboprophylaxis in hip arthroplasty. Dextran with graded compression or preoperative dextran compared in 150 patients.", "Postoperative venous thrombosis and the effectiveness of prophylactic measures.", "Prophylaxis of deep venous thrombosis after acute abdominal operation.", "Graded compression stockings for prevention of deep-vein thrombosis after hip and knee replacement.", "Graded compression for preventing deep venous thrombosis." ]

[ "The efficacy of graduated compression stockings in the prevention of deep vein thrombosis (DVT) after major gynaecological surgery was investigated in a controlled randomized prospective trial in 196 patients who were greater than 35 years of age. The stockings were worn by 104 of the 196 patients throughout their stay in hospital, the other 92 patients did not wear the stockings (control group). All the patients were scanned for DVT postoperatively with the 125I-labelled fibrinogen test. None of the 104 patients who wore the stockings developed a thromboembolism, but four of the 92 control patients who did not wear the stockings had DVT. This difference between the two groups was statistically significant.", "A prospective, randomized trial of the effect of graded compression of the calf was done in 62 patients operated on electively for hip disease. After total hip arthroplasty, compression reduced the number of positive fibrinogen uptake tests by two-thirds, significant only in males, who seem to run a higher risk of thrombosis than females.", "The incidence of deep venous thrombosis (DVT) was studied by the 125I-fibrinogen technique in 70 patients who had had major abdominal operations and who were wearing graduated static compression stockings on one leg, the patient's other leg being used as a control. In the whole group 7 patients developed bilateral DVT, 19 patients developed unilateral DVT in the control leg and only one patient developed unilateral DVT in the stockinged leg. The difference between stockinged and control legs was highly significant (P = 0-0003). In the 19 patients with malignant disease the incidence of DVT in the stockinged leg remained significantly less (P = 0-037). It is concluded that graduated static compression stockings do reduce the incidence of postoperative deep venous thrombosis.", "Venous volume (venous capacity) of the calf is low in patients with acute myocardial infarction, who also have a high risk of deep vein thrombosis (DVT). The effect of graduated compression stockings on the venous volume and on the incidence of DVT was therefore studied in 80 patients aged 70 years and above with acute myocardial infarction. Graduated compression stockings were randomly fitted to one leg, the other serving as a control, after which the venous volume was measured by strain gauge plethysmography. The incidence of DVT was measured by the 125I fibrinogen uptake test. Venous volume was significantly higher in legs treated with graduated compression stockings compared to control legs. DVT developed in eight control legs but not in any leg treated with graduated compression stockings (P = 0.003). DVT was also significantly more frequent in women compared to men and the majority of DVT developed in legs with very low venous volume values.", "The efficacy of graduated compression stockings in the prevention of postoperative deep vein thrombosis was studied in a randomized, prospective, controlled trial of 200 patients, aged 40 years and over, undergoing abdominal surgery (100 for benign disease, 100 for malignant conditions). Deep vein thrombosis was diagnosed by the 125I-fibrinogen test. The incidence of deep vein thrombosis was 35.9 per cent in the control group (103 patients) and 15.5 per cent in the stockinged group (97 patients) (P less than 0.025). In the patients with benign disease, deep vein thrombosis developed in 24.5 per cent of the control limbs and 6.1 per cent of stockinged limbs (P less than 0.005); in patients with malignant disease the similar figures were 27.9 and 11.5 per cent (P less than 0.05). Increasing age did not alter the efficacy of the stockings. It is concluded that graduated compression stockings provide a safe and effective method of prophylaxis against deep vein thrombosis.", "The incidence of deep venous thrombosis (DVT) was assessed in a series of 78 patients undergoing major surgical operations to compare the prophylactic effectiveness of intermittent sequential pneumatic compression alone with the simultaneous use of graduated compression stockings and intermittent sequential pneumatic compression. The diagnosis of DVT was determined with the I-125 fibrinogen-uptake test, Doppler ultrasound, maximum venous outflow by strain-gauge plethysmography, and contrast venography. The incidence of DVT in nonstockinged legs was 9% while that in the stockinged legs was 1%. The simultaneous use of graduated elastic compression stockings and intermittent pneumatic compression is more effective than pneumatic compression alone in the prevention of postoperative DVT.", "One hundred and seventy-six patients scheduled for elective major abdominal surgery were randomized to two prophylactic regimens to prevent postoperative thromboembolism. All patients were screened with the 125I-labelled fibrinogen uptake test, and thromboembolism was verified by ascending phlebography and/or perfusion/ventilation lung scintigraphy. In the group of patients receiving low-dose heparin treatment (5000 units twice daily subcutaneously) 12 per cent developed thromboembolic complications. In the other group, where low-dose heparin treatment was supplemented with graded compression stockings only 2 per cent developed thromboembolism. It is concluded that the combination of low-dose heparin and the use of graded compression stockings is superior to heparin alone in preventing thromboembolism following major abdominal surgery.", "In a randomized trial of neurosurgical patients, groups wearing graduated compression stockings alone (group 1) or graduated compression stockings plus intermittent pneumatic compression (IPC) (group 2) were compared with an untreated control group in the prevention of deep vein thrombosis (DVT). In both active treatment groups, the graduated compression stockings were continued for 14 days or until hospital discharge, if earlier. In group 2, IPC was continued for seven days. All patients underwent DVT surveillance with iodine 125-labeled fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became abnormal. Deep vein thrombosis occurred in seven (8.8%) of 80 patients in group 1, in seven (9.0%) of 78 patients in group 2, and in 16 (19.8%) of 81 patients in the control group. The observed differences among these rates are statistically significant. The results of this study indicate that graduated compression stockings alone or in combination with IPC are effective methods of preventing DVT in neurosurgical patients.", "The frequency of deep venous thrombosis (DVT) was studied in 98 patients undergoing major abdominal surgery. All the patients received low dose heparin prophylaxis 5000 i.u. every 12 h for 5-7 days. In each patient, a graduated compression stocking was also worn and randomly allocated to one of the legs and the other leg served as a control. DVT was diagnosed by the 125I-fibrinogen method. Four patients developed bilateral DVT and 8 patients unilateral DVT, all of whom developed it in the control leg. The difference in unilateral DVT between stockinged and control legs was significant (P < 0.004). It is concluded that a combination of low dose heparin and graduated compression stockings is more effective than low dose heparin alone in reducing the frequency of postoperative DVT. It is suggested that this combination of prophylaxis might be of value in high risk patients.", "A prospective randomized trial evaluated graded-compression antiembolism stockings for prevention of leg vein thrombosis as assessed by Doppler ultrasound, in patients undergoing total hip replacement. The study was terminated after the evaluation of 18 patients revealed a significantly greater incidence of deep vein thrombosis, documented by phlebography, in patients without stockings (5 of 10) compared to those with stockings (none of 8, p less than 0.03). Three of the patients with thrombosis developed pulmonary emboli. Although the sample size of this study is small, the implication that graded-compression stockings reduce the incidence of leg vein thrombosis is strong and is supported by the results of other recent trials. These findings are at variance with earlier studies which failed to document efficacy of elastic stockings, which involved products which did not provide graded limb compression.", "We studied 80 patients who were older than 50 years of age to determine if graded elastic compression stockings reduced the frequency of postoperative thrombosis in patients undergoing dextran 70 prophylaxis. All of the patients received a total of 2,000 mL of dextran 70 during three days; according to a random table, each of the patients had one leg encased in a graded compression stocking for one week. Thrombosis development was screened with the fibrinogen I 125 test. Eight patients manifested thrombosis-one in the thigh and seven in the calf--localized to the unstockinged leg, a frequency significantly greater than the zero frequency in the stockinged leg. No untoward effects of this combination prophylaxis were noted.", "Totally, 150 patients, subjected to total hip arthroplasty, were randomly allocated into three prophylactic groups with either conventional dextran alone or with additional graded compression stockings or with additional preoperative administration of dextran. The overall frequency of deep venous thrombosis (DVT), as studied by radioactive fibrinogen uptake test and ascending phlebography of the operated on thigh was in the conventional dextran group 46 percent, the additional stockinged group 30 percent, and in the additional preoperative dextran group 52 percent. In the stockinged group, there was a lower frequency of DVT in the nonoperated on leg as well as, on an average, about 350 mL less peroperative bleeding as compared with the other two groups. No adverse reaction occurred from dextran administration. Increased and prolonged postoperative administration of dextran decrease the number of femoral DVTs.", "nan", "Two hundred and forty-five patients who underwent acute extensive abdominal operations were randomized into three regimens to achieve optimal prophylaxis of postoperative thromboembolic complications. All of the patients were screened by the 125I-fibrinogen uptake test for seven days and if the phlebographic findings were positive. Of 81 patients receiving low dose heparin, 12 had thromboembolism. Of 79 receiving a combination of low dose heparin and graded compression stockings, two had thromboembolism, and of 85 receiving a combination of dextran and graded compression stockings, 13 had this complication. This difference is significant in favor of the second treatment (p = 0.013). It is concluded that the combination of low dose heparin and graded compression stockings is an effective way to prevent thromboembolism after acute abdominal operations.", "We performed a prospective, randomised controlled trial in 177 patients who were having either total hip or knee replacement, to evaluate the use of both above- and below-knee graded compression stockings in the prevention of deep-vein thrombosis (DVT). With above-knee stockings, we found no significant reduction of the overall, proximal or major calf (> 5 cm) DVT rates. With below-knee stockings, the overall thrombosis rate was similar to that of the control group but the stockings appeared to have altered the pattern of thrombosis. Patients who had total hip replacement and wore below-knee stockings had a significantly higher rate of proximal or major calf DVT (p = 0.03). This pattern was reversed in patients with total knee replacement who developed a significantly lower rate of proximal or major calf DVT with below-knee stockings (p < 0.05). Our results showed that, with the exception of below-knee stockings in knee replacement patients, graded compression stockings were ineffective in preventing DVT after hip or knee replacement surgery.", "The physiological effects of static compression of the leg have recently been reinvestigated. Graded compression extending from the ankle to the upper thigh produces the maximum increase in velocity of femoral vein blood flow and the maximum decrease in clearance times of contrast media and radioisotopes from the deep veins of the calf. This type of compression may be easily produced by a specially designed elastic stocking. Graded compression was used in a controlled clinical trial of 98 patients undergoing major operations to assess its effect on isotopically diagnosed deep vein thrombosis. The incidence of deep vein thrombosis was 49% in the control group and 23% in the treated groups. No complications were caused by the stockings. Carefully designed and correctly applied static compression is a safe and effective method of reducing the incidence of deep vein thrombosis." ]

[ "3365857", "3089466", "3693764", "8142334" ]

[ "Immune response of the atopic woman and foetus: effects of high- and low-dose food allergen intake during late pregnancy.", "Effect of maternal dietary exclusion on breast fed infants with eczema: two controlled studies.", "Development of atopic disease in babies whose mothers were receiving exclusion diet during pregnancy--a randomized study.", "The immunological and long-term atopic outcome of infants born to women following a milk-free diet during late pregnancy and lactation: a pilot study." ]

[ "The influence of the mother's consumption of cows' milk and hens' egg on the immune response (IgE, IgG) in the mother and foetus was studied in 165 pregnant women with atopical respiratory disease with an allergy to pollen and/or animal dander. The women were randomly allocated to four diets ranging from a diet free from hens' egg and cows' milk to a diet containing intake of one egg and one litre of milk daily during the third trimester. No significant differences in cord blood IgE levels were noted in spite of differences in maternal diet, and no specific IgE antibodies to ovalbumin, ovomucoid and betalatoglobulin were found in the cord blood. The mother's IgG antibody concentrations to ovalbumin, ovomucoid and betalactoglobulin were influenced by her diet, but cord blood IgG antibody levels to the selected food allergens were unaffected. The data presented on the IgE and IgG antibody levels to ovalbumin, ovomucoid and betalactoglobulin in cord blood suggest that changes in maternal diet during the last trimester of pregnancy in order to prevent atopic sensitization in utero are less likely to affect the foetus than previously supposed.", "Thirty seven breast fed infants with eczema were studied to see whether changes in their mothers' diets affected their skin condition. Nineteen mothers and babies took part in a double blind crossover trial of exclusion of egg and cows' milk, and 18 took part in open exclusion of 11 foods followed by double blind challenge to those mothers whose infants seemed to respond. Babies were examined at the beginning and end of each dietary period, and the extent and severity of the rash were given a numerical score. The eczema improved in six infants when their mothers avoided egg and cows' milk and worsened again when these were reintroduced. Two infants suffered gastrointestinal reactions after maternal ingestion of egg and cows' milk, one developing colitis. Maternal dietary exclusion seems to benefit some breast fed babies with eczema.", "In a prospective, randomized study, we have monitored the effect of maternal abstention from cow's milk and egg on the development of atopy in babies. Two hundred twelve women were followed from midpregnancy. We report the occurrences of allergies in their babies up to 18 months of age, as assessed by skin prick testing, determination of serum IgE, questionnaires, and blinded physical examination by a pediatric allergist. Whatever the method that was used, there was no statistically significant difference between babies whose mothers received the \"diet\" or the \"nondiet.\" Other factors known to influence the risk of atopy like heredity, sex, month of birth, breast-feeding, and exposure to tobacco smoke, animal dandruff, and solid food did not differ between the groups. The mothers receiving the exclusion diet, by their own choice, had diminished their intake of milk and egg during lactation also, and therefore, their babies were significantly less exposed to cow's milk before 6 months. Still, atopy was equally abundant among their children. Thus, maternal elimination diet during late pregnancy did not protect the baby against allergy.", "Infants born to atopic parents have been found to be at high risk of allergy development. The present study investigated the effect of a maternal milk-free diet during late pregnancy and lactation on the immune response and allergy incidence in at-risk and control infants. Atopic mothers were randomly allocated into an intervention group (n 12) or an unrestricted-diet group (n14) and compared with non-atopic mothers following an unrestricted diet (n 12). The intervention involved a maternal milk-free diet during late pregnancy and lactation. Infants were followed up for 18 months postnatally. A significant fall in maternal serum beta-lactoglobulin (beta-Lg)-immunoglobulin G (IgG) antibody levels (P < 0.05) was observed after a 7-week milk-exclusion diet. In maternal and cord serum samples the levels of beta-Lg-IgG and alpha-casein-IgG antibodies were significantly correlated (r 0.89, P < 0.0001 and r 0.71, P < 0.001 respectively). Higher levels of beta-Lg-IgG (P < 0.05) were observed in the cord serum samples compared with paired maternal serum samples. Single-blind allergy assessment by a paediatrician at 12 and 18 months showed that the infants born in the non-atopic group had a significantly lower allergy incidence compared with the infants born in the atopic group following an unrestricted diet (P < 0.008 and P < 0.02 respectively). The allergy incidence in the infants born in the atopic diet group was significantly lower compared with that of the atopic group following an unrestricted diet (P < 0.04). It was observed that the atopic nature of the parents significantly affected the allergy incidence in their children. A trend towards a beneficial effect of a maternal milk-free diet during late pregnancy and lactation was also observed in infants born to atopic parents." ]

[ "8336751", "7403713", "10716478", "9159625", "326013", "6803719" ]

[ "A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement.", "Reduction of platelet activity in patients with prosthetic heart valves.", "Early and long-term (one-year) effects of the association of aspirin and oral anticoagulant on thrombi and morbidity after replacement of the mitral valve with the St. Jude medical prosthesis: a clinical and transesophageal echocardiographic study.", "Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical prosthetic heart valves.", "Prevention of arterial thromboembolism with acetylsalicylic acid. A controlled clinical study in patients with aortic ball valves.", "[Prevention of systemic thromboembolic accidents in patients with artificial valve prostheses. Prospective study of an antivitamins K-dipyridamole combination]." ]

[ "Despite the use of warfarin, major systemic embolism remains an important complication in patients with heart-valve replacement. Although the addition of antiplatelet agents has the potential to reduce this complication, their efficacy and safety when given in combination with warfarin are uncertain.\n In a randomized, double-blind, placebo-controlled trial, we assessed the efficacy and safety of adding aspirin (100 mg per day) to warfarin treatment (target international normalized ratio, 3.0 to 4.5) in 370 patients with mechanical heart valves or with tissue valves plus atrial fibrillation or a history of thromboembolism.\n A total of 186 patients were randomly assigned to aspirin and 184 to placebo, and they were followed for up to 4 years (average, 2.5). Major systemic embolism or death from vascular causes occurred in 6 aspirin-treated patients (1.9 percent per year) and 24 placebo-treated patients (8.5 percent per year) (risk reduction with aspirin, 77 percent; 95 percent confidence interval, 44 to 91 percent; P < 0.001). Major systemic embolism, nonfatal intracranial hemorrhage, or death from hemorrhage or vascular causes occurred in 12 patients assigned to aspirin (3.9 percent per year) and 28 patients assigned to placebo (9.9 percent per year) (risk reduction, 61 per cent; 95 percent confidence interval, 24 to 80 percent; P = 0.005); major systemic embolism or death from any cause occurred in 13 patients (4.2 percent) and 33 patients (11.7 percent), respectively (risk reduction, 65 percent; 95 percent confidence interval, 33 to 82 percent; P < 0.001); and death from all causes occurred in 9 patients (2.8 percent) and 22 patients (7.4 percent), respectively (risk reduction, 63 percent; 95 percent confidence interval, 19 to 83 percent; P = 0.01). Bleeding occurred in 71 patients in the aspirin group (35.0 percent), as compared with 49 patients in the placebo group (22.0 percent) (increase in risk, 55 percent; 95 percent confidence interval, 8 to 124 percent; P = 0.02); major bleeding occurred in 24 and 19 patients, respectively (increase in risk, 27 percent; 95 percent confidence interval, -30 to 132 percent; P = 0.43).\n In patients with mechanical heart valves and high-risk patients with prosthetic tissue valves, the addition of aspirin to warfarin therapy reduced mortality, particularly mortality from vascular causes, together with major systemic embolism. Although there was some increase in bleeding, the risk of the combined treatment was more than offset by the considerable benefit.", "nan", "The aim of the study was to test the value of low dose aspirin associated with standard oral anticoagulants (OAC) after mechanical mitral valve replacement (MMRV) to reduce strands, thrombi and thromboembolic events.\n Strands and thrombi are thought to increase the risk of embolic events after MMVR, particularly in the immediate postoperative period.\n Two hundred twenty-nine patients were prospectively recruited: 109 patients (group A+) were randomly assigned to aspirin (200 mg per day) with OAC and 120 patients (group A-) to OAC alone (international normalized ratio 2.5 to 3.5). All patients were subjected to multiplane transesophageal echocardiography at nine days and five months and were followed up for one year.\n At nine days and five months, there was a high and comparable incidence of strands in the two groups (group A+: 44%, 58%; group A-: 49%, 63%). However, the incidence of nonobstructive periprosthetic valve thrombi was significantly lower in group A+ at 9 days: 5% versus 13%, p = 0.03. Total thromboembolic events were reduced in group A+ (9% vs. 25%, p = 0.004) although there was an increased incidence of gastrointestinal hemorrhage (7% vs. 0%). Overall mortality was 9% in group A+ and 4% in group A-. Valve-related events were similar in both groups. Early thrombi, but not strands, were associated with higher morbidity, especially thromboembolic events (30% vs. 13%, p = 0.003).\n One year after MMVR, the association of aspirin with OAC reduced thrombi and thromboembolic events, but not morbidity, due to an increase in hemorrhagic complications.", "Mechanical heart valve replacement requires lifelong anticoagulant treatment. Aspirin has proved useful in further reducing thromboembolic events when added to oral anticoagulants. However, increased (gastrointestinal) bleeding was observed at the doses previously tested for this combination in heart valve prostheses.\n We performed a prospective randomized trial to compare the combination of low-intensity oral anticoagulants (international normalized ratio 2.5 to 3.5) plus aspirin (100 mg/day) (arm A) versus high-intensity oral anticoagulants alone (arm B) (international normalized ratio 3.5 to 4.5). Arm A included 258 patients and arm B 245 patients. The two groups were comparable for all baseline characteristics.\n The outcomes of the study were embolism, valve thrombosis, and major hemorrhage. The median follow-up was 23 months. The two treatments offered similar antithrombotic protection. The incidence of embolic episodes was 1.32 per 100 patient-years (95% confidence interval 0.53 to 2.7) for arm A and 1.48 per 100 patient-years (95% confidence interval 0.59 to 3.03) for arm B. Major hemorrhage occurred in 1.13 per 100 patient-years (95% confidence interval 0.41 to 2.45) for arm A and 2.33 per 100 patient-years (95% confidence interval 1.17 to 4.14) for arm B. Gastrointestinal bleeding was not increased by this combined reduced dose of aspirin and coumarin.", "Prevention of arterial thromboembolism with acetylsalicylic acid (ASA) was studied in 148 patients with single Starr-Edwards aortic ball-valve prostheses. These patients are suitable for such a study because they have a high incidence of arterial emboli derived mainly from thrombi formed on the valves. They were given either 1 Gm. of ASA daily or placebo in combination with anticoagulants, and were observed for 2 years. Only two emboli occurred in patients receiving ASA, none of them severe. In the placebo group 12 thromboembolic episodes were diagnosed in 10 patients, and three with cerebral emboli died; in one a subdural hematoma unrelated to the embolus was found. In addition, one fatal and the one nonfatal intracranial bleeding occurred in each group, whereas gastrointestinal complications were seen more frequently in patients taking ASA. It is concluded that ASA combined with anticoagulants offered a significantly better protection against arterial thromboembolism than did anticoagulant therapy alone.", "nan" ]

[ "4004696", "7673534", "9337501", "1460157", "4710043", "2030245" ]

[ "Group versus individual applications of reciprocity training for parent-youth conflict.", "Multisystemic treatment of serious juvenile offenders: long-term prevention of criminality and violence.", "Multisystemic therapy with violent and chronic juvenile offenders and their families: the role of treatment fidelity in successful dissemination.", "Family preservation using multisystemic therapy: an effective alternative to incarcerating serious juvenile offenders.", "Short-term behavioral intervention with delinquent families: impact on family process and recidivism.", "A comparative evaluation of parent-training interventions for families of chronic delinquents." ]

[ "nan", "This article examined the long-term effects of multisystemic therapy (MST) vs. individual therapy (IT) on the prevention of criminal behavior and violent offending among 176 juvenile offenders at high risk for committing additional serious crimes. Results from multiagent, multimethod assessment batteries conducted before and after treatment showed that MST was more effective than IT in improving key family correlates of antisocial behavior and in ameliorating adjustment problems in individual family members. Moreover, results from a 4-year follow-up of rearrest data showed that MST was more effective than IT in preventing future criminal behavior, including violent offending. The implications of such findings for the design of violence prevention programs are discussed.", "The effects of multisystemic therapy (MST) in treating violent and chronic juvenile offenders and their families in the absence of ongoing treatment fidelity checks were examined. Across 2 public sector mental health sites, 155 youths and their families were randomly assigned to MST versus usual juvenile justice services. Although MST improved adolescent symptomology at posttreatment and decreased incarceration by 47% at a 1.7-year follow-up, findings for decreased criminal activity were not as favorable as observed on other recent trials of MST. Analyses of parent, adolescent, and therapist reports of MST treatment adherence, however, indicated that outcomes were substantially better in cases where treatment adherence ratings were high. These results highlight the importance of maintaining treatment fidelity when disseminating complex family-based services to community settings.", "Multisystemic therapy (MST) delivered through a community mental health center was compared with usual services delivered by a Department of Youth Services in the treatment of 84 serious juvenile offenders and their multiproblem families. Offenders were assigned randomly to treatment conditions. Pretreatment and posttreatment assessment batteries evaluating family relations, peer relations, symptomatology, social competence, and self-reported delinquency were completed by the youth and a parent, and archival records were searched at 59 weeks postreferral to obtain data on rearrest and incarceration. In comparison with youths who received usual services, youths who received MST had fewer arrests and self-reported offenses and spent an average of 10 fewer weeks incarcerated. In addition, families in the MST condition reported increased family cohesion and decreased youth aggression in peer relations. The relative effectiveness of MST was neither moderated by demographic characteristics nor mediated by psychosocial variables.", "nan", "Fifty-five families of chronically offending delinquents were randomly assigned to parent-training treatment or to service traditionally provided by the juvenile court and community. The families in the parent-training group received an average of 44.8 hours of professional contact (23.3 hours of which were phone contacts), and each control group family received treatment estimated at more than 50 hours on the average. Comparisons of police contact data at baseline and subsequent years for the two groups showed that subjects in both groups demonstrated reduced rates of offending during the followup years. The finding most relevant was significant treatment-by-time effect for offense rates, with most of this effect accounted for by a greater reduction in serious crimes for the experimental group during the treatment year, and a similar reduction of the community control group occurring in the first of three followup years. These early decrements in offense rates persisted during followup for both groups. Throughout the study, boys in the experimental group spent significantly less time in institutional settings than did boys in the control group. Parent training had a significant impact, but the reduction in offending was produced at very high emotional cost to staff. Although it is clear that this population requires substantial treatment resources, this study underscores the need for more work on prevention." ]

[ "12269458", "285752", "321181", "6337712", "6399218", "2403486", "4150790", "1055598", "14204414", "6754242", "4400046", "4381422", "279409", "9372795", "7004469", "6365424", "359013", "3288434", "6943157", "369697", "4154819", "12202647", "3476523", "15528909", "6088166", "14283021", "4147760", "4401615", "271002", "4386355", "18042987", "3060308", "4395021", "4400318", "7005653", "270395", "6342787", "4394685", "11553111", "4295135", "224083", "3469030", "4148037", "6253112", "13270998", "4380623", "399995", "170634", "7960166", "4396165", "2691402", "6572128", "19278083", "4389702", "295120", "6589669", "9835826", "3290299", "356989", "9017171", "7960167" ]

[ "A randomised controlled trial of the effectiveness of providing free fluoride toothpaste from the age of 12 months on reducing caries in 5-6 year old children.", "A supervised brushing trial of sodium monofluorophosphate dentifrices in a fluoridated area.", "A 3-year clinical trial of the effect on dental caries of a dentifrice containing 2% sodium monoflurophosphate.", "The effects of changing caries prevalence and diagnostic criteria on clinical caries trials.", "Relative efficacy of dentifrices containing 250 or 1000 ppm F- in preventing dental caries--report of a 32-month clinical trial.", "Caries-preventive effect of fluoride dentifrices with and without anticalculus agents: a 3-year controlled clinical trial.", "Caries-inhibition by an amine fluoride dentifrice results after 6 years in children with low caries activity.", "A dentifrice containing 0.8 per cent sodium monofluorophosphatein an aluminium oxide trihydrate base. A 3-year clinical trial.", "A PRELIMINARY COMPARISON OF A DENTIFRICE CONTAINING FLUORIDE AND SOLUBLE PHOSPHATE AND EMPLOYING A CALCIUM-FREE ABRASIVE WITH OTHER TYPES OF FLUORIDE DENTIFRICES. FIRST YEAR REPORT OF A CLINICAL STUDY.", "Comparative unsupervised clinical trial on caries inhibition effect of monofluorophosphate and amine fluoride dentifrices after 3 years in Strasbourg, France.", "A multiple-examiner clinical evaluation of a sodium fluoride dentifrice.", "[Clinical experimentation with a fluoridated dentifrice].", "A clinical trial of a calcium carbonate base dentifrice containing 0.76% sodium monofluorophosphate.", "A three-year clinical trial of a combination of trimetaphosphate and sodium fluoride in silica toothpastes.", "Caries prevention by dentifrices containing a combination of sodium monofluorophosphate and sodium fluoride. Report of a 3-year clinical trial.", "Caries prevention using a 1.2% sodium monofluorophosphate dentifrice in an aluminium oxide trihydrate base.", "Caries prevention by daily supervised use of a MFP gel dentifrice. Report of a 3-year clinical trial.", "A 3-year clinical trial to compare efficacy of dentifrices containing 1.14% and 0.76% sodium monofluorophosphate.", "Effect of stannous fluoride treatments on the progression of initial lesions in approximal surfaces of permanent posterior teeth.", "A 3-year clinical trial of calcium carbonate dentifrice containing calcium glycerophosphate and sodium monofluorophosphate.", "Studies on the effect of dentifrices with low fluoride content.", "An abbreviated caries clinical trial design validated over 24 months.", "A three-year clinical comparison of a sodium monofluorophosphate dentifrice with sodium fluoride dentifrices on dental caries in children.", "The relative anticaries effectiveness of three fluoride-containing dentifrices in Puerto Rico.", "Caries inhibition of a dentifrice containing 0.78% sodium monofluorophosphate in a silica base.", "EVALUATION OF A STANNOUS FLUORIDE-CALCIUM PYROPHOSPHATE DENTIFRICE.", "A clinical evaluation of a stannous fluoride and a sarcosinate dentifrice.", "Clinical evaluation of an aged stannous fluoride-calcium pyrophosphate dentifrice.", "Clinical testing of a mouthrinse and a dentifrice containing fluoride. A two-year supervised study in school children.", "Some statistical aspects of a clinical study on dental caries in children.", "Low-fluoride dentifrice and caries lesion control in children with different caries experience: a randomized clinical trial.", "A 3-year oral health dose-response study of sodium monofluorophosphate dentifrices with and without zinc citrate: anti-caries results.", "The effect of a fluoride gel used for supervised toothbrushing 15 or 30 times per year.", "Clinical evaluation of neutral sodium fluoride, stannous fluoride, sodium monofluorophosphate and acidulated fluoride-phosphate denifrices.", "[Cariostatic effect of Fluocaril; controlled clinical research].", "[Caries prevention by means of a Na2FPO3-toothpaste after 7 year's application].", "A four-year clinical study to determine the caries-inhibiting effect of calcium glycerophosphate and sodium fluoride in calcium carbonate base dentifrices containing sodium monofluorophosphate.", "A clinical comparison of fluoride and antienzyme dentifrices.", "Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year.", "Cariostatic effect of a stannous fluoride-containing dentifrice on children: two-year report of a supervised toothbrushing study.", "The relative caries-inhibiting effects of a stannous fluoride dentifrice in a silica gel base.", "Clinical comparison of the caries inhibition of two mixed NaF-Na2PO3F dentifrices containing 1,000 and 2,500 ppm F compared to a conventional Na2PO3F dentifrice containing 1,000 ppm F: results after two years.", "Clinical evaluation of three concentrations of sodium fluoride in dentifrices.", "Caries-inhibiting effect of a stannous fluoride silica gel dentifrice: a three-year clinical study.", "A comparison between the anticariogenic effects of dentifrices containing stannous fluoride and sodium fluoride.", "Effect of SnF2 dentrifices on caries in children: two-year clinical study of supervised brushing in children's homes.", "[Controlled clinical study of the caries prophylactic activity of a new bifluoride toothpaste (sodium monofluorophosphate + sodium fluoride)].", "A clinical evaluation of a sodium fluoride dentifrice.", "Results from a three-year caries clinical trial comparing NaF and SMFP fluoride formulations.", "Clinical testing of fluoride and non-fluoride containing dentifrices inHounslow school children.", "Clinical trial of a low-fluoride toothpaste for young children.", "Combined effects of a fluoride dentifrice and mouthrinse on the incidence of dental caries.", "Clinical investigation of the anticaries efficacy of a 1.14% sodium monofluorophosphate (SMFP) calcium carbonate-based dentifrice: a two-year caries clinical trial on children in China.", "Stannous fluoride and sodium monofluorophosphate dentifrices. Clinical testing in London school children--radiological findings.", "Results of gingival, plaque, and stain assessments after 30 months use of amine fluorides and their inorganic counterparts.", "[3-year clinical tooth cream test with toothpastes of varying fluoride content: 0.8% and 1.2% sodium monofluorophosphate].", "Reversal of incipient and radiographic caries through the use of sodium and stannous fluoride dentifrices in a clinical trial.", "A clinical investigation of a high-level fluoride dentifrice.", "A three-year clinical study to determine the separate and combined caries-inhibiting effects of sodium monofluorophosphate toothpaste and an acidulated phosphate-fluoride gel.", "Effect of supervised use of an alum mouthrinse on dental caries incidence in caries-susceptible children: a pilot study.", "The effect of NaF and SMFP toothpastes on three-year caries increments in adolescents." ]

[ "To assess the impact of regularly supplying free fluoride toothpaste regularly to children, initially aged 12 months, and living in deprived areas of the north west of England on the level of caries in the deciduous dentition at 5-6 years of age. A further aim was to compare the effectiveness of a programme using a toothpaste containing 440 ppmF (Colgate 0-6 Gel) with one containing 1,450 ppmF (Colgate Great Regular Flavour) in reducing caries.\n Randomised controlled parallel group clinical trial. Clinical data were collected from test and control groups when the children were 5-6 years old.\n A programme of posting toothpaste with dental health messages to the homes of children initially aged 12 months. Clinical examinations took place in primary schools.\n 7,422 children born in 3-month birth cohorts living in high caries areas in nine health districts in north west England. Within each district children were randomly assigned to test or control groups.\n Toothpaste, containing either 440 ppmF or 1450 ppmF, and dental health literature posted at three monthly intervals to children in test groups until they were aged 5-6 years.\n The dmft index, missing teeth and the prevalence of caries experience.\n An analysis of 3,731 children who were examined and remained in the programme showed the mean dmft to be 2.15 for the group who had received 1,450 ppmF toothpaste and 2.49 for the 440 ppmF group. The mean dmft for the control group was 2.57. This 16% reduction between the 1,450 ppmF and control group was statistically significant (P<0.05). The difference between the 440 ppmF group and control was not significant. Further analyses to estimate the population effect of the programme also confirmed this relationship.\n This study demonstrates that a programme distributing free toothpaste containing 1,450 ppmF provides a significant clinical benefit for high caries risk children living in deprived, non-fluoridated districts.", "nan", "A clinical trial of a dentifrice containing 2% sodium monofluorophosphate was carried out on 782 schoolchildren in Shropshire, England. After 3 years, a reduction of 23.8% was found in the DMFS increment obtained from clinical examination. The reduction was 38.8% using radiographs. The children were divided into three groups according to baseline DMFS. Those with a \"medium\" caries experience were found to benefit most from using the dentifrice. There was a difference in the effect on individual tooth sites; the approximal surfaces of the posterior teeth received the most benefit and the occlusal surfaces the least.", "nan", "nan", "A 3-year, double-blind, randomized caries trial was conducted to evaluate the relative anticaries efficacy of four sodium fluoride dentifrices containing 250 ppm fluoride, 1,000 ppm fluoride in combination with 1% disodium 1-hydroxyethylidene-1.1-bisphosphonate (HEBP), and 1,000 ppm fluoride in combination with 1% disodium azacycloheptylidene-2.2-bisphosphonate (AHBP). As a positive control, a monofluorophosphate dentifrice (1,000 ppm fluoride) was used. At outset 1,161 Icelandic children, 11 and 12 years of age, were randomly assigned to one of the five treatment groups and 1,035 subjects completed the trial. After 3 years of unsupervised brushing, the dentifrice containing 250 ppm fluoride was significantly less effective in controlling the caries increment. The combination of sodium fluoride and AHBP was significantly more effective than the positive control.", "nan", "nan", "nan", "A randomized, double blind clinical trial of the caries inhibition effects of dentifrices containing respectively monofluorophosphate and amine fluoride was performed. A third control group used a toothpaste without fluoride. A total number of 2008 schoolchildren ranging in age from 6 to 8 years and living in Strasbourg (France) participated in this study. After a baseline examination three groups were constructed with the block randomization technic. The caries inhibition effects of the three dental pastes were compared after 3 years of unsupervised use. The monofluorophosphate dentifrice showed a reduction of 7.02% for DMFT, 5.17% for DMFS and 25.26% for the df rate. The reduction of amine fluoride dentifrice caries was respectively 21.62% for DMFT, 20.94% for DMFS and 48.66% for the df rate.", "nan", "nan", "nan", "The relative efficacy of NaF silica toothpastes containing 1000 ppm fluoride and 1500 ppm fluoride in the control of dental caries is not clear-cut. Also, it has not been established that incorporation of trimetaphosphate (TMP) improves the anticaries activity of NaF toothpastes. A three-year clinical trial was conducted to test the hypotheses that: (i) the anticaries activity of NaF toothpastes containing 1500 ppm F was greater than that of NaF toothpastes containing 1000 ppm F, and (ii) inclusion of TMP improved the efficacy of NaF silica pastes. Subsidiary aims included determination of whether frequency of toothbrushing and method of rinsing after brushing were correlated with caries increments. The study involved 4196 children aged 11 to 12 years at outset. These participants had been selected from a pool of 7374 potential subjects on the basis of caries experience and dental eruption pattern. They were stratified by sex, examiner, and presence of calculus and caries, and were allocated at random to one of the four toothpastes under study. Using mirror and probe and also FOTI, we carried out clinical examinations at baseline and annually thereafter for 3 yrs. Bitewing radiographs of a subset of children were taken at baseline and at the end of the study. The outcome measure for the study, DMFS increment, was defined as the increase in caries over 3 yrs, taking into account changes occurring on individual tooth surfaces. Data for 3467 subjects were available for analyses at both baseline and year 3 examinations. Radiographs were taken for 1942 subjects at both baseline and year 3 examinations. The mean three-year clinical-only DMFS increment for the subjects using 1500-ppm-NaF pastes was 3.93, which was 6% lower than the corresponding mean of 4.19 for the 1000-ppm-NaF pastes. There was no significant difference between the mean DMFS increment for those using paste with or without TMP. Subjects who claimed to brush more frequently or who claimed not to use a tumbler to rinse after toothbrushing had lower three-year DFMS increments.", "nan", "A 3-year clinical trial was carried out in France just after fluoride toothpaste was allowed to be sold on the mass market. The aim was to assess the caries preventive effect of a toothpaste containing the maximum fluoride level permitted by the EEC (1.2% SMFP). The trial started with 1318 10-12-yr-old children from a wide socioeconomic background in a typical French community. Test toothpaste was given to 659 children whereas the remaining 659 children obtained the same toothpaste without the fluoride additive. The brushing was unsupervised and performed by the children at home. Dental caries was assessed by clinical and radiographic examinations. 1061 children completed the trial. An interview carried out at the final examination identified a group of 116 uncooperative children (less than five brushings a week on average) who were not included in the statistical analysis. The following mean reductions were found: 26% for DMFT, 27% for DMFS, and 39% for DMFSU. The DMFS index for approximal, buccal-lingual and occlusal surfaces showed caries reductions of 32%, 25%, and 22%, respectively. The trial demonstrated a highly significant effectiveness of the 1.2% SMFP toothpaste in a French population.", "nan", "A 3-yr daily supervised toothbrushing study with a double blind design was conducted to evaluate the anticaries effectiveness of a 1.14% sodium monofluorophosphate (MFP) dentifrice (1500 ppm F) compared to a 0.76% MFP dentifrice (1000 ppm F). This study began with nearly 4000 children, primarily aged 8-11, in grades 3-5, residing in a nonfluoridated community in Florida. A total of 2415 children completed 3 yr of the study, representing 61% of the children who began the study. The results indicate a statistically significant (P less than 0.001) anticaries benefit was derived over a 3-yr period from the use of the higher fluoride dentifrice (1500 ppm F) when compared to the positive control (1000 ppm F). Percent reductions in mean dental caries increments were 20.9%, 22.1%, 21.8%, 24.3%, and 35.2% for DMFT, DFT, DMFS, DFS, and DFS Interproximal, respectively.", "Bite-wing radiographs were used to determine the effect of three forms of topical SnF2 therapy on the progression of initial lesions in the approximal surfaces of permanent posterior teeth. Radiographs were taken annually over a four-year period. The subjects were schoolchildren, aged 12-14 yr, living in a low fluoride area. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, had no discernible effect on the development of the initial lesions. However, the home use of a SnF2 dentifrice did inhibit caries progression appreciably at all but one of the four time intervals in the study. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, combined with the home use of a SnF2 dentifrice, was the most effective treatment in retarding lesion development. Even without topical fluoride therapy, the rate of progression of initial approximal lesions was generally quite slow. In view of these findings, it would seem sound clinical practice to treat all initial lesions in approximal surfaces with topical fluoride therapy and delay placement of restorations until there is radiographic evidence of lesions reaching dentin.", "nan", "nan", "Conventional caries trials last from 24 to 36 months. This study evaluated whether the previously established difference in efficacy between 1000- and 2500-ppm-fluoride dentifrices could be detected after 12 months. Caries was assessed by clinical visual assessment (CVA-simplified version of Dundee Selectable Threshold Method - DSTM), bitewing radiography, and Fiber Optic Transillumination (FOTI). Changes in status for individual surfaces were classified by means of pre-prepared matrices as 0 (unchanged), +1 (initiation or progression), or -1 (regression) and summed for each subject to yield an event score. Mean group event scores were calculated for each product. DSTM at the D(1) [enamel and dentin] threshold showed significant inter-group differences in mean event scores (p < 0.003) and D(1)MFS increment (< 0.007) at 12 months; these were confirmed at 24 months by traditional increment analysis (CVA & FOTI at the D(3) (dentin only) threshold + radiography, p < 0.03). This study confirms the validity of an abbreviated trial protocol.", "This study compared the anticaries effects of these three fluoride-containing dentifrices: 1100 ppm F as NaF (positive control); 2800 ppm F as SMFP; and 2800 ppm F as NaF. The group using the 2800 SMFP dentifrice showed no significant differences in DMFS or DMFT, compared to the positive control, at anytime during the study. This indicated that higher levels of sodium monofluorophosphate in a dentifrice offer no advantage in caries protection over the conventional level of sodium fluoride, 1100 ppm F.", "The objective of this research was to evaluate the anticaries effectiveness of a low-dose (500 ppm F, low-NaF) sodium fluoride dentifrice, a high-dose (2,800 ppm F, high-NaF) sodium fluoride dentifrice and an experimental 0.454% stabilized stannous fluoride (1,100 ppm F) with sodium hexametaphosphate (SnF2-HMP) dentifrice, each relative to a standard 1,100 ppm F sodium fluoride positive control dentifrice. Subjects (n = 955, with approximately 239 per group) with a mean age of 10.6 (approximately 9-12 years) were randomly assigned to one of four dentifrice treatments. Two calibrated examiners independently measured visual-tactile caries as DMFS that was supplemented with a radiographic examination at baseline, 12 months and 24 months for each subject. Generally similar results were independently observed by both examiners at the conclusion of the 2-year study period. Considering all subjects that attended at least 60% of the supervised brushing sessions, statistically significantly less caries was observed in the high-NaF group compared to the control group. Similarly, statistically significantly less caries was observed in the SnF2-HMP group as compared to the control group. Differences in caries increments between the low-NaF and control groups were not statistically significant. One of the examiners observed these same statistically significant differences after 1 year. In conclusion, the results of this clinical trial indicated that while no difference in caries increments was observed between the low-NaF and control groups, both the high-NaF and the SnF2-HMP groups experienced significantly fewer lesions than the control group.\n 2004 S. Karger AG, Basel.", "The purpose of this double blind clinical trial was to determine the anticaries activity of a dentifrice containing 0.78% sodium monofluorophosphate in a silica gel abrasive base compared with a placebo under conditions of supervised brushing. 1154 schoolchildren, ages 9-12, were recruited in a non-fluoridated semi-rural area of northeastern Connecticut. Subjects were stratified according to school, grade and sex, and then randomly divided into two groups. Each school day, children brushed their teeth for 1 min under supervision by project personnel. Weekend and vacation usage was ad libitum. Caries examinations and radiographic readings were performed by the same examiner (J.R.). After 12 months, the 996 subjects examined showed that the group using the test dentifrice had significantly (less than 0.05) lower DMFT (25.0%) and DMFS (19.1%) increments than the group using the placebo. After 24 months the 876 subjects examined showed that the test group continued to have significantly lower DMFT (24.5%) and DMFS (24.7%) increments than the placebo group. Surface protection after 24 months ranged from 22.1% for occlusal to 37.1% for interproximal surfaces.", "nan", "nan", "nan", "nan", "nan", "Since there is no consensus on the anticaries effectiveness of low-fluoride (F) dentifrice, this randomized clinical trial evaluated its effect in children at different caries activity status. One hundred and twenty 2- to 4-year-old children, half with and half without active caries lesions, were randomly divided into 2 groups which used 500- or 1,100-microg F/g (NaF) dentifrices during 1 year. Caries progression or regression were evaluated as the number of lesions becoming active/cavities or inactive, respectively. The anticaries effect of the low-F dentifrice was similar to the conventional F dentifrice when used by caries-inactive children. However, in children with active caries lesions the low-F dentifrice was less effective than the 1,100-microg F/g dentifrice in controlling the progression of lesions. The data suggest that the child caries activity may be taken into account to recommend a low-F dentifrice.", "A 3-yr clinical trial has been conducted on 3000 12-yr-old children in Lanarkshire, Scotland, with the aim of investigating the effects on oral health of toothpastes containing both sodium monofluorophosphate and zinc citrate, the former being present at fluoride levels of 1000, 1500, and 2500 ppm F. No significant difference in caries increments was found between the group of children using toothpastes incorporating zinc citrate and their counterparts using zinc-free pastes. However, a significant anti-caries dose-response was demonstrated over the SMFP range used. This dose-response was evident for boys and girls and also for the various types of teeth and tooth surfaces.", "nan", "nan", "A controlled, double-blind trial on 42 children showed that a dentrifrice containing 0,25% fluorine clearly prevented caries when used continuously for 2 years. This effects was greater than that of a similar toothpaste containing fluorine. Tolerance was excellent.", "After 7 years unsupervised use of a Na2FPO3 paste the number of new DMF-surfaces was 36 to 38% lower than in the control group. The caries-inhibiting effect is statistically significant (P less than 0.001). Separate consideration of the first molar reduced caries of the other teeth to 40--42%.", "nan", "nan", "There is limited evidence from clinical trials on the dose response of sodium fluoride dentifrices at concentrations above 1100 ppm fluoride ion, with respect to caries efficacy. This randomized, double-blind study examined the anti-caries effectiveness of sodium fluoride dentifrices containing 1700 ppm, 2200 ppm and 2800 ppm fluoride ion relative to an 1100 ppm fluoride ion control. A population of 5439 elementary schoolchildren, aged 6-15 years, was recruited from an urban central Ohio area with a low fluoride content water supply (<0.3 ppm). Subjects were examined by visual-tactile and radiographic examination at baseline and after 1, 2, and 3 years of using the sodium fluoride dentifrices. Subjects were stratified according to gender, age and baseline DMFS scores derived from the visual-tactile baseline examination and randomly assigned to one of four treatment groups: 0.243% sodium fluoride (1100 ppm fluoride ion), 0.376% sodium fluoride (1700 ppm fluoride ion), 0.486% sodium fluoride (2200 ppm fluoride ion), and 0.619% sodium fluoride (2800 ppm fluoride ion). All products were formulated with the same fluoride compatible silica abrasive. Results after 1 year provided evidence of a positive sodium fluoride dose response. Compared to the 1100 ppm fluoride treatment group, the 1700 ppm fluoride treatment group had an 11.0% reduction in DMFS that was not statistically significant, while the 2200 ppm and 2800 ppm fluoride treatment groups showed statistically significant (P<0.05) reductions of 18.6% and 20.4%, respectively. The reductions in caries delivered by the higher fluoride dentifrices were present across all tooth surface types, but were most pronounced for occlusal surfaces. Results at years 2 and 3 were confounded by a concurrent fluoride rinse program, which involved portions of the study population. While the trends for the higher fluoride dentifrices observed at year 1 remained at years 2 and 3, the difference observed between treatments were substantially less and failed to reach statistical significance (P<0.05). Collectively, the data demonstrate that the 2200 ppm and the 2800 ppm fluoride treatments delivered statistically significantly greater caries efficacy than the 1100 ppm fluoride treatment. This large-scale clinical trial provides evidence of a positive statistically significant dose relationship between dental caries and sodium fluoride in a dentifrice at levels above 1100 ppm fluoride at year 1.", "nan", "An unsupervised toothbrushing study involving 1,339 children from 5 to 13 years of age conducted for three years compared two stannous fluoride dentifrices, one in a calcium pyrophosphate base and the other in a silica gel base, with a nonfluoride control dentifrice. The test dentifrice, stannous fluoride in a silica gel base, reduced caries to a significant extent when compared with the nonfluoride control dentifrice.The percentage of reductions ranged from 15% to 25% for whole mouth and interproximal surface indexes. There was no significant difference between the two fluoride dentifrices.", "nan", "nan", "nan", "nan", "nan", "nan", "A double-blind study to determine the anticaries efficacy of a neutral pH dentifrice containing sodium fluoride and a high Beta-phase calcium pyrophosphate was conducted among elementary school children in Kansas City, Missouri. A sample of 567 children ages 8-13 were recruited and randomly assigned to test and control groups: the test group received a sodium fluoride high Beta-phase calcium pyrophosphate dentifrice, and the control group received a calcium pyrophosphate dentifrice without the active ingredient. The sodium fluoride dentifrice contained fluoride at the level of 1000 ppm. Caried examinations were conducted at initiation, after 12 months, and again after 24 months at the study's termination. All examinations (clinical and radiographic) were performed by the same investigator. At 12 months the sodium fluoride dentifrice demonstrated a caries reduction of 24.1% (DMFS). At 24 months the reduction demonstrated was 30.1% (DMFS); this reduction is significant at alpha = 0.05.", "A three-year, double blind, randomised clinical trial was conducted in Polk County, Florida from 1983-1987. The objective was to compare the effect of four dose levels of sodium monofluorophosphate (SMFP) and a single dose level of sodium fluoride (NaF) on DMFS, DMFT, and DFS Interproximal indices. A total of 8,027 children were examined clinically and radiographically at baseline, and 5,474 children completed the three-year study, which included daily supervised brushing at school. No differences existed at baseline between the five study cells on age or gender distribution, or on any of the dental indices. Results indicated that the 2000 ppm F NaF group had significantly smaller DMFS increment than the 2000 ppm F SMFP group p < 0.005. The 2000 ppm F NaF group demonstrated an 18 per cent (26 per cent for children > 10 years at baseline) reduction in DMFS over the 1500 ppm F SMFP group, the 2500 ppm F group a 15 per cent (19 per cent) reduction, and the 2000 ppm F SMFP a 5 per cent (9 per cent) reduction. Results are strongest in children at greatest risk--older children with previous caries. This study concludes that the anticaries efficacy of SMFP dentifrices rises with increasing fluoride, and that the anticaries efficacy of a 2000 ppm NaF dentifrice is superior to that of a 2000 ppm F SMFP dentifrice, p < 0.005).", "nan", "In this double-blind trial, the anticaries effectiveness of a test toothpaste formulated for young children with 550 ppm F was compared with that of a positive control toothpaste containing 1055 ppm fluoride. More than 3000 2-year-old children were enrolled in the study and after 3 years of toothpaste use, 2177 (72 per cent) were examined. From a clinical and radiographic assessment, more than half the children were found to be caries free and only 32 (1.5 per cent) had evidence of rampant caries. There appeared to be little or no difference between children who had used test or control pastes, either in caries or in plaque levels. On the basis of this clinical trial the experimental toothpaste with 550 ppm fluoride would appear to have a similar anticaries efficacy to that of the control toothpaste. Differences were seen in relation to sex of the child and to social class. Girls had lower levels of plaque than boys but more carious teeth. Children from families in higher social classes had fewer carious teeth and lower levels of plaque.", "751 14- and 15-year old children completed a 3-year, double-blind, caries preventive program. The effects of daily, supervised toothbrushing with an 0.76% sodium monofluorophosphate dentifrice, rinsing with a 0.05% sodium fluoride mouthrinse, and the combined effects of the two treatments were investigated. Both the dentifrice and mouthrinse reduced the incidence of dental caries, but their combined use at the same time had no greater effect than either used alone.", "The objective of this two-year comparative investigation was to assess the anticaries efficacy of three dentifrices commercially available in China. Two products contained the stated active agent sodium monofluorophosphate (SMFP) at a concentration of 1.14%; one was calcium carbonate-based, the second was silica-based. The third dentifrice tested contained no fluoride and was calcium carbonate-based.\n Prior to the start of this double-blind, parallel-group study, all aspects of the study were reviewed and approved by the human review committee of the West China College of Stomatology, Sichuan University. All parents signed the approved consent form before the initial evaluations. A total of 1200 qualifying children living in the Chengdu, China area entered the study, and 998 children completed all aspects of the study. Subjects were randomly assigned to use one of the three dentifrices: 328 participants used the non-fluoride calcium carbonate-based dentifrice; 341 participants used the 1.14% SMFP silica-based dentifrice; and 329 participants used the 1.14% SMFP calcium carbonate-based dentifrice. Participants were instructed to brush their teeth with their assigned dentifrice twice daily. Brushing instructions were reinforced.\n At the baseline examination, the mean dfs (decayed and filled tooth surfaces) scores of the non-fluoride dentifrice group (3.60 +/- 6.07),the 1.14% SMFP silica-based dentifrice group (3.53 +/- 5.62), and the 1.14% SMFP calcium carbonate-based dentifrice group (3.54 +/- 5.34) were not statistically different (p > 0.05). After one year, the mean dfs increment of the non-fluoride dentifrice group was 2.19 +/- 4.12, 1.69 +/- 3.12 for the 1.14% for the SMFP silica-based dentifrice group, and 1.53 +/- 3.09 for the 1.14% SMFP calcium carbonate-based dentifrice group; after two years, the mean dfs increments were 4.73 +/- 5.17, 2.98 +/- 4.42, and 2.75 +/- 4.33, respectively. Both the 1.14% SMFP calcium carbonate-based and the 1.14% SMFP silica-based dentifrices provided significantly more caries reduction than the non-fluoride silica-based dentifrice after one year (-30% and -23%) and two years (-42% and -37%) of product use. The 1.14% SMFP calcium carbonate-based dentifrice was not significantly different from the 1.14% SMFP silica-based dentifrice after one and two years of use.\n The results of this clinical study indicate that the 1.14% SMFP calcium carbonate-based and the 1.14% SMFP silica-based dentifrices are effective against tooth decay compared to brushing with a non-fluoride toothpaste.", "nan", "nan", "nan", "Experimental evidence has clearly demonstrated that the early stages of lesion formation (enamel demineralization) are reversible following exposure to saliva and/or fluoride. Clinical evidence for remineralization has also been reported extensively in the literature. However, the literature is lacking with respect to data from well-controlled clinical studies regarding the quantitative contribution of remineralization to arrestment and reversal of caries. Retrospective analysis of an existing clinical trial database provided an opportunity to examine the incidence of clinical lesion reversals in a placebo-controlled, double-blinded caries clinical study. The clinical study examined three treatment groups: 1) 0.243% sodium fluoride/silica dentifrice, 2) 0.4% stannous fluoride/calcium pyrophosphate (positive control) dentifrice and 3) non-fluoridated placebo/calcium pyrophosphate (negative control) dentifrice. Clinical measures in this study included both radiographic and visual-tactile assessments of caries. Examination of all subjects revealed a statistically greater frequency for caries reversals in the sodium fluoride group as compared to the placebo group at Year 3, for both total and radiographic caries. In contrast, while caries reversals in the stannous fluoride group occurred with greater frequency than in the placebo group at Year 3, for both total and radiographic caries, the differences were not statistically significant. When only subjects who were \"at risk\" for potential reversals (i.e., those with a minimum of one carious lesion at baseline) were examined, a statistically greater frequency in caries reversals was observed in both the sodium fluoride (total, incipient, and radiographic caries) and stannous fluoride (total and radiographic caries) groups as compared to the placebo group at Year 3. Collectively, these data confirm the ability of both 0.243% sodium fluoride/silica and 0.4% stannous fluoride/calcium pyrophosphate dentifrices to clinically reverse caries. The results suggest that sodium fluoride may deliver a greater frequency of caries reversals than stannous fluoride, although these treatments were not found to be significantly different.", "nan", "nan", "Aluminum salts have demonstrated anticaries activity in a number of laboratory and animal studies. The aim of this double-blind, pilot, clinical trial was to evaluate the effect of an alum (Al) mouthrinse on dental caries formation both by itself and in combination with an ADA-approved sodium fluoride (F) dentifrice. A total of 260 caries-prone children residing in a low-F area were preselected for the study and scored independently for caries by two experienced examiners. After using gender, age, and initial DMFT(S) scores for baseline stratification, the subjects were assigned to one of three treatment regimens: (1) placebo mouthrinse and F dentifrice, (2) Al mouthrinse and placebo dentifrice, and (3) Al mouthrinse and F dentifrice. The alum mouthrinse contained 500 ppm Al and the sodium fluoride dentifrice contained 1100 ppm F. Rinsing was supervised at school on weekdays for 30 sec/day, while the dentifrices were used ad libitum at home. Subjects were reexamined for caries and oral health after six and twelve months. Both examiners found that children who used Al mouthrinse, in conjunction with either placebo or F dentifrices, had lower caries incidence than those who used placebo mouthrinse/F dentifrice combination; but the differences were statistically significant for only one of the examiners. No evidence of deleterious effects to the oral tissues was observed. The results of this pilot clinical trial demonstrated that daily supervised use of an alum mouthrinse inhibited caries development in decay-prone children at least as effectively as a F dentifrice.", "A three-year double blind clinical caries trial was undertaken to compare the anticaries efficacy of three types of active agent, namely sodium fluoride (NaF), sodium monofluorophosphate (SMFP) and the combination of NaF plus sodium trimetaphosphate (TMP), using two fluoride levels (1000 ppm F and 1500 ppm F). The prime objective of the study was to determine whether there was any difference in the anticaries efficacy between NaF and SMFP. The second objective was to assess the effect on caries protection of the incorporation of TMP into a NaF dentifrice formulation. The study was carried out to FDI protocol and involved 4,294 children aged 11-12 years at outset. These participants had been selected from a pool of 6,212 potential subjects on the basis of caries experience and dental eruption pattern. They were stratified by sex, examiner, presence of calculus and caries, and allocated at random to one of the six toothpastes under study. Clinical examinations were carried out at baseline and thereafter annually for 3 years. Bitewing radiographs of a subset of children were taken at baseline and at the end of the study. The outcome measure for the study, DMFS increment, was defined as the increase in caries over three years, taking into account changes occurring on individual tooth surfaces. After three years, clinical-only data for 3,517 children were available for the calculation of caries indices. The mean three-year DMFS increment for subjects using a dentifrice containing NaF alone was 6.4 per cent lower than for those using a dentifrice containing SMFP. The difference between the NaF+TMP users and the SMFP users was 8.1 percent.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "9817273", "18341378" ]

[ "Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study.", "Limited cytoprotective effects of amifostine in high-dose radioactive iodine 131-treated well-differentiated thyroid cancer patients: analysis of quantitative salivary scan." ]

[ "Salivary gland impairment is a well-recognized side effect following high-dose radioiodine treatment (HD-RIT). Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. Therefore, the effect of amifostine was studied in HD-RIT.\n Parenchymal function was assessed by quantitative salivary gland scintigraphy performed prospectively in 50 patients with differentiated thyroid cancer before and 3 months after HD-RIT with either 3 GBq iodine ((131)I) (n=21) or 6 GBq (131)I (n=29) in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously before HD-RIT and 25 patients served as controls, who received physiologic saline solution. Xerostomia was graded according to World Health Organization (WHO) criteria.\n Before HD-RIT in 25 control patients, uptake of technetium-99m (99mTc)-pertechnetate was 0.45%+/-0.16% and 0.42%+/-0.16% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function was significantly (P < .001) reduced by 40.2%+/-14.1% and 39.9%+/-15.3% in parotid and submandibular glands, respectively. Nine control patients developed grade I and two grade II xerostomia. In 25 amifostine-treated patients, uptake of 99mTc-pertechnetate was 0.46%+/-0.16% and 0.43%+/-0.17% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function of salivary glands was not significantly altered (P=.691) and xerostomia did not occur in any of these patients.\n Parenchymal damage in salivary glands caused by HD-RIT can significantly be reduced by amifostine, which may improve the quality of life of patients with differentiated thyroid cancer.", "The aim of present study was to investigate the cytoprotective effect of amifostine on salivary glands in 131I-treated differentiated thyroid cancer (DTC) patients using serial quantitative analysis of salivary gland scans.\n Serial quantitative salivary scintigraphies were performed in 80 newly diagnosed DTC patients (9 men, 71 women; mean age, 43.2 years old; range, 21-58 years old). Forty-two patients were assigned randomly to the amifostine treatment group, which received 300 mg/m2 amifostine intravenously before 131I administration.\n In both amifostine-treated and nontreated groups statistically significant declines of functional parameters after 131I treatment were revealed by quantitative salivary scintigraphy in DTC patients. Amifostine pretreatment did not prevent the parenchymal damage to major salivary gland function after 131I treatment (F = 1.37, p = 0.2461). However, the dose of 131I had significant effects on salivary gland function after 131I treatment (F = 9.72, p = 0.0002).\n The present study did not show cytoprotective effects of amifostine for DTC patients treated with 131I." ]

[ "17666597", "16394045", "9065105" ]

[ "Antepartum treatment without early cordocentesis for standard-risk alloimmune thrombocytopenia: a randomized controlled trial.", "Parallel randomized trials of risk-based therapy for fetal alloimmune thrombocytopenia.", "Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin." ]

[ "To evaluate the effectiveness and safety of two antenatal treatment regimens designed to optimally protect fetuses against intracranial hemorrhage resulting from alloimmune thrombocytopenia while minimizing the risks associated with fetal blood sampling. The study was limited to \"standard-risk\" patients, who were defined as women with documented alloimmune thrombocytopenia who had not delivered an infant with an intracranial hemorrhage in a prior pregnancy.\n In this prospective multicenter study of 73 women with documented alloimmune thrombocytopenia, patients were randomized to receive either intravenous immunoglobulin (IVIG) 2 g/kg/wk (group A) or IVIG 1 g/kg/wk plus prednisone 0.5 mg/kg/d (group B), starting at approximately 20 weeks of gestation. Fetal blood sampling was performed at approximately 32 weeks of gestation, and those with fetal platelet counts less than 30,000/mL(3) were given salvage therapy.\n There were two intracranial hemorrhages; neither was due to treatment failure. The average platelet counts at the time of fetal blood sampling were 121,600/mL(3) and 116,100/mL(3), and the average birth platelet counts were 169,400/mL(3) and 134,000/mL(3) for groups A and B, respectively. Twenty-seven percent of patients in group A and 17% in group B received salvage therapy, and only one neonate in each of these subsets had a birth platelet count less than 30,000/mL(3). There were four complications after 79 fetal blood sampling procedures, leading to cesarean deliveries between 32 and 37 weeks. There was a higher incidence of gestational diabetes and a tendency to more fluid retention, mood swings, insomnia, and jitteriness in patients on prednisone and of moderate-to-severe fatigue in those on high-dose IVIG alone.\n The outcomes of both treatment groups were excellent and comparable. Early cordocentesis is not necessary when treating alloimmune thrombocytopenia in patients who have not delivered an infant with an intracranial hemorrhage in a prior pregnancy.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00194987\n I.", "Antenatal therapy with intravenous immunoglobulin (IVIG) and prednisone has been shown to improve fetal thrombocytopenia and reduce the incidence of intracranial hemorrhage in neonatal alloimmune thrombocytopenia. Optimization of this therapy for individual patients, however, has yet to be achieved.\n In these parallel, randomized, multicenter studies, 78 patients in 79 pregnancies were stratified to 2 different treatment arms based on the presence of a peripartum intracranial hemorrhage in a previously affected sibling and/or the initial fetal platelet count. Patients with a history of an antenatal intracranial hemorrhage in a prior pregnancy were excluded.\n Forty women whose children from a previous birth had a peripartum intracranial hemorrhage or whose current fetus had an initial platelet count less than 20,000/mL3 were randomly assigned to receive IVIG plus prednisone or IVIG alone. The mean increase in fetal platelet counts in the following 3 to 8 weeks was 67,100/mL3 and 17,300/mL3, respectively (P < .001). Thirty-nine patients whose prior affected child did not have an intracranial hemorrhage and whose initial platelet count was more than 20,000/mL3 were randomly assigned to receive IVIG alone or prednisone alone. There were no significant differences, and 33 (85%) had birth platelet counts more than 50,000/mL3. There were 11 (6%) significant complications after a total of 175 fetal blood sampling procedures, 2 of which led to fetal or neonatal deaths.\n The spectrum of disease severity of alloimmune thrombocytopenia is reflected in the initial fetal platelet count and response to therapy. Fetal blood sampling may be associated with significant fetal/neonatal morbidity and mortality. Empiric therapy sufficient to treat the most severely affected fetuses will overtreat others and is likely to be associated with additional maternal morbidity.", "Our purposes were to investigate maternal infusions of intravenous gamma-globulin, to prevent intracranial hemorrhage, and to determine whether 1.5 mg dexamethasone and 60 mg prednisone per day add to the effect of intravenous gamma-globulin.\n Fifty-four women with alloimmune thrombocytopenia and thrombocytopenic fetuses were randomized to intravenous gamma-globulin 1 gm/kg per week with or without dexamethasone. Nonresponders after 4 to 6 weeks received continued intravenous gamma-globulin plus 60 mg of prednisone per day (\"salvage\").\n Dexamethasone did not add to the effect of intravenous gamma-globulin. Overall, there was a mean platelet increase from the first to the second fetal blood sampling of 36,000/microliters (n = 47) and from the first fetal blood sampling to birth of 69,000/microliters (n = 54). A total of 62% to 85% of fetuses responded. There were no intracranial hemorrhages. \"Salvage\" increased the platelet count in 5 of 10 nonresponders to intravenous gamma-globulin.\n Intravenous gamma-globulin treatment is appropriate for thrombocytopenic fetuses with alloimmune thrombocytopenia before use of weekly in utero platelet transfusions, even in severe thrombocytopenia." ]

[ "12214830", "9190979", "17466514" ]

[ "A prospective randomized study comparing retroperitoneal drainage with no drainage and no peritonization following radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer.", "A randomized study comparing retroperitoneal drainage with no drainage after lymphadenectomy in gynecologic malignancies.", "Randomised trial of drains versus no drains following radical hysterectomy and pelvic lymph node dissection: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group (EORTC-GCG) study in 234 patients." ]

[ "To evaluate the postoperative morbidity and lymphocyst formation in invasive cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (RHPL) with no drainage and no peritonization compared with retroperitoneal drainage and peritonization.\n Between July 1999 and May 2000, 100 patients with stage IA-IIA cervical cancer undergoing RHPL in Chiang Mai University Hospital were prospectively randomized to receive either no peritonization and no drainage (Group A = 48 cases) or retroperitoneal drainage and peritonization (Group B = 52 cases). Perioperative data and morbidity were recorded. Transabdominal and transvaginal sonography were performed at 4, 8 and 12 weeks postoperatively to detect lymphocyst formation.\n Both groups were similar regarding age, size and gross appearance of tumor, tumor histology and stage. There was no difference between groups in respect of operative time, need for blood transfusion, intraoperative complications, hospital stay, number of nodes removed, nodal metastases, and need for adjuvant radiation and chemotherapy. Asymptomatic lymphocysts were sonographically detected at 4, 8 and 12 weeks postoperatively in 3 (6.8%), 2 (4.6%), and 3 (7.7%) of 44, 43, and 39 patients, respectively in Group A, whereas none was found in Group B (P = 0.2). No significant difference was found in term of postoperative morbidity in the two groups.\n Routine retroperitoneal drainage and peritonization after RHPL for invasive cervical cancer can be safely omitted.", "To evaluate the clinical effectiveness of retroperitoneal drainage following lymphadenectomy in gynecologic surgery.\n One hundred thirty-seven consecutive patients undergoing systematic lymphadenectomy for gynecologic malignancies were randomized to receive (Group A, 68) or not (Group B, 69) retroperitoneal drainage. The pelvic peritoneum and the paracolic gutters were not sutured after node dissection. Perioperative data and complications were recorded.\n Clinical and surgical parameters were comparable in the two groups. Postoperative hospital stay was significantly shorter in Group B (P < 0.001), whereas the complication rate was significantly higher in Group A (P = 0.01). This was mainly due to a significant increase in lymphocyst and lymphocyst-related morbidity. Sonographic monitoring for lymphocyst showed free abdominal fluid in 18% of drained and 36% of not-drained patients (P = 0.03). Symptomatic ascites developed in 2 drained (3%) and 3 not-drained (4%) patients (NS), respectively.\n Prophylactic drainage of the retroperitoneum seems to increase lymphadenectomy-related morbidity and postoperative stay. Therefore, routine drainage following lymphadenectomy seems to be no longer indicated when the retroperitoneum is left open.", "Drainage, following radical hysterectomy and pelvic lymph node dissection to prevent postoperative lymphocyst formation and surgical morbidity, is controversial. To study the clinical significance of drainage, 253 patients were registered and 234 patients were randomised into two arms. In one arm (n=117) postoperative drainage was performed, in the other arm (n=117) no drains were inserted. In both arms closure of the peritoneum of the operating field was omitted. The main exclusion criteria were blood loss of more than 3000 ml during surgery or persistent oozing at the end of the operation. Clinical and ultrasound or CT-scan evaluation was done at one and 12 months postoperatively. The median follow-up amounted to 13.3 months. No difference in the incidence of postoperative lymphocyst formation or postoperative complications was found between the two study arms. The late (12 months) incidence of symptomatic lymphocysts was 3.4% (drains: 5.9%; no drains: 0.9%). The difference showed a p-value of 0.06 in Fisher's Exact test. The operating time was related to the occurrence of postoperative lymphocyst formation. It was concluded that drains can be safely omitted following radical hysterectomy and pelvic node dissection without pelvic reperitonisation in patients without excessive bleeding during or oozing at the end of surgery." ]

[ "18454611", "14505443" ]

[ "The effect of music therapy on anxiety in patients who are terminally ill.", "The effects of music therapy on the quality and length of life of people diagnosed with terminal cancer." ]

[ "The literature supporting the use of music therapy in palliative care is growing. However, the number of quantitative research studies investigating the use of music therapy in palliative care, and specifically anxiety, is limited.\n The aim of this research project was to examine the effectiveness of a single music therapy session in reducing anxiety for terminally ill patients.\n A randomized-controlled design was implemented and the following hypotheses tested. There will be a significant difference between the experimental and control groups on anxiety levels as demonstrated by the anxiety measurement of the Edmonton Symptom Assessment System (ESAS), and heart rate. The experimental group received a single music therapy intervention and the control group received a volunteer visit.\n Twenty-five participants with end-stage terminal disease receiving inpatient hospice services were recruited.\n The first hypothesis was supported. Results demonstrated a significant reduction in anxiety for the experimental group on the anxiety measurement of the ESAS (p = 0.005). A post hoc analysis found significant reductions in other measurements on the ESAS in the experimental group, specifically pain (p = 0.019), tiredness (p = 0.024) and drowsiness (p = 0.018). The second hypothesis was not supported.\n The study supports the use of music therapy to manage anxiety in terminally ill patients. Further studies are required to examine the effect of music therapy over a longer time period, as well as addressing other symptom issues.", "The purpose of this study was to evaluate the effects of music therapy on quality of life, length of life in care, physical status, and relationship of death occurrence to the final music therapy interventions of hospice patients diagnosed with terminal cancer. Subjects were adults who were living in their homes, receiving hospice care, and were diagnosed with terminal cancer. A total of 80 subjects participated in the study and were randomly assigned to one of two groups: experimental (routine hospice services and clinical music therapy) and control (routine hospice services only). Groups were matched on the basis of gender and age. Quality of life was measured by the Hospice Quality of Life Index-Revised (HQOLI-R), a self-report measure given every visit. Functional status of the subjects was assessed by the hospice nurse during every visit using the Palliative Performance Scale. All subjects received at least two visits and quality of life and physical status assessments. A repeated measures ANOVA revealed a significant difference between groups on self-report quality of life scores for visits one and two. Quality of life was higher for those subjects receiving music therapy, and their quality of life increased over time as they received more music therapy sessions. Subjects in the control group, however, experienced a lower quality of life than those in the experimental group, and without music, their quality of life decreased over time. There were no significant differences in results by age or gender of subjects in either condition. Furthermore, there were no significant differences between groups on physical functioning, length of life, or time of death in relation to the last scheduled visit by the music therapist or counselor. This study provides an overview of hospice/palliative care, explains the role of music therapy in providing care, and establishes clinical guidelines grounded in research for the use of music therapy in improving the quality of life among the terminally ill." ]

[ "3045281" ]

[ "Clinical trial of naloxone in birth asphyxia." ]

[ "To determine whether endogenous opiates play a role in the pathogenesis of perinatal asphyxia, a blinded clinical trial of naloxone, a competitive opiate receptor blocker, was undertaken in infants with low 1-minute Apgar scores. Of 85 infants with 1-minute Apgar score 0 to 3, 44 received an injection of naloxone (approximately 0.4 mg/kg) and 41 received saline solution. In 108 infants with 1-minute Apgar score 4 to 6, 54 received naloxone and 54 saline solution. In neither group was there a significant effect of naloxone on respiratory frequency or heart rate up to 30 minutes after injection, nor at 24 hours of age. In both groups active muscle tone of upper and lower limbs was increased by naloxone, a response that may not be beneficial in the face of inadequate oxygen delivery to vital organs. We conclude that naloxone at this dose had no readily apparent benefit in the resuscitation of the asphyxiated newborn infant." ]

[ "17822748", "11063636", "17290061" ]

[ "A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus.", "A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study.", "Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study." ]

[ "After initial surgery, there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma (CS). This study was designed to compare patient outcome following treatment with adjuvant whole abdominal irradiation (WAI) versus (vs.) chemotherapy for patients with this rare group of female pelvic malignancies.\n Eligible, consenting women with stage I-IV uterine CS, no more than 1 cm postsurgical residuum and/or no extra-abdominal spread had their treatments randomly assigned as either WAI or three cycles of cisplatin (C), ifosfamide (I), and mesna (M).\n 232 patients were enrolled, of whom 206 (WAI=105; CIM=101) were deemed eligible. Patient demographics and characteristics were similar between arms. FIGO stage (both arms) was: I=64 (31%); II=26 (13%); III=92 (45%); IV=24 (12%). The estimated crude probability of recurring within 5 years was 58% (WAI) and 52% (CIM). Adjusting for stage and age, the recurrence rate was 21% lower for CIM patients than for WAI patients (relative hazard [RH]=0.789, 95% confidence interval [CI]: (0.530-1.176), p=0.245, 2-tail test). The estimated death rate was 29% lower among the CIM group (RH=0.712, 95% CI: 0.484-1.048, p=0.085, two-tail test).\n We did not find a statistically significant advantage in recurrence rate or survival for adjuvant CIM over WAI in patients with uterine CS. However, the observed differences favor the use of combination chemotherapy in future trials.", "The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population.\n Patients were randomized to receive ifosfamide (1.5 g/m(2)/day) times 5 days every 3 weeks for eight courses with mesna uroprotection, with or without cisplatin (20 mg/m(2)/day) times 5 days. No patient had received previous chemotherapy.\n Of 224 patients entered on this study, 30 were ineligible for a variety of reasons, leaving 194 evaluable patients. Early in the study, the dose of the combination regimen was reduced by 20% (1 day) because of toxicity. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosfamide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), grade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 peripheral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. The proportion of patients responding to ifosfamide alone versus ifosfamide-cisplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvic, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for \"other\" metastatic sites of measurable disease. The relative odds ratio of response adjusted for measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lower confidence limit, 1.06). Progression-free survival (PFS) and survival data suggest that the combination offers a slight prolongation of PFS (relative risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confidence limit, 1.03; P = 0.071, one-tailed test).\n The addition of cisplatin to ifosfamide appears to offer a small improvement in progression-free survival over ifosfamide alone in the management of advanced carcinosarcoma of the uterus; the added toxicity may not justify the use of this combination.\n Copyright 2000 Academic Press.", "To determine if paclitaxel added to ifosfamide as first-line treatment for advanced uterine carcinosarcoma (CS) improves overall survival (OS), progression-free survival (PFS), response, and toxicity.\n Eligible patients had measurable stage III or IV, persistent, or recurrent uterine CS. Random assignment to treatment was between ifosfamide 2.0 g/m2 intravenously (IV) daily for 3 days (arm 1) or ifosfamide 1.6 g/m2 IV daily for 3 days plus paclitaxel 135 mg/m2 by 3-hour infusion day 1 (arm 2). Mesna was administered similarly (both arms); filgrastim began on day 4 (arm 2). Cycles were repeated every 21 days up to eight cycles.\n Of 214 patients enrolled, 179 were eligible (arm 1, 91 patients; arm 2, 88 patients). Arm 2 patients experienced more frequent and severe sensory neuropathy (grade 1 to 4; 8% v 30%). The crude response rate was 29% (arm 1) and 45% (arm 2). The odds of response stratified by performance status were 2.21 greater in arm 2 (P = .017). Median PFS and OS, respectively, for arm 1 compared with arm 2 were 3.6 v 5.8 months and 8.4 v 13.5 months, respectively. There was a 31% decrease in the hazard of death (hazard ratio [HR], 0.69; 95% CI, 0.49 to 0.97; P = .03) and a 29% decrease in the hazard of progression (HR, 0.71; 95% CI, 0.51 to 0.97; P = .03) relative to arm 1 when stratifying by performance status.\n OS was significantly improved in arm 2, and toxicities were as expected and manageable. However, the need for active new agents persists, given that OS remains relatively poor in this disease." ]

[ "7020612" ]

[ "Azathioprine in rheumatoid arthritis: double-blind study of full versus half doses versus placebo." ]

[ "To test whether azathioprine in effective in rheumatoid arthritis in doses smaller than those normally used the drug was tested at 2 dosage levels, 2.5 and 1.25 mg/kg/day (2.5 AZ and 1.25 AZ), against placebo under double-blind conditions over 24 weeks. Dropouts were 7 out of 15 in the 2.5 AZ group, 4 out of 14 in the 1.25 AZ group, and 2 out of 13 in the placebo group. Some significant improvement occurred in all 3 groups, including those on placebo. However, the 2.5 AZ group fared significantly better than the placebo group, while the 1.25 AZ group results tended to fall between the other 2 groups. We conclude that, in order to obtain the reported effectiveness of azathioprine in rheumatoid arthritis, it is necessary to start treatment with 2.5 mg/kg/day. Halving this dosage reduces the effectiveness of the drug." ]

[ "18823799", "19797987", "19574065" ]

[ "A multicenter, prospective, randomized, controlled trial of open reduction--internal fixation versus total elbow arthroplasty for displaced intra-articular distal humeral fractures in elderly patients.", "Incidence, management, and prognosis of early ulnar nerve dysfunction in type C fractures of distal humerus.", "A clinical comparison of two different double plating methods for intraarticular distal humerus fractures." ]

[ "We conducted a prospective, randomized, controlled trial to compare functional outcomes, complications, and reoperation rates in elderly patients with displaced intra-articular, distal humeral fractures treated with open reduction-internal fixation (ORIF) or primary semiconstrained total elbow arthroplasty (TEA). Forty-two patients were randomized by sealed envelope. Inclusion criteria were age greater than 65 years; displaced, comminuted, intra-articular fractures of the distal humerus (Orthopaedic Trauma Association type 13C); and closed or Gustilo grade I open fractures treated within 12 hours of injury. Both ORIF and TEA were performed following a standardized protocol. The Mayo Elbow Performance Score (MEPS) and Disabilities of the Arm, Shoulder and Hand (DASH) score were determined at 6 weeks, 3 months, 6 months, 12 months, and 2 years. Complication type, duration, management, and treatment requiring reoperation were recorded. An intention-to-treat analysis and an on-treatment analysis were conducted to address patients randomized to ORIF but converted to TEA intraoperatively. Twenty-one patients were randomized to each treatment group. Two died before follow-up and were excluded from the study. Five patients randomized to ORIF were converted to TEA intraoperatively because of extensive comminution and inability to obtain fixation stable enough to allow early range of motion. This resulted in 15 patients (3 men and 12 women) with a mean age of 77 years in the ORIF group and 25 patients (2 men and 23 women) with a mean age of 78 years in the TEA group. Baseline demographics for mechanism, classification, comorbidities, fracture type, activity level, and ipsilateral injuries were similar between the 2 groups. Operative time averaged 32 minutes less in the TEA group (P = .001). Patients who underwent TEA had significantly better MEPSs at 3 months (83 vs 65, P = .01), 6 months (86 vs 68, P = .003), 12 months (88 vs 72, P = .007), and 2 years (86 vs 73, P = .015) compared with the ORIF group. Patients who underwent TEA had significantly better DASH scores at 6 weeks (43 vs 77, P = .02) and 6 months (31 vs 50, P = .01) but not at 12 months (32 vs 47, P = .1) or 2 years (34 vs 38, P = .6). The mean flexion-extension arc was 107 degrees (range, 42 degrees -145 degrees) in the TEA group and 95 degrees (range, 30 degrees -140 degrees) in the ORIF group (P = .19). Reoperation rates for TEA (3/25 [12%]) and ORIF (4/15 [27%]) were not statistically different (P = .2). TEA for the treatment of comminuted intra-articular distal humeral fractures resulted in more predictable and improved 2-year functional outcomes compared with ORIF, based on the MEPS. DASH scores were better in the TEA group in the short term but were not statistically different at 2 years' follow-up. TEA may result in decreased reoperation rates, considering that 25% of fractures randomized to ORIF were not amenable to internal fixation. TEA is a preferred alternative for ORIF in elderly patients with complex distal humeral fractures that are not amenable to stable fixation. Elderly patients have an increased baseline DASH score and appear to accommodate to objective limitations in function with time.", "Displaced comminuted of the distal humerus in adults are among the most complex fractures to be managed effectively. The ulnar nerve is at high risk of impingement secondary to injury, operation, and postoperative rehabilitation in these fractures. In this study we focus on the incidence, management, and prognosis of early ulnar nerve dysfunction in the course of treating type C fractures of distal humerus.\n We examine a patient sample of 117 consecutive AO type C fractures of distal humerus, between June 1998 and October 2005. Twenty-nine patients exhibited preoperative ulnar nerve compression symptoms (incidence 24.8%) and were divided into two groups randomly, which received treatment of anterior subfascial transposition or in situ decompression of the ulnar nerve respectively, in conjunction with internal fixation with medial and lateral plates.\n The subgroup of 88 patients without preoperative ulnar nerve symptoms remained asymptomatic postoperatively (0% incidence of late ulnar nerve dysfunction). According to Bishop rating system, excellent and good results of ulnar nerve function were achieved in 13 of 15 patients (86.7%) in the transposition group, 8 of 14 patients (57.1%) in the in situ decompression group. The results difference is statistically significant (p < 0.05).\n We conclude that neurolysis and anterior subfascial transposition of vascularized ulnar nerve during open reduction and internal fixation of type C fractures of the distal humerus is beneficial in cases of early ulnat nerve dysfunction.", "This study compared clinical outcomes in patients with intraarticular distal humerus fractures treated using 2 different double plating methods.\n Seventeen patients were treated by perpendicular plating (group I) and 18 by parallel plating (group II) methods. Arc of flexion averaged 106 degrees +/-23 degrees in group I and 112 degrees +/-19 degrees in group II.\n Eleven patients in group I recovered full arc of flexion and 13 patients in group II achieved full arc of flexion. All patients obtained bone union, except 2 patients in group I. Nonunion in these patients developed in the supracondylar area. Complications developed in 6 patients in group I and in 8 in group II. No significant differences were found between the clinical outcomes of the 2o plating methods.\n Although more patients failed to achieve bony union in the perpendicular plating group, both parallel and orthogonal plates positioning can provide adequate stability and anatomic reconstruction of the distal humerus fractures.\n 2." ]

[ "8372870" ]

[ "Insulin-requiring diabetes in pregnancy: a randomized trial of active induction of labor and expectant management." ]

[ "Our purpose was to assess whether a program of expectant management of uncomplicated pregnancies in mothers with insulin-requiring gestational or pregestational class B reduces the incidence of cesarean birth.\n Two hundred women with uncomplicated, insulin-requiring diabetes at 38 weeks' gestation who were compliant with care and whose infants were judged appropriate for gestational age were randomly assigned to (1) active induction of labor within 5 days or (2) expectant management. The expectant management group was monitored with weekly physical examination and twice-weekly nonstress tests and amniotic fluid volume estimation until delivery.\n Expectant management increased the gestational age at delivery by 1 week. Approximately half (49%) of the mothers in the expectant management group required induction of labor for obstetric indications. The cesarean delivery rate was not significantly different in the expectant management group (31%) from the active induction group (25%). The mean birth weight (3672 +/- 407 gm) and percentage large for gestational age, as defined by birth weight > or = 90th percentile, of infants in the expectantly managed group (23%) was greater than those in the active induction group (3466 +/- 372 gm, p < 0.0001, 10% large for gestational age). This difference persisted after controlling for gestational age and maternal age and body weight (p < 0.01).\n In women with uncomplicated insulin-requiring gestational or class B pregestational diabetes, expectant management of pregnancy after 38 weeks' gestation did not reduce the incidence of cesarean delivery. Moreover, there was an increased prevalence of large-for-gestational-age infants (23% vs 10%) and shoulder dystocia (3% vs 0%). Because of these risks, delivery should be contemplated at 38 weeks and, if not pursued, careful monitoring of fetal growth must be performed." ]

[ "6803118", "16330203", "6811710", "6403808", "6777653" ]

[ "A prospective randomized clinical trial of total parenteral nutrition in children with cancer.", "Parenteral nutrition is not superior to replacement fluid therapy for the supportive treatment of chemotherapy induced oral mucositis in children.", "Comparison of morbidity in children requiring abdominal radiation and chemotherapy, with and without total parenteral nutrition.", "Effect of total parenteral nutrition on marrow recovery during induction therapy for acute nonlymphocytic leukemia in childhood.", "A clinical trial of hyperalimentation in children with metastatic malignancies." ]

[ "A prospective randomized clinical trial was undertaken to test the efficacy of total parenteral nutrition (TPN) among previously untreated children receiving abdominal/pelvic irradiation with or without adjuvant chemotherapy who were at risk for weight loss, malnutrition, and complications from treatment. Children were evaluated by weight/height determinations, anthropomorphic measurements, and laboratory studies. TPN was associated with an improved nutritional status during therapy as compared with control patients on ad libitum intake. However, when TPN was discontinued, weight declined and there were no differences among treated and control patients detected at three-month follow-up. Likewise there was no obvious effect from TPN on tolerance to therapy in the adequately nourished child. TPN as initial supportive therapy should be reserved for those children who are malnourished or marginally malnourished at the time of presentation. Close nutritional assessment during treatment is essential since approximately 25% of children undergoing abdominal/pelvic radiotherapy with chemotherapy can be expected to become malnourished during an initial course of therapy.", "Many paediatric oncology centres apply parenteral nutrition (PN) in children with severe oral mucositis after chemotherapy. However, no convincing data exist to support this treatment strategy. The aim of our study was to elucidate a possible advantage of PN versus intravenous replacement fluid therapy (FT). In a prospective randomized study, 30 children with mucositis WHO grade IV were assigned to receive either PN or intravenous replacement FT. Weight, total body water, fat-free mass (measured by impedance analysis) and peripheral white blood cells were assessed daily. For aspects of quality of life and economics, the length of hospital stay, the incidence of infections, the days on intravenous antibiotics and delay of scheduled chemotherapy were examined. Children with PN gained body weight significantly compared to baseline and to FT due to an augmentation of fat mass while total body water and fat-free mass significantly decreased. In children with FT, body weight remained stable while total body water and fat-free mass significantly increased, thereby loosing fat mass. We observed no differences in recovery of peripheral white blood cells (WBC), incidence of infections, hospitalization time, days on intravenous antibiotics, days on opioid analgesics and delay of the next scheduled chemotherapy cycle. Although children with PN gained weight in form of fat mass, this did not translate into a clinical benefit for the patients such as earlier recovery of WBC counts, shorter hospitalization time, a decreased use of analgesics or less delay of the next scheduled chemotherapy cycle. Our findings therefore do not support the hypothesis that PN is superior to FT when used for less than 10 days for oral mucositis.", "We evaluated the effectiveness of total parenteral nutrition and placing the \"bowel at rest,\" as compared to that of ad libitum food intake, on nutritional status and tolerance to combined chemotherapy and radiotherapy in a randomized, prospective trial in children with previously untreated malignancy requiring abdominal and pelvic irradiation and chemotherapy. Administration of TPN was found to be safe and efficacious in maintaining the children in good nutritional status during combined therapy; one-third of the control patients became malnourished and required TPN. There was no beneficial effect of \"bowel at rest\" and TPN on the ability of patients to tolerate combined therapies in terms of decreased toxicity; however, use of TPN was associated with improved adherence to chemotherapy schedules. Following termination of TPN or ad libitum food intake, and while receiving chemotherapy, the majority of the children who had previously received TPN lost significant weight. To date there has been no difference in mortality rate between the control and TPN groups. Although we conclude that TPN per se had little beneficial effect beyond that of maintaining good nutritional status, every child undergoing intensive combined therapy should have early and periodic assessments of nutritional status, so that the early signs of malnutrition can be detected, and the adverse effects of malnutrition can be prevented by nutritional replenishment, by TPN, or by other methods.", "Ten well-nourished children with acute nonlymphocytic leukemia (ANLL) were randomly assigned to groups that received (a) total parenteral nutrition (TPN) throughout the period of induction therapy or (b) standard nutritional support. Body mass and skin hypersensitivity reactions were better maintained in experimental patients. Patients on TPN had higher total white blood counts, absolute granulocyte counts, and platelet counts than did control patients during the course. No difference was apparent in the frequency of febrile episodes, or other aspects of the patients' courses. This preliminary report suggests that intensive nutritional support may accelerate the recovery of normal marrow function during induction therapy for ANLL.", "In a controlled, randomized prospective clinical trial the utility of intravenous hyperalimentation (IVH) in the administration of and tolerance to chemotherapy was tested. The conclusions reached were 1) IVH is safe with a tolerable infection rate; 2) infectious complications correlate significantly with the nutritional status of the patient, with the presence of IVH being only a secondary factor; 3) IVH may be used to rehabilitate patients nutritionally, even those on intensive chemotherapy; 4) the ability to deliver chemotherapy to patients seems to be improved by IVH, especially in malnourished patients in a late stage of disease." ]

[ "2139685", "1553138", "9195788", "8455920", "8248962", "8852193", "9832763", "7936257", "12006305", "2258521", "12161876", "11057994", "10918757" ]

[ "Measuring the impact of an acute stroke program on patient outcomes.", "Clinical nurse specialists as collaborative care managers.", "Evaluation of a critical pathway for stroke.", "The critical path method in stroke rehabilitation: lessons from an experiment in cost containment and outcome improvement.", "A model for management of patients with stroke during the acute phase. Outcome and economic implications.", "Case management: improving outcomes of care for ischemic stroke patients.", "Acute stroke patients comparing outcomes with and without case management.", "Effect of a stroke protocol on hospital costs of stroke patients.", "Does an integrated care pathway improve processes of care in stroke rehabilitation? A randomized controlled trial.", "The effect of systematic care planning after acute stroke in general hospital medical wards.", "Variance analysis applied to a stroke pathway: how this can improve efficiency of healthcare delivery.", "Cerebrovascular accident clinical pathway.", "The development of a stroke clinical pathway: an experience in a medium-sized community hospital." ]

[ "Stroke is the third leading cause of death in the United States, affecting 400,000 persons annually. A uniform medical treatment is yet to be established. Little nursing research has been conducted which measures the impact of specific nursing interventions on patient outcomes. The purpose of this study was to measure the impact of a nurse-managed acute stroke program on patient outcomes. Aspects of the stroke program included daily nursing assessment, patient teaching, two support groups, staff education, family discharge planning and telephone follow-up. Variables examined were length of stay, disposition, readmission and compliance factors. Charts of patients admitted during the first six months of 1987 (before implementation of the stroke program) were compared to those of patients admitted during the first six months of 1988 (after implementation of the stroke program). Findings support continued development of the stroke program. There are implications for nursing practice, education and research.", "nan", "The diagnosis of stroke, which is diagnosis-related group (DRG) 014, is the fourth most frequent discharge DRG at Macomb Hospital Center, Warren, Michigan. The length of stay for stroke was 7.52 days before intervention. Quality improvement techniques identified areas of delay that presented opportunities for improvement. After the initiation of a critical pathway that begins its interventions in the Emergency Department, the length of stay decreased to 6.33 days. Quality of care was also improved in delivery time of carotid artery ultrasound examinations, as well as in timeliness of obtaining head computed tomography scans and reports. This article describes the development, implementation, and results of a stroke critical pathway that was implemented to address excessive length of stay.", "This study tested the effects of a project network technique called the Critical Path Method (CPM) on the costs and outcomes of inpatient team stroke rehabilitation. On admission to a large, academic, inpatient rehabilitation hospital adults who had a recent (< 120 days) stroke were randomly assigned to receive rehabilitation services from a team trained in CPM (N = 53) or from usual care teams (N = 68). Results showed no significant difference between groups in length of stay, hospital charges, or functional status at discharge. CPM may be effective in patient care services that are less influenced by specialization, professional issues, and external regulation and in settings where patient outcomes are relatively fixed and predictable, and medical care is integrated across institutions.", "The purpose of the study was to develop a clinical pathway for patients with nonhemorrhagic stroke during the acute hospital phase to improve the quality of care and reduce costs.\n The pathway included standard admission orders and a swallow screen on day 1 of hospitalization. Physical therapy, occupational therapy, speech therapy, and social worker assessments were done on day 2. A physiatry consult was performed on day 3 if indicated, and by day 4 a discharge target date and disposition were addressed.\n Outcomes for 121 patients during the first year of pathway implementation are reported. The average length of stay on the acute service decreased from 10.9 days to 7.3 days (P < .05), reducing the charges per patient by 14.6%. Complications in the form of urinary tract infections and aspiration pneumonia rates decreased by 63.2% (P < .05) and 38.7%, respectively.\n We conclude that the implementation of a clinical pathway for patients with acute, nonhemorrhagic stroke resulted in a significant reduction in length of stay, charges, and complications while improving the quality of care.", "Stroke is a leading cause of death and disability in the United States. Health care reform and escalating health care costs have caused both consumers and health care providers to become more concerned regarding health care provision for stroke patients. A case management practice model used in a 540-bed teaching hospital resulted in improved outcomes for ischemic stroke patients in the areas of: (a) functional ability, (b) appointment compliance, (c) length of stay, and (d) cost.", "Stroke represents a major human and economic challenge to society. The literature suggests that interdisciplinary clinical pathways maximize stroke patient outcomes, whether care is delivered in a designated stroke unit or in a general medical service. In this article, the authors describe the case management model implemented at Columbus Regional Hospital, a 325-bed rural referral hospital in southeastern Indiana. A retrospective chart review compared 23 patients with non-hemorrhagic strokes using two different models of care delivery: unit-based nursing case management and standard nursing care. Differences in outcomes are reported in relation to interdisciplinary utilization, timeliness of referrals, patient education, discharge dispositions, home safety assessments, next-site-of-care communications, length of hospital stay, and patient satisfaction.", "To determine the impact of a protocol on hospitalization costs for patients admitted with stroke.\n Nonrandomized control trial in an urban community hospital with 376 beds.\n All patients admitted with a diagnosis-related group code of 014 (cerebrovascular disease) were included (N = 390). Patients with subdural hematoma (N = 2) or subarachnoid hemorrhage (N = 2) were excluded.\n A protocol for treatment of acute stroke was developed that included a critical path for nursing care, an algorithm for emergency department care, and suggested admission orders for physicians.\n The hospital information system computer database was searched for hospitalization charges, length of stay, tests performed, and treatments provided.\n Patients treated with the protocol had lower charges compared with historical (p = 0.026) and concurrent (p = 0.02) control groups. Lower charges were accounted for by a decreased length of stay in the protocol group compared with historical (p = 0.001) and concurrent (p = 0.13) controls. Tests and treatments provided were similar except that carotid Doppler studies and deep venous thrombosis prophylaxis were more frequently done in those treated with the protocol (p = 0.001 for carotid Doppler and p = 0.026 for deep venous thrombosis prophylaxis). There were no differences in outcome measures such as death or discharge disposition. Medical complications were similar in all groups.\n There were significant savings in hospitalization cost for patients with acute stroke after introduction of a treatment protocol. These savings were almost entirely related to decreased length of stay. The protocol led to modest differences in tests ordered and treatments provided.", "to evaluate whether integrated care pathways improve the processes of care in stroke rehabilitation.\n comparison of processes of care data collected in a randomized controlled trial.\n acute stroke patients undergoing rehabilitation randomized to receive integrated care pathways management (n=76) or conventional multidisciplinary care (n=76).\n proportion of patients meeting recommended standards for processes of care using a validated stroke audit tool.\n integrated care pathways methodology was associated with higher frequency of stroke specific assessments, notably testing for inattention (84% versus 60%; P=0.015) and nutritional assessment (74% versus 22%, P<0.001). Documentation of provision of certain information to patients/carers (89% versus 70%; P=0.024) and early discharge notification to general practitioners (80% versus 45%; P<0.001) were also more common in this group. There were no significant differences in the processes of interdisciplinary co-ordination and patient management between the integrated care pathways group and the control group.\n integrated care pathways may improve assessment and communication, even in specialist stroke settings.", "In a multidisciplinary study comprising 280 patients with acute cerebrovascular disease, the functional capacity was followed from the acute stage onwards with a test battery mainly measuring activities of daily living and motor capacity. Systematized care procedures with written care plans in accordance with the nursing process model, together with a booklet of guidelines in stroke care, were introduced during an experimental period in the care of 173 of the stroke victims. The remaining 107 patients received conventional care. The functional improvements were equal from a statistical standpoint in these two groups. However, in the group, which received special activities, there was a significant decrease in bed days, and a slightly larger number were able to return to their own homes. Compared with another stroke population from the same hospital, measured with the same functional instrument 7 years ago, the patients in this study seemed better off from a functional standpoint. For the individual severely-disabled patient, the care planning procedures seemed to be valuable and an effective way of promoting communication between different units. The difficulties in introducing new routines for documentation are discussed.", "Stroke is a complicated disease that requires a multidisciplinary approach for its management. We postulated that variance analysis applied to a stroke pathway, by identifying major problem areas and encouraging timely corrective actions, would lead to more efficient healthcare delivery to hospitalised stroke patients.\n Prospectively collected variance data from consecutive stroke patients discharged from a tertiary hospital in Singapore during a 3-month period in 2000 were used to identify the major variances causing increased length of stay. These were compared and contrasted to variance data collected during the same 3-month period in the subsequent year (2001), after the implementation of stroke pathway and the availability of monthly variance analysis reports. Patient characteristics and outcome measures were also compared between the two study periods.\n The four major variances that accounted for increased length of stay were, in descending order of the number of patients affected, awaiting bed availability in step-down facilities, delay in head computed tomographic scan performance, awaiting family's decision on discharge plan and incomplete application submitted to step-down facilities. After implementation of the stroke pathway with ongoing variance analysis, all four variances showed different extent of improvements. There were no significant differences in patient characteristics between the two study periods, whereas the average length of stay significantly diminished in the late study period with a trend for decreased in-hospital mortality, compared to the early study period.\n Variance analysis applied in the context of a stroke pathway was effective in identifying major variances causing increased length of stay. This allowed targeted intervention to improve efficiency of healthcare delivery to stroke patients.", "The cerebrovascular accident (CVA) clinical pathway project was selected to complement the work already underway within the West Moreton Health Services District such as the development of a continuum of care model, revision of work practices to complement the new hospital redevelopment and encouraging team and evidence-based approaches to problem solving. Specific objectives were set for the project along with a detailed evaluation plan. A steering group was convened to run the project and a full time project officer was appointed. At the end of the 12 month period all the objectives were met. Specific achievements included a reduction in the overall average length of stay for those patients who experience CVA, improved clinical outcomes and a more effective use of resources. Quality of care has been improved through the preparation of specialized clinical pathway documentation, education packages, patient surveys, focus groups, independent reviews and benchmarking. Complementing these measures has been a series of process changes and environmental modifications. Furthermore, good working relationships have been established with private sector providers of health care and other external bodies. The development of the CVA clinical pathway at the Ipswich Hospital has meant timely referrals and a streamlined assessment and referral process to get patients into rehabilitation sooner. It has promoted good communication between, and recognition of, the professional roles of various team members and has put the patient back at the centre of the care process.", "Patients with acute ischemic strokes were studied in a medium-sized community hospital in Mississippi. Studies were done before and after implementation of the stroke clinical care pathway with emphasis on the following clinical indicators: 1) performance of a brain CT scan, 2) the search for the etiology of the stroke, 3) whether the patient was treated emergently for hypertension, 4) the use of measures to prevent deep-vein thrombosis, and 5) prophylactic drug treatment against recurrent stroke after hospital discharge. Following application of the clinical pathway, there was a significant improvement in all the clinical indicators that were felt to require further attention and none had a setback. The length of hospital stay was decreased, and there was no significant increase in the hospital costs in the post-pathway study despite an increase in the number of diagnostic and therapeutic procedures performed. When applied properly, clinical pathways can effectively mobilize hospital resources, maximize quality of care, and at the same time minimize costs." ]

[ "11999177", "15831542", "9743780", "16893677", "1958910", "11903763", "12757433", "16929034", "12950483" ]

[ "Real-time, evidence-based medicine instruction: a randomized controlled trial in a neonatal intensive care unit.", "Failure of Internet-based audit and feedback to improve quality of care delivered by primary care residents.", "The impact of an individual tutorial session on MEDLINE use among obstetrics and gynaecology residents in an academic training programme: a randomized trial.", "What factors are associated with the integration of evidence retrieval technology into routine general practice settings?", "Online access to MEDLINE in clinical settings: impact of user fees.", "Resident utilization of information technology.", "Educational workshop improved information-seeking skills, knowledge, attitudes and the search outcome of hospital clinicians: a randomised controlled trial.", "McMaster PLUS: a cluster randomized clinical trial of an intervention to accelerate clinical use of evidence-based information from digital libraries.", "Effect of a triage-based E-mail system on clinic resource use and patient and physician satisfaction in primary care: a randomized controlled trial." ]

[ "The study assesses potential for improving residents' evidence-based medicine searching skills in MEDLINE through real-time librarian instruction.\n Ten residents on a rotation in a neonatal intensive care unit participated.\n Residents were randomized into an instruction and a non-instruction group. Residents generated questions from rounds and searched MEDLINE for answers. Data were collected through observation, search strategy analysis, and surveys. Librarians observed searches and collected data on questions, searching skills, search problems, and the test group's instruction topics. Participants performed standardized searches before, after, and six-months after intervention and were scored using a search strategy analysis tool (1 representing highest score and 5 representing lowest score). Residents completed pre- and post-intervention surveys to measure opinions about MEDLINE and search satisfaction.\n Post-intervention, the test group formulated better questions, used limits more effectively, and reported greater confidence in using MEDLINE. The control group expressed less satisfaction with retrieval and demonstrated more errors when limiting. The test and control groups had the following average search scores respectively: 3.0 and 3.5 (pre-intervention), 3.3 and 3.4 (post-intervention), and 2.0 and 3.8 (six-month post-intervention).\n Data suggest that measurable learning outcomes were achieved. Residents receiving instruction improved and retained searching skills six-months after intervention.", "To determine the effectiveness of Internet-based audit and feedback to physicians to improve care for diabetes and hypertension.\n Time-series analysis of an intervention.\n The study setting was Harvard Vanguard Medical Associates, a 14-site multispecialty group in greater Boston. The study period was July 1997-June 1999.\n were 12 primary care internal medicine residents who provided care to adult patients with diabetes (n = 76 pre-intervention and n = 88 post-intervention), hypertension (n = 329 pre-intervention and n = 338 post-intervention), or both (n = 62 pre-intervention and n = 71 post-intervention). We determined the proportion of each resident's patients whose care fulfilled national guidelines for quality (i.e. diabetes patients had hemoglobin testing in the previous 6 months or hypertension patients received a beta-blocker or diuretic in the same time period). After meeting individually with each resident to obtain informed consent and to encourage participation, we sent each resident information for accessing his or her practice profile on a secure website. The main outcome measures were (i) the proportion of resident physicians who accessed their profiles and (ii) change following the intervention in the proportion of patients whose care followed national guidelines.\n Over a 1-year period, only four of the 12 residents accessed their websites. One of the residents visited her site three times, while the other three residents visited their sites once each. In interrupted time-series analyses, the intervention had no discernible effect on adherence to practice guidelines for diabetes or hypertension.\n The lack of participation in this Internet-based intervention may have important implications for the development of future programs that require physicians to interact with technology to improve quality of care.", "Over the past decade, on-line databases have become increasingly popular among health care professionals. As a group, these 'end-users' report utilizing databases to keep abreast of medical progress, to conduct research and to address specific patient care issues. Throughout the literature, medical professionals ('content experts') have proved to be less effective searchers than librarians ('search experts'). The potential implications of this discrepancy are worrysome. For any given clinical scenario, for example, published reports may reach contradictory conclusions. A poorly skilled searcher may not retrieve enough articles to appreciate this fact. Optimizing searching skills is therefore a worthwhile goal. As a first step, many medical schools introduce students to on-line databases, most notably MEDLINE. Residency is an ideal time to continue this training. A recognized obstacle to provide residents with formal MEDLINE instruction is time constraint. We therefore conducted this study to ascertain the impact an individual 1-hour tutorial session would have on MEDLINE utilization among obstetrics and gynecology residents training at an academic medical centre. Outcome measures included MEDLINE search frequency, duration, recall, precision and searcher satisfaction. Search recall measures the searcher's ability to retrieve articles deemed relevant to the question at hand. Search precision gauges the searchers' ability to eliminate irrelevant articles. Although the sessions were well received, we were unable to demonstrate an improvement in the outcome measures analysed. Further research is therefore indicated so that cost-effective educational strategies can be recommended for wide-scale use.", "Information retrieval systems have the potential to improve patient care but little is known about the variables which influence clinicians' uptake and use of systems in routine work.\n To determine which factors influenced use of an online evidence retrieval system.\n Computer logs and pre- and post-system survey analysis of a 4-week clinical trial of the Quick Clinical online evidence system involving 227 general practitioners across Australia.\n Online evidence use was not linked to general practice training or clinical experience but female clinicians conducted more searches than their male counterparts (mean use=14.38 searches, S.D.=11.68 versus mean use=8.50 searches, S.D.=9.99; t=2.67, d.f.=157, P=0.008). Practice characteristics such as hours worked, type and geographic location of clinic were not associated with search activity. Information seeking was also not related to participants' perceived information needs, computer skills, training nor Internet connection speed. Clinicians who reported direct improvements in patient care as a result of system use had significantly higher rates of system use than other users (mean use=12.55 searches, S.D.=13.18 versus mean use=8.15 searches, S.D.=9.18; t=2.322, d.f.=154 P=0.022). Comparison of participants' views pre- and post- the trial, showed that post-trial clinicians expressed more positive views about searching for information during a consultation (chi(2)=27.40, d.f.=4, P< or =0.001) and a significantly greater number reported seeking information between consultations as a result of having access to an online evidence system in their consulting rooms (chi(2)=9.818, d.f.=2, P=0.010).\n Clinicians' use of an online evidence system was directly related to their reported experiences of improvements in patient care. Post-trial clinicians positively changed their views about having time to search for information and pursued more questions during clinic hours.", "The effect of introducing user fees on the frequency and quality of MEDLINE searching with GRATEFUL MED by physicians in clinical settings was tested. After training and free use (prior study), consenting participants were randomly allocated to pay searching costs (pay group) or continue without fees (no pay group). Fifty-nine physicians participated. Among the prior study's frequent searchers, the pay group searched at less than one third of the rate of those assigned to no pay. For less frequent searchers in the prior study, only 48% of those assigned to pay did any searches, compared with 85% for the no pay group (P = 0.006), and for those who did search, their frequency was almost half. However, there was no significant difference in the quality of searches; both groups demonstrated about equivalent recall (P = 0.77), but significantly lower precision (P = 0.03) than for the librarian's independent searches. Similarly, there was no difference in the proportion of searches affecting clinical decisions for the two groups. Thus, imposing user charges for online searching in clinical settings after a period of free use adversely affects searching quantity, but not quality. MEDLINE providers should consider whether user fees will undermine its benefits.", "To determine if a simple educational intervention can increase resident physician literature search activity.\n Randomized controlled trial.\n University hospital-based internal medicine training program.\n Forty-eight medical residents rotating on the general internal medicine service.\n One-hour didactic session, the use of well-built clinical question cards, and practical sessions in clinical question building.\n Objective data from the library information system that included the number of log-ons to medline, searching volume, abstracts viewed, full-text articles viewed, and time spent searching. Median search activity as measured per person per week (control vs intervention): number of log-ons to medline (2.1 vs 4.4, P <.001); total number of search sets (24.0 vs 74.2, P <.001); abstracts viewed (5.8 vs 17.7, P=.001); articles viewed (1.0 vs 2.6, P=.005); and hours spent searching (0.8 vs 2.4, P <.001).\n A simple educational intervention can markedly increase resident searching activity.", "A double-blind randomised controlled trial was conducted on a group of Hong Kong hospital clinicians. The objective was to test if a three-hour educational workshop (with supervised hands-on practice) is more effective (than no training) to improve clinical question formulation, information-seeking skills, knowledge, attitudes, and search outcomes. The design was a post-test-only control group; recruitment by stratified randomization (by profession), blocked at 800. End-user training was more effective than no training in improving clinical question formulation, in raising awareness, knowledge, confidence and use of databases, but had made no impact on preference for secondary databases. It changed the attitude of clinicians to become more positive towards the use of electronic information services (EIS). Participants had higher search performance and outcomes (satisfaction with information obtained (NNT = 3), EIS satisfaction (NNT = 3) and success in problem solving (NNT = 4)). The workshop improved knowledge and skills in evidence-based searching, but this effect gradually eroded with time. Search logs confirmed that follow-up is required if effects are to be sustained. Longer effects on search behaviours appear to be positive. A randomised controlled trial is valuable in identifying cause-and-effect relations and to quantify the magnitude of the effects for management decision-making.", "Physicians have difficulty keeping up with new evidence from medical research.\n We developed the McMaster Premium LiteratUre Service (PLUS), an internet-based addition to an existing digital library, which delivered quality- and relevance-rated medical literature to physicians, matched to their clinical disciplines. We evaluated PLUS in a cluster-randomized trial of 203 participating physicians in Northern Ontario, comparing a Full-Serve version (that included alerts to new articles and a cumulative database of alerts) with a Self-Serve version (that included a passive guide to evidence-based literature). Utilization of the service was the primary trial end-point.\n Mean logins to the library rose by 0.77 logins/month/user (95% CI 0.43, 1.11) in the Full-Serve group compared with the Self-Serve group. The proportion of Full-Serve participants who utilized the service during each month of the study period showed a sustained increase during the intervention period, with a relative increase of 57% (95% CI 12, 123) compared with the Self-Serve group. There were no differences in these proportions during the baseline period, and following the crossover of the Self-Serve group to Full-Serve, the Self-Serve group's usage became indistinguishable from that of the Full-Serve group (relative difference 4.4 (95% CI -23.7, 43.0). Also during the intervention and crossover periods, measures of self-reported usefulness did not show a difference between the 2 groups.\n A quality- and relevance-rated online literature service increased the utilization of evidence-based information from a digital library by practicing physicians.", "E-mail communication between patients and their providers has diffused slowly in clinical practice. To address concerns about the use of this technology, we performed a randomized controlled trial of a triage-based e-mail system in primary care. DESIGN AND PATIENTS/PARTICIPANTS: Physicians in 2 university-affiliated primary care centers were randomized to a triage-based e-mail system promoted to their patients. E-mails from patients of intervention physicians were routed to a central account and parsed to the appropriate staff for response. Control group physicians and their patients did not have access to the system. We collected information on patient e-mail use, phone calls, and visit distribution by physician over the 10 months and performed physician and patient surveys to examine attitudes about communication.\n E-mail volume was greater for intervention versus control physicians (46 weekly e-mails per 100 scheduled visits vs 9 in the control group at the study midpoint; P <.01) but there were no between-group differences in phone volume (67 weekly phone calls per 100 scheduled visits vs 55 in the control group; P =.45) or rates of patient no-shows (5% in both groups; P =.77). Intervention physicians reported more favorable attitudes toward electronic communication than did control physicians but there were no differences in attitudes toward patient or staff communication in general. There were few between-group differences in patient attitudes toward electronic communication or communication in general.\n E-mail generated through a triage-based system did not appear to substitute for phone communication or to reduce visit no-shows in a primary care setting. Physicians' attitudes toward electronic communication were improved, but physicians' and patients' attitudes toward general communication did not change. Growth of e-mail communication in primary care settings may not improve the efficiency of clinical care." ]

[ "11157015", "3399417", "9243585", "15484202", "2587289", "15774341" ]

[ "Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial.", "The effect of aerobic exercise on patient reports of nausea.", "Effects of exercise on fatigue, physical functioning, and emotional distress during radiation therapy for breast cancer.", "Exercise manages fatigue during breast cancer treatment: a randomized controlled trial.", "Effects of aerobic interval training on cancer patients' functional capacity.", "A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment." ]

[ "Self-directed and supervised exercise were compared with usual care in a clinical trial designed to evaluate the effect of structured exercise on physical functioning and other dimensions of health-related quality of life in women with stages I and II breast cancer.\n One hundred twenty-three women with stages I and II breast cancer completed baseline evaluations of generic and disease- and site-specific health-related quality of life, aerobic capacity, and body weight. Participants were randomly allocated to one of three intervention groups: usual care (control group), self-directed exercise, or supervised exercise. Quality of life, aerobic capacity, and body weight measures were repeated at 26 weeks. The primary outcome was the change in the Short Form-36 physical functioning scale between baseline and 26 weeks.\n Physical functioning in the control group decreased by 4.1 points, whereas it increased by 5.7 points and 2.2 points in the self-directed and supervised exercise groups, respectively (P =.04). Post hoc analysis showed a moderately large (and clinically important) difference between the self-directed and control groups (9.8 points; P =.01) and a more modest difference between the supervised and control groups (6.3 points; P =.09). No significant differences between groups were observed for changes in quality of life scores. In a secondary analysis of participants stratified by type of adjuvant therapy, supervised exercise improved aerobic capacity (+3.5 mL/kg/min; P =.01) and reduced body weight (-4.8 kg; P <.05) compared with usual care only in participants not receiving chemotherapy.\n Physical exercise can blunt some of the negative side effects of breast cancer treatment, including reduced physical functioning. Self-directed exercise is an effective way to improve physical functioning compared with usual care. In participants not receiving chemotherapy, supervised exercise may increase aerobic capacity and reduce body weight compared with usual care.", "nan", "PURPOSES/OBJECTIVES: To test the hypothesis that women participating in a walking exercise program during radiation therapy treatment for breast cancer would demonstrate more adaptive responses as evidenced by higher levels of physical functioning and lower levels of symptom intensity than women who did not participate.\n Experimental, two-group pretest, post-test.\n Two university teaching hospital outpatient radiation therapy departments.\n 46 women beginning a six-week program of radiation therapy for early stage breast cancer.\n Following random assignment, subjects in the exercise group maintained an individualized, self-paced, home-based walking exercise program throughout treatment. The control group received usual care. Dependent variables were measured prior to and at the end of radiation therapy. In addition, symptoms were assessed at the end of three weeks of treatment.\n Participation in the walking exercise program, physical functioning fatigue, emotional distress, and difficulty sleeping.\n Hypothesis testing by multivariate analysis of covariance, with pretest scores as covariates, indicated significant differences between groups on outcome measures (p < 0.001). The exercise group scored significantly higher than the usual care group on physical functioning (p = 0.003) and symptom intensity, particularly fatigue, anxiety, and difficulty sleeping. Fatigue was the most frequent and intense subjective symptom reported.\n A self-paced, home-based walking exercise program can help manage symptoms and improve physical functioning during radiation therapy.\n Nurse-prescribed and -monitored exercise is an effective, convenient, and low-cost self-care activity that reduces symptoms and facilitates adaptation to breast cancer diagnosis and treatment.", "Fatigue is the most prevalent and debilitating symptom experienced by breast cancer patients receiving adjuvant chemotherapy or radiation therapy and few evidence-based treatments are available to manage this distressing side-effect. The purpose of this multi-institutional randomized controlled trial was to determine the effects of exercise on fatigue levels during treatment for breast cancer. Sedentary women (N=119) with Stage 0-III breast cancer receiving outpatient adjuvant chemotherapy or radiation therapy were randomized to a home-based moderate-intensity walking exercise program or to usual care for the duration of their cancer treatment. Of participants randomized to exercise, 72% adhered to the exercise prescription; 61% of the usual care group adhered. The intention-to-treat analysis revealed no group differences in part because of a dilution of treatment effect as 39% of the usual care group exercised and 28% of the exercise group did not. When exercise participation was considered using the data analysis method of instrumental variables with principal stratification, a clinically important and statistically significant (p=0.03) effect of exercise on pretest-to-posttest change in fatigue levels was demonstrated. Adherence to a home-based moderate-intensity walking exercise program may effectively mitigate the high levels of fatigue prevalent during cancer treatment.", "The effect of a 10-week aerobic interval-training cycle ergometer protocol on the functional capacity (VO2Lmax) of 45 women receiving chemotherapy for treatment of Stage II breast cancer was studied. Subjects were stratified by baseline functional capacity (+/- 1 MET) and randomized to experimental (EX), placebo (PL), and control (CO) groups. EX subjects completed a 10-week, 3 times/week exercise training program; PL subjects participated in 10 weeks of nonaerobic stretching and flexibility exercises; the CO group maintained normal activities. The EX group showed significant, p less than .05, improvement on pre- to posttest VO2Lmax as well as workload and test time compared to the PL and CO groups. The interval-training exercise intervention was effective in improving the functional capacity of Stage II breast cancer patients on adjuvant chemotherapy.", "This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy. The study was designed as a randomised controlled trial (RCT). Physical functioning, fatigue and Quality of Life (QoL) outcomes were evaluated pre and post a 12-week intervention. The results showed that after 12 weeks the women who participated in the exercise programme (n = 12) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls (n = 10). Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance. These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe, well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer. Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women. Future studies need to address these issues and determine if these short-term benefits can be sustained." ]

[ "9210279", "17364418", "10883563" ]

[ "Feminist-cognitive-behavioral and process-psychodynamic treatments for men who batter: interaction of abuser traits and treatment models.", "A cognitive behavioral therapy for alcohol-dependent domestic violence offenders: an integrated substance abuse-domestic violence treatment approach (SADV).", "The San Diego Navy experiment: an assessment of interventions for men who assault their wives." ]

[ "At a community-based domestic violence program, 218 men with a history of partner abuse were randomly assigned to either feminist-cognitive-behavioral or process-psychodynamic group treatments. The treatments were not hypothesized to differ in outcome. However, men with particular characteristics were expected to have lower recidivism rates depending on the type of treatment received. Treatment integrity was verified through audio-taped codings of each session. The partners of 79% of the 136 treatment completers gave reports of the men's behavior an average of 2 years post-treatment. These reports were supplemented with arrest records and self-reports. Rates of violence did not differ significantly between the two types of treatment nor did reports from the women of their fear level, general changes perceived in the men, and conflict resolution methods. However, interaction effects were found between some offender traits and the two treatments. As predicted, men with dependent personalities had better outcomes in the process-psychodynamic groups and those with antisocial traits had better outcomes in the cognitive-behavioral groups. The results suggest that more effective treatment may occur if it is tailored to specific characteristics of offenders.", "This pilot study evaluated the efficacy of a twelve-session cognitive behavioral group therapy for alcohol-dependent males with co-occurring interpersonal violence (IPV). Participants were 85 alcohol-dependent males who were arrested for domestic violence within the past year. Seventy-eight male adults were randomized to either a cognitive behavioral Substance Abuse Domestic Violence (SADV) group (N = 40) or a Twelve-Step Facilitation (TSF) Group (N = 38). There was no significant difference between SADV versus TSF in the number of sessions attended. Regarding substance use, the group assigned to SADV reported using alcohol significantly fewer days (eg, 90 days of abstinence across the 12 weeks of treatment) as compared to the TSF group. Regarding physical violence, there was a trend for participants in the SADV condition to achieve a greater reduction in the frequency of violent episodes across time compared to individuals in the TSF group. These data suggest the promise of the SADV group therapy approach for alcohol-dependent males with a history of IPV who present for substance abuse treatment.", "Three different 12-month interventions for servicemen who had been substantiated as having physically assaulted their wives were used and the outcomes examined. The 861 couples of the study were randomly assigned to 4 groups: a men's group, a conjoint group, a rigorously monitored group, and a control group. Cognitive-behavioral interventions were implemented for the men's and conjoint groups, and outcome data were gathered from male perpetrators and female victims at roughly 6-month intervals over the approximately 18-month experimental period. Data analyses revealed nonsignificant differences between the experimental groups over a variety of outcome measures." ]

[ "15919846", "18055007", "16950654", "12610030", "11211636" ]

[ "Transtheoretical model-chronic disease care for obesity in primary care: a randomized trial.", "Transtheoretical model-based multiple behavior intervention for weight management: effectiveness on a population basis.", "Comparison of two email-delivered, pedometer-based interventions to promote walking among insufficiently active women.", "Changes in diabetes self-care behaviors make a difference in glycemic control: the Diabetes Stages of Change (DiSC) study.", "The impact of behavioral counseling on stage of change in fat intake, physical activity, and cigarette smoking in adults at increased risk of coronary heart disease." ]

[ "To compare health benefits achieved in a transtheoretical model-chronic disease (TM-CD) minimal intervention for obesity vs. augmented usual care (AUC). Research Method and Procedures: This was a 2-year, randomized clinical trial with overweight or obese men and women from 15 primary care sites. AUC (n = 336) included dietary and exercise advice, prescriptions, and three 24-hour dietary recalls every 6 months. TM-CD care (n = 329) included AUC elements plus \"stage of change\" (SOC) assessments for five target behaviors every other month, mailed SOC and target behavior-matched workbooks, and monthly telephone calls from a weight-loss advisor. Weight change was the primary outcome.\n Repeated measures models under the missing at random assumption yielded nonsignificant adjusted differences between the AUC and TM-CD groups for weight change, waist circumference, energy intake or expenditure, blood pressure, and blood lipids. The pattern of change over time suggested that TM-CD participants were trying harder to impact target behaviors during the first 6 to 12 months of the trial but relapsed afterward. Sixty percent of trial participants maintained their baseline weights for 18 to 24 months.\n A combination of mailed patient materials and monthly telephone calls based on the transtheoretical model and some elements of chronic disease care is not powerful enough, relative to AUC, to alter target behaviors among overweight primary care patients in an obesogenic environment. AUC may be sufficient to maintain weights among at-risk primary care patients.", "The increasing prevalence of overweight and obesity underscores the need for evidence-based, easily disseminable interventions for weight management that can be delivered on a population basis. The Transtheoretical Model (TTM) offers a promising theoretical framework for multiple behavior weight management interventions.\n Overweight or obese adults (BMI 25-39.9; n=1277) were randomized to no-treatment control or home-based, stage-matched multiple behavior interventions for up to three behaviors related to weight management at 0, 3, 6, and 9 months. All participants were re-assessed at 6, 12, and 24 months.\n Significant treatment effects were found for healthy eating (47.5% versus 34.3%), exercise (44.90% versus 38.10%), managing emotional distress (49.7% versus 30.30%), and untreated fruit and vegetable intake (48.5% versus 39.0%) progressing to Action/Maintenance at 24 months. The groups differed on weight lost at 24 months. Co-variation of behavior change occurred and was much more pronounced in the treatment group, where individuals progressing to Action/Maintenance for a single behavior were 2.5-5 times more likely to make progress on another behavior. The impact of the multiple behavior intervention was more than three times that of single behavior interventions.\n This study demonstrates the ability of TTM-based tailored feedback to improve healthy eating, exercise, managing emotional distress, and weight on a population basis. The treatment produced a high level of population impact that future multiple behavior interventions can seek to surpass.", "Research on the effect of email-delivered, pedometer-based interventions on walking behavior and transtheoretical model (TTM) constructs is lacking. Therefore, the purpose of this study was to compare the effectiveness of two email-delivered, pedometer-based interventions designed to increase walking and TTM construct scores among insufficiently active women. Participants were randomly assigned to one of two 6-week intervention groups. Both groups wore pedometers, submitted step logs, and received weekly email reminders. One group also received in the emails suggested strategies based on TTM for increasing physical activity. Of the 74 women who began the study, 56 (age=41.5+/-7.6 years; body mass index=31.2+/-6.6kg/m(2); 86% Caucasian) completed the International Physical Activity Questionnaire and TTM questionnaires at baseline and post-intervention. Participants in both groups combined increased weekly time spent walking (p=0.002) and their scores on TTM cognitive processes, behavioral processes, pros, and cons changed (p< or =0.001) from baseline to post-intervention. The changes in walking and TTM scores did not differ between groups (p>0.05). The results of this study indicate that email-delivered, pedometer-based interventions may impact walking and most TTM scores among insufficiently active women. Although preliminary, the findings provide additional evidence that this low-cost method of intervening may be an effective approach to combat physical inactivity in women.", "This study compared diabetes Treatment As Usual (TAU) with Pathways To Change (PTC), an intervention developed from the Transtheoretical Model of Change (TTM), to determine whether the PTC intervention would result in greater readiness to change, greater increases in self-care, and improved diabetes control.\n Participants were stratified by diabetes treatment and randomized to treatment with PTC or TAU as well as being randomized regarding receipt of free blood testing strips. The PTC consisted of stage-matched personalized assessment reports, self-help manuals, newsletters, and individual phone counseling designed to improve readiness for self-monitoring of blood glucose (SMBG), healthy eating, and/or smoking cessation. A total of 1029 individuals with type 1 and type 2 diabetes who were in one of three pre-action stages for either SMBG, healthy eating, or smoking were recruited.\n For the SMBG intervention, 43.4% of those receiving PTC plus strips moved to an action stage, as well as 30.5% of those receiving PTC alone, 27.0% of those receiving TAU plus strips, and 18.4% of those receiving TAU alone (P < 0.001). For the healthy eating intervention, more participants who received PTC than TAU (32.5 vs. 25.8%) moved to action or maintenance (P < 0.001). For the smoking intervention, more participants receiving PTC (24.3%) than TAU (13.4%) moved to an action stage (P < 0.03). In intention-to-treat (ITT) analysis of those receiving the SMBG intervention, PTC resulted in a greater reduction of HbA(1c) than TAU, but this did not reach statistical significance. However, in those who moved to an action stage for the SMBG and healthy eating interventions, HbA(1c) was significantly reduced (P < 0 0.001). Individuals who received the healthy eating intervention decreased their percentage of calories from fat to a greater extent (35.2 vs. 36.1%, P = 0.004), increased servings of fruit per day (1.89 vs. 1.68, P = 0.016), and increased vegetable servings (2.24 vs. 2.06, P = 0.011) but did not decrease weight. However, weight loss for individuals who received the healthy eating intervention and who increased SMBG frequency as recommended was significantly greater, with a 0.26-kg loss in those who remained in a pre-action SMBG stage but a 1.78-kg loss in those performed SMBG as recommended (P <or= 0. 01).\n This study demonstrates that this intervention has the potential of positively impacting the health of broad populations of individuals with diabetes, not just the minority who are ready for change.", "This study assessed stages of change in fat intake, physical activity, and cigarette smoking during a randomized controlled trial of behavioral counseling.\n Twenty general practices (primary health care centers) were randomized to lifestyle counseling by behavioral methods or to usual health promotion. A total of 883 patients were selected for the presence of 1 or more of the following risk factors: cigarette smoking, high cholesterol, or a combination of a high body mass index and low physical activity. Stage of change (precontemplation, contemplation, preparation, and action/maintenance) was assessed at baseline and after 4 and 12 months.\n The odds of moving to action/maintenance for behavioral intervention vs control patients at 4 months were 2.15 (95% confidence interval [CI] = 1.30, 3.56) for fat reduction, 1.89 (95% CI = 1.07, 3.36) for increased physical activity, and 1.77 (95% CI = 0.76, 4.14) for smoking cessation. The likelihood of achieving action/maintenance was related to baseline stage for all 3 behaviors.\n Brief behavioral counseling based on advice matched to stage of readiness for change may be valuable in encouraging healthy lifestyles among patients in primary care at raised risk of cardiovascular disease." ]

[ "16640064" ]

[ "Outcomes of clinical trial: tinnitus masking versus tinnitus retraining therapy." ]

[ "A controlled clinical study was conducted to evaluate prospectively the clinical efficacy of tinnitus masking (TM) and tinnitus retraining therapy (TRT) in military veterans having clinically significant tinnitus. Qualifying patients were placed into the two groups in an alternating manner (to avoid selection bias), and treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of treatment were evaluated using three self-administered tinnitus questionnaires (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index) and the verbally administered TRT interview forms. Findings are presented from the three written questionnaires, and from two of the interview questions (percentage time aware of, and annoyed by, tinnitus). Outcomes were analyzed on an intent-to-treat basis, using a multilevel modeling approach. Of the 123 patients enrolled, 118 were included in the analysis. Both groups showed significant declines (improvements) on these measures, with the TRT decline being significantly greater than for TM. The greater declines in TRT compared to TM occurred most strongly in patients who began treatment with a \"very big\" tinnitus problem. When patients began treatment with a \"moderate\" tinnitus problem, the benefits of TRT compared to TM were more modest." ]

[ "17094744", "6193578" ]

[ "Forced versus minimal intravenous hydration in the management of acute renal colic: a randomized trial.", "Acute ureteral colic and fluid intake." ]

[ "The management of acute renal colic is a problem commonly encountered by both urologists and emergency medicine physicians. The classic approach to managing uncomplicated acute renal colic involves hydration, along with imaging and pain control. Previous studies have suggested that hydration has a significant impact on patient comfort, as well as spontaneous stone passage. This study evaluated the effects of maintenance v forced hydration and its effect on the pain experienced from renal colic.\n Forty male and 18 female patients with a mean age of 41 years suspected to have acute renal colic were identified in the emergency department. After screening and informed consent, the patients were enrolled in the study, and 43 patients were eventually available for analysis. Patients received intravenous (IV) analgesia, imaging with a noncontrast CT scan of abdomen and pelvis, and assignment to either forced IV hydration with 2 L of normal saline over 2 hours (N = 20) or minimal IV hydration at 20 mL of normal saline per hour (N = 23). A visual analog pain scale was completed hourly for a total of 4 hours. Demographic information, laboratory and imaging results, narcotic use in morphine equivalents (ME), and pain scores were recorded and compared. Spontaneous stone passage rates were also calculated by careful patient follow-up. Results were considered statistically significant at p < 0.05.\n Stone size was equivalent in the two treatment groups (p > 0.05). There was no difference in the narcotic requirement in ME (p = 0.644) between the two groups. Similarly, there was no difference in hourly pain score or stone-passage rates between the groups (p > 0.05).\n Treatment of uncomplicated renal colic has traditionally included vigorous intravenous hydration, as well as medications for the control of pain and nausea. Our data suggest that maintenance intravenous fluids are as efficacious as forced hydration with regard to patient pain perception and narcotic use. Moreover, it appears the state of hydration has little impact on stone passage.", "In the treatment of acute ureteral colic opinions differ regarding the consequences of fluid intake. This study was undertaken to evaluate a possible relationship between fluid load and the pain. One group of patients received 3 liters of fluid intravenously, while in another group all fluids were withheld. No intergroup differences as regards pain was found after 6 hours of observation." ]

[ "9576406" ]

[ "A randomized trial of captopril for microalbuminuria in normotensive adults with sickle cell anemia." ]

[ "Nephropathy is a common complication of sickle cell anemia and is often preceded by proteinurea. Our aim was to evaluate the effect of angiotensin-converting enzyme inhibition on microalbuminuria in sickle cell patients.\n We performed a randomized, double-blind, placebo-controlled trial in 22 normotensive patients with sickle cell anemia and persistent microalbuminuria. Patients received captopril (25 mg/day) or placebo and were followed up for 6 months. Albuminuria, blood pressure, and serum creatinine and hemoglobin concentrations were measured at baseline and at 1, 3, and 6 months. The primary outcome variable was the 6-month change in albuminuria between the two groups.\n Baseline albuminuria was 121 (SD 66) mg per 24 hours in the captopril group and 107 (SD 86) mg per 24 hours in the placebo group. Microalbuminuria decreased from baseline in the captopril group but increased in the placebo group. The mean absolute change and the mean percentage change in microalbuminuria were significantly different between the two groups at 6 months (absolute change -45 mg per 24 hours in the captopril group versus +18 mg per 24 hours in the placebo group, P <0.01; and percentage change -37% in the captopril group versus +17% in the placebo group, P <0.01). The 95% confidence intervals (CI) for the difference in albuminuria between the two groups were 63 (CI 40 to 86) mg per 24 hours for the mean absolute change and 54% (CI 22% to 85%) for the mean percentage change. Blood pressure decreased slightly from baseline in captopril-treated patients and did not change in the placebo group. The change was significantly different between the two groups only for diastolic blood pressure at 6 months (P <0.01).\n Captopril reduces albuminuria and slightly decreases blood pressure in patients with sickle cell anemia. More studies are required to demonstrate the sustained benefit on protein excretion." ]

[ "12011193", "17699538", "12495948", "19413910", "16795653", "18835404" ]

[ "\"Walk in to Work Out\": a randomised controlled trial of a self help intervention to promote active commuting.", "Promoting walking to school: results of a quasi-experimental trial.", "Randomised controlled trial of site specific advice on school travel patterns.", "Pilot evaluation of a walking school bus program in a low-income, urban community.", "Multiple incentives in encouraging car pool formation on a university campus.", "Increasing active travel to school: are we on the right track? A cluster randomised controlled trial from Sydney, Australia." ]

[ "Study objective: To determine if a self help intervention, delivered via written interactive materials (the \"Walk in to Work Out\" pack), could increase active commuting behaviour (walking and cycling). Design: Randomised controlled trial. The intervention group received the \"Walk in to Work Out\" pack, which contained written interactive materials based on the transtheoretical model of behaviour change, local information about distances and routes, and safety information. The control group received the pack six months later. Focus groups were also conducted after six months. Setting: Three workplaces in the city of Glasgow, Scotland, UK. Participants: 295 employees who had been identified as thinking about, or doing some irregular, walking or cycling to work. Main results: The intervention group was almost twice as likely to increase walking to work as the control group at six months (odds ratio of 1.93, 95% confidence intervals 1.06 to 3.52). The intervention was not successful at increasing cycling. There were no distance travelled to work, gender, or age influences on the results. Twenty five per cent (95% confidence intervals 17% to 32%) of the intervention group, who received the pack at baseline, were regularly actively commuting at the 12 month follow up. Conclusion: The \"Walk in to Work Out\" pack was successful in increasing walking but not cycling. The environment for cycling must be improved before cycling will become a popular option.", "To assess the impact of a combined intervention on children's travel behaviour, stage of behavioural change and motivations for and barriers to actively commuting to school.\n A quasi-experimental trial involving pre- and post-intervention mapping of routes to school by active and inactive mode of travel and surveys of \"stage of behaviour change\" and motivations for and barriers to actively commuting to school.\n The intervention school participated in a school-based active travel project for one school term. Active travel was integrated into the curriculum and participants used interactive travel-planning resources at home. The control school participated in before and after measurements but did not receive the intervention.\n Two primary schools in Scotland with similar socioeconomic and demographic profiles.\n Two classes of primary 5 children and their families and teachers.\n Post intervention, the mean distance travelled to school by walking by intervention children increased significantly from baseline, from 198 to 772 m (389% increase). In the control group mean distance walked increased from 242 to 285 m (17% increase). The difference between the schools was significant (t (38) = -4.679, p<0.001 (95% confidence interval -315 to -795 m)). Post intervention, the mean distance travelled to school by car by intervention children reduced significantly from baseline, from 2018 to 933 m (57.5% reduction). The mean distance travelled to school by car by control children increased from baseline, from 933 to 947 m (1.5% increase). The difference in the change between schools was significant (t (32) = 4.282, p<0.001 (95% confidence interval 445 to 1255 m)).\n Intervention was effective in achieving an increase in the mean distance travelled by active mode and a reduction in the mean distance travelled by inactive mode on school journey.", "To evaluate the effect of site specific advice from a school travel coordinator on school travel patterns.\n Cluster randomised controlled trial of children attending 21 primary schools in the London boroughs of Camden and Islington. A post-intervention survey measured the proportion of children walking, cycling, or using public transport for travel to school, and the proportion of parents/carers very or quite worried about traffic and abduction. The proportion of schools that developed and implemented travel plans was assessed.\n One year post-intervention, nine of 11 intervention schools and none of 10 control schools had travel plans. Proportions of children walking, cycling, or using public transport on the school journey were similar in intervention and control schools. The proportion of parents who were very or quite worried about traffic danger was similar in the intervention (85%) and control groups (87%). However, after adjusting for baseline and other potential confounding factors we could not exclude the possibility of a modest reduction in parental concern about traffic danger as a result of the intervention.\n Having a school travel coordinator increased the production of school travel plans but there was no evidence that this changed travel patterns or reduced parental fears. Given the uncertainty about effectiveness, the policy of providing school travel coordinators should only be implemented within the context of a randomised controlled trial.", "To evaluate the impact of a walking school bus (WSB) program on student transport in a low-income, urban neighborhood.\n The design was a controlled, quasi-experimental trial with consecutive cross-sectional assessments. The setting was three urban, socioeconomically disadvantaged, public elementary schools (1 intervention vs. 2 controls) in Seattle, Washington, USA. Participants were ethnically diverse students in kindergarten-5th grade (aged 5-11 years). The intervention was a WSB program consisting of a part-time WSB coordinator and parent volunteers. Students' method of transportation to school was assessed by a classroom survey at baseline and one-year follow-up. The Pearson Chi-squared test compared students transported to school at the intervention versus control schools at each time point. Due to multiple testing, we calculated adjusted p-values using the Ryan-Holm stepdown Bonferroni procedure. McNemar's test was used to examine the change from baseline to 12-month follow-up for walking versus all other forms of school transport at the intervention or control schools.\n At baseline, the proportions of students (n = 653) walking to the intervention (20% +/- 2%) or control schools (15% +/- 2%) did not differ (p = 0.39). At 12-month follow up, higher proportions of students (n = 643, p = 0.001)) walked to the intervention (25% +/- 2%) versus the control schools (7% +/- 1%). No significant changes were noted in the proportion of students riding in a car or taking the school bus at baseline or 12-month follow up (all p > 0.05). Comparing baseline to 12-month follow up, the numbers of students who walked to the intervention school increased while the numbers of students who used the other forms of transport did not change (p < 0.0001). In contrast, the numbers of students who walked to the control schools decreased while the numbers of students who used the other forms of transport did not change (p < 0.0001).\n A WSB program is a promising intervention among urban, low-income elementary school students that may promote favorable changes toward active transport to school.\n ClinicalTrials.gov NCT00402701.", "The effects of a combined token economy and reserved parking program were evaluated as a means of increasing car pooling among students on a university campus. Following a baseline period, students in two experimental parking lots were notified of the availability of reserved parking and coupons redeemable for 25 cents in merchandise for each occupant of automobiles containing two or more people. Two control lots also were monitored for a comparison of treatment effects. Results indicated variable increases in car pooling in the two experimental lots and no increase in the control lots. Removal of the 25-cent coupons from one treatment lot (reserved parking only) did not adversely affect rates of car pooling. An analysis of individual automobile occupancy rates among car poolers indicated distinct patterns of car pooling and underscored the importance of individual subject data analysis in the present situation. A cost-benefit analysis indicated that even moderately effective car pool programs can be cost-effective on both a public and personal level.", "To evaluate the effectiveness of a program to increase walking to and from school.\n A cluster randomised controlled trial.\n 24 primary public schools in inner west Sydney, Australia.\n 1996 students aged 10-12 years and their parents.\n A two-year multi-component program included classroom activities, development of school Travel Access Guides, parent newsletters and improving environments with local councils.\n Two measures were used: a survey completed by students on how they travelled to and from school over five days, and a survey completed by their parents on how their child travelled to and from school in a usual week.\n The percentage of students who walked to and from school increased in both the intervention and control schools. Data from parent surveys found that 28.8% of students in the intervention group increased their walking, compared with 19% in the control group (a net increase of 9.8%, p=0.05). However this effect was not evident in the student data.\n The study produced a mixed result, with a high variation in travel patterns from school to school. Intervention research should address the complexity of multiple factors influencing student travel to school with a focus on changing local environments and parents' travel to work." ]

[ "18543483" ]

[ "[Treatment of refractory polycystic ovary syndrome by bushen huoxue method combined with ultrasound-guided follicle aspiration]." ]

[ "To observe the clinical effect of traditional Chinese medicine Bushen Houxue (BSHX) method combined with ultrasound-guided follicle aspiration (MFA) in treating refractory polycystic ovary syndrome (PCOS).\n Forty-four patients with PCOS were randomly assigned to two groups by randomizing digital table, 20 in the observation group and 24 in the control group. MFA was performed on both groups, and the decoction of BSHX, which consisted of dodder seed 20 g, prepared rehmannia root 10 g, mulberry mistletoe 20 g, epimedium 15 g, psoralea fruit 10 g, solomonseal rhizome 10 g, honeylocust thorn 15 g, peach kernel 10 g, pleione bulbocodioides 10 g, red sage root 20 g, and licorice root 6 g, was given to the observation group one dose every day for 14 days every menstrual cycle. Changes of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) were determined before and after MFA. The impacts on quantity of HMG used, number of sinus follicle, mature follicle, incidence of ovarian hyperstimulating syndrome (OHSS), luteinized unrupture follicular syndrome (LUFS) and pregnance rate were also observed.\n MFA had been performed for 42 cycles in the observation group and 56 cycles in the control group. Levels of T, LH and LH/FSH ratio markedly reduced after aspiration, showing significant difference as compared with those of before treatment in both groups (P < 0.01), and difference of LH/FSH between groups was of statistical significance (P <0.01). In the observation group, 18 patients (90.0%) had their sinus follicle decreased to < 10 after MFA, while in the control group, it reached to <10 in 22 patients (91.70%), all were different to those before treatment (P <0.01). In the observation group, the quantity of HMG used for promoting ovulation was (585.0 +/- 195.0) IU, number of mature follicle at the day of HCG injection was 1.1 +/- 0.3, while in the control group, the corresponding data were (1470.0 +/- 532.5) IU and 3.1 +/- 1.4, all with significant difference between groups (P <0.01). None of OHSS and 1 case of LUFS occurred in the former group, while 1 mild OHSS and 2 LUFS in the latter. After ovulation promoting therapy and in the 3-month secutive follow-up period, pregnancy was found in 8 out of the 18 patients in the observation group (one twins and 7 single), with the pregnancy rate of 44.4%; while in the control group, 7 in 22 (2 twins and 5 single) was found, the pregnancy rate being 31.8%.\n BSHX method combined with MFA is a safe and effective treatment for refractory PCOS, with few trauma. The combined usage of Chinese herbal medicine could significantly reduce dosage of HMG used for promoting follicle and the production of multiple mature follicles, thus to avoid the risk of OHSS." ]

[ "18562423", "17526456" ]

[ "Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial.", "Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study." ]

[ "Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.", "Schizophrenia is a devastating psychiatric disorder. Clozapine has long been the gold standard for treatment of patients with treatment-resistant schizophrenia; however, some patients are only partially responsive to clozapine treatment. Augmentation of clozapine treatment might enhance its effectiveness in partial responders, but only a few studies have investigated possible augmentation strategies. This study compared the effectiveness and tolerability of the combination of amisulpride and clozapine with the combination of quetiapine and clozapine in patients who were only partially responsive to clozapine monotherapy. Fifty-six treatment-resistant patients who were partially responsive to clozapine were randomly assigned to receive amisulpride or quetiapine along with an ongoing stable dose of clozapine. Fifty patients completed the study. Patients were evaluated at baseline and at the first, third, sixth, and eighth weeks. Efficacy measures consisted of the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Clinical Global Impression (CGI) scale. Tolerability and adverse effects were assessed with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and the Simpson Angus Scale (SAS). A substantial improvement occurred in both groups by the end of the eighth week; however, the improvement associated with amisulpride was significantly greater than that seen with quetiapine. This difference was noted as early as the third week of follow-up in terms of CGI scores, and by the sixth week with regard to BPRS, SANS, and SAPS scores. Both drugs were well tolerated, as measured by UKU and SAS. Improvement favoring clozapine+amisulpride could be attributed to the selective D2/D3 binding property of amisulpride, which had an additional effect in improving symptoms of schizophrenia. The authors concluded that amisulpride seems to be effective and well tolerated for augmentation purposes in clozapine-resistant patients." ]

[ "9915528", "10528595", "16934640" ]

[ "Increased efficiency and cost-effectiveness in the evaluation of the blunt abdominal trauma patient with the use of ultrasound.", "Prospective evidence of the superiority of a sonography-based algorithm in the assessment of blunt abdominal injury.", "Randomized controlled clinical trial of point-of-care, limited ultrasonography for trauma in the emergency department: the first sonography outcomes assessment program trial." ]

[ "The efficacy and effectiveness of ultrasound (US) in evaluating patients suspected of having blunt abdominal trauma are near that of computed tomography (CT) and diagnostic peritoneal lavage (DPL). Because no cost-effectiveness study has been reported, the purpose of this study was to demonstrate that US is more efficient and cost-effective than CT/DPL in evaluating blunt abdominal trauma. Over a 9-month period, 331 patients suspected of sustaining blunt abdominal trauma were evaluated at a Level I trauma center by US, CT, and/or DPL. Cost data and time to disposition were determined for analysis. The sensitivity, specificity, and accuracy of US were similar to those reported in previous studies. There was a significant difference in time to disposition with the US group being significantly lower (P = 0.001). The total procedural cost was 2.8 times greater for the CT/DPL group than for the US group. US is not only effective in diagnosing blunt abdominal trauma, but it is also more efficient and cost-effective than is CT/DPL.", "Although the routine use of FAST (focused assessment with sonography for trauma) in the evaluation of trauma victims is increasing, to our knowledge, a prospective comparison of contemporary adult trauma victims managed with and without FAST has not been reported in North America.\n Adult victims of blunt trauma for whom there was a suspicion of abdominal injury were managed with one of two diagnostic algorithms, FAST or no-FAST. The two algorithms were compared for diagnostic accuracy, cost, time, and delayed diagnoses.\n Among 706 patients (mean Injury Severity Score, 23), 460 were managed with FAST and 246 with no-FAST. The two groups were similar with respect to age, Injury Severity Score, prehospital time, and mortality (p = not significant). There were 3 of 460 (0.7%) delayed diagnoses in the FAST group and 4 of 246 (1.6%) in the no-FAST group (p = not significant). The diagnostic accuracy for the FAST and no-FAST algorithms was 99% and 98%, respectfully. The FAST and no-FAST algorithms led to similar rates of laparotomy, 13% and 14%, respectfully, but nonoperative management was more common in the no-FAST group (p < 0.01). The mean diagnostic cost for the FAST algorithm was $156, compared with $540 with the no-FAST algorithm (p < 0.0001) and the mean time required for diagnostic work-up was 53 minutes with the FAST algorithm, compared with 151 minutes with the no-FAST algorithm (p < 0.0001).\n This study has provided prospective evidence that a FAST-based algorithm for blunt abdominal injury was more rapid, less expensive, and as accurate as an algorithm that used computed tomography or diagnostic peritoneal lavage only. Trauma centers are encouraged to incorporate a FAST-based algorithm into their initial management of blunt trauma victims.", "Annually, 38 million people are evaluated for trauma, the leading cause of death in persons younger than 45 years. The primary objective is to assess whether using a protocol inclusive of point-of-care, limited ultrasonography (PLUS), compared to usual care (control), among patients presenting to the emergency department (ED) with suspected torso trauma decreased time to operative care.\n The study was a randomized controlled clinical trial conducted during a 6-month period at 2 Level I trauma centers. The intervention was PLUS conducted by verified clinician sonographers. The primary outcome measure was time from ED arrival to transfer to operative care; secondary outcomes included computed tomography (CT) use, length of stay, complications, and charges. Regression models controlled for confounders and analyzed physician-to-physician variability. All analyses were conducted on an intention-to-treat basis. Results are presented as mean, first-quartile, median, and third-quartile, with multiplicative change and 95% confidence intervals (CIs), or percentage with odds ratio and 95% CIs.\n Four hundred forty-four patients with suspected torso trauma were eligible; 136 patients lacked consent, and attending physicians refused enrollment of 46 patients. Two hundred sixty-two patients were enrolled: 135 PLUS patients and 127 controls. There were no important differences between groups. Time to operative care was 64% (48, 76) less for PLUS compared to control patients. PLUS patients underwent fewer CTs (odds ratio 0.16) (0.07, 0.32), spent 27% (1, 46) fewer days in hospital, and had fewer complications (odds ratio 0.16) (0.07, 0.32), and charges were 35% (19, 48) less compared to control.\n A PLUS-inclusive protocol significantly decreased time to operative care in patients with suspected torso trauma, with improved resource use and lower charges." ]

[ "17685739", "3043555", "3013033", "1357701", "9015796", "1868860", "7003639", "2865766" ]

[ "Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study.", "The effect of ceruletide on tardive dyskinesia: a double-blind placebo-controlled study.", "Essential fatty acid supplementation in tardive dyskinesia.", "Treatment of tardive dyskinesia with ceruletide: a double-blind, placebo-controlled study.", "Tardive dyskinesia exacerbated after ingestion of phenylalanine by schizophrenic patients.", "Low doses of insulin as a treatment of tardive dyskinesia: conjuncture or conjecture?", "Failure of lithium treatment in established tardive dyskinesia.", "Estrogen replacement and tardive dyskinesia." ]

[ "Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation.\n The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure.\n The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003).\n Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated.\n ClinicalTrials.gov identifier NCT00190008.", "1. In a double-blind placebo-controlled study of 37 patients with tardive dyskinesia, the therapeutic effect of ceruletide was evaluated. 2. The patients were assigned at random to two groups that received either intramuscular injections of 0.8 micrograms/kg of ceruletide or placebo once weekly for 4 weeks. Conventional neuroleptic medication was not changed 3 weeks prior to and throughout the study period. Tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale over an 8-week period. 3. Ceruletide had a more pronounced effect on TD than the placebo however, because of the limited number of subjects examined, the difference between the two groups was not significant. Ceruletide was more effective than placebo in patients under 60 years of age (p less than 0.05) and whose antipsychotic medication was mainly butyrophenones. 4. No serious side effect was noted. 5. The findings suggested that ceruletide therapeutically benefits patients with tardive dyskinesia.", "Preclinical and clinical observations suggest that enhancement of prostaglandin activity inhibits catecholamine release and may have antidyskinetic effects. A double-blind therapeutic trial with prostaglandin precursor essential fatty acids was conducted in 16 patients with tardive dyskinesia. No beneficial effects were seen.", "The effectiveness of a once-weekly i.m. injection of ceruletide (0.8 microgram/kg) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia (TD) was evaluated in a double-blind, placebo-controlled, matched-pairs study. Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo. Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow, but long-lasting improvement of TD symptoms. Side effects, which were mild and transient, consisted mainly of nausea and epigastric discomfort. The incidence of side effects did not differ between the ceruletide- and placebo-treated groups. Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia.", "Despite continued research, the influences that promote or exacerbate tardive dyskinesia (TD) symptoms remain incompletely understood. Recent findings (Gardos et al. 1992; Richardson et al. 1989) suggest that ingestion of the dietary constituent, phenylalanine, might exacerbate TD symptoms, but a double-blind, placebo-controlled challenge had not previously been conducted in schizophrenic patients. On two different mornings, in counterbalanced order, 18 male schizophrenic patients with TD were challenged with either 100 mg/kg phenylalanine or placebo. Effects on abnormal involuntary movements, recall memory, and plasma phenylalanine were measured 90 minutes post-challenge. The results supported the hypothesis in that involuntary movements increased to a statistically and clinically meaningful degree after the phenylalanine challenge, but not after placebo. No effects on memory were detected. Significant order effects characterized the plasma findings but not the behavioral data. Results indicate that a dietary constituent, the amino acid phenylalanine, can potentially exacerbate tardive dyskinesia symptoms in schizophrenic patients. The influence of phenylalanine and other ingested substances on clinical symptomatology warrants further investigation.", "Tardive dyskinesia (TD) induced by antipsychotic drugs represents a great concern for patients and psychiatrists. Considering its pathophysiological mechanisms, there exists a convergence towards the development of postsynaptic dopaminergic hypersensitivity as a possible cause of TD. Hypersensitivity following receptor blockade is the consequence of an increased number of receptors and such a synthesis is energy-dependent. In the brain, under normal conditions, energy is almost exclusively provided by glucose utilization. We thus hypothesized that, if glucose availability were reduced, the metabolically hyperactive structures should represent the best functional target of a reduction in fuel availability. Twenty chronic schizophrenic outpatients (13 males, 7 females), aged 20-67 (mean: 38.3), accepted to participate in this double-blind, placebo-controlled study. They were randomly assigned to either the insulin treatment group (10 patients) or to the insulin-placebo group (10 patients). They received a subcutaneous injection of 10 units of standard insulin or placebo at 10 a.m. From day 1 to day 15, injections were performed daily and, thereafter, every other week for 5 weeks totalizing 20 injections in 90 days. At day 7, the insulin treatment group showed a sharp decrease in the intensity of TD symptoms which persisted throughout the duration of the study. By contrast, no change in TD symptomatology was observed in the insulin-placebo-treated group. Although a direct effect on DA neurones, or at least the participation of such an effect, cannot be excluded, our data favor a role of decreased glucose availability in reversing receptor hypersensitivity.", "Eleven patients with tardive dyskinesia were treated with lithium carbonate in a placebo-controlled double-blind crossover study. No significant effect of lithium on either tardive dyskinesia or blood prolactin concentrations was demonstrated, but 5 patients developed pseudo-Parkinsonian features.", "A double-blind randomized clinical trial was conducted among 10 post-menopausal women with tardive dyskinesia (TD) to test the effect of estrogen replacement of the severity of abnormal movements and other outcome variables. After 3 weeks of treatment, the mean Abnormal Involuntary Movement Scale (AIMS) score decreased by 38% in the estrogen group and by 9% in the placebo group; the difference between groups was marginally significant (p less than 0.10). However, the small sample size and the imbalance between groups in baseline AIMS scores do not allow us to rule out the confounding effects of other prognostic factors. There were no significant differences between treatment groups for parkinsonian and psychological symptoms at any visit or for changes in these variables between visits. The findings of this preliminary trial are consistent with the results of other human and animal investigations, and they support the need for future research to understand the role of estrogens in the neuropathology and treatment of TD." ]

[ "18556683" ]

[ "Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial." ]

[ "Endometriosis is associated with an inflammatory response. Hence infliximab, an anti-TNF-alpha monoclonal antibody, might relieve pain.\n A randomized placebo-controlled trial was designed with 21 women with severe pain and a rectovaginal nodule of at least 1 cm. After 1 month of observation, three infusions of infliximab (5 mg/kg) or placebo were given. Surgery was performed 3 months later and follow-up continued for 6 months. The primary end-point was pain (dysmenorrhea, deep dyspareunia and non-menstrual pain) rated at each visit by the clinician and on a daily basis by the patient who in addition scored pain by visual analog pain scale and analgesia intake. Secondary end-points included the volume of the endometriotic nodule, pelvic tenderness and the visual appearance of endometriotic lesions at laparoscopy.\n Pain severity decreased during the treatment by 30% in both the placebo (P < 0.001) and infliximab groups (P < 0.001). However, no effect of infliximab was observed for any of the outcome measures. After surgery, pain scores decreased in both groups to less than 20% of the initial value.\n Infliximab appears not to affect pain associated with deep endometriosis. Treatment is associated with an important placebo effect. After surgery, pain decreases to less than 20%. Trials registration number ClinicalTrials.gov: NCT00604864." ]

[ "7658778", "10028980", "17388666" ]

[ "Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial.", "Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group.", "Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe." ]

[ "A randomised trial was done to evaluate the impact of improved sexually transmitted disease (STD) case management at primary health care level on the incidence of HIV infection in the rural Mwanza region of Tanzania. HIV incidence was compared in six intervention communities and six pair-matched comparison communities. A random cohort of about 1000 adults aged 15-54 years from each community was surveyed at baseline and at follow-up 2 years later. Intervention consisted of establishment of an STD reference clinic, staff training, regular supply of drugs, regular supervisory visits to health facilities, and health education about STDs. 12,537 individuals were recruited. Baseline HIV prevalences were 3.8% and 4.4% in the intervention and comparison communities, respectively. At follow-up, 8845 (71%) of the cohort were seen. Of those initially seronegative, the proportions seroconverting over 2 years were 48 of 4149 (1.2%) in the intervention communities and 82 of 4400 (1.9%) in the comparison communities. HIV incidence was consistently lower in the intervention communities in all six matched pairs. Allowing for the community-randomised design and the effects of confounding factors, the estimated risk ratio was 0.58 (95% CI 0.42-0.79, p = 0.007). No change in reported sexual behaviour was observed in either group. We conclude that improved STD treatment reduced HIV incidence by about 40% in this rural population. This is the first randomised trial to demonstrate an impact of a preventive intervention on HIV incidence in a general population.", "The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities.\n This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios.\n The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses.\n We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors.", "HIV-1 control in sub-Saharan Africa requires cost-effective and sustainable programmes that promote behaviour change and reduce cofactor sexually transmitted infections (STIs) at the population and individual levels.\n We measured the feasibility of community-based peer education, free condom distribution, income-generating projects, and clinic-based STI treatment and counselling services and evaluated their impact on the incidence of HIV-1 measured over a 3-y period in a cluster-randomised controlled trial in eastern Zimbabwe. Analysis of primary outcomes was on an intention-to-treat basis. The income-generating projects proved impossible to implement in the prevailing economic climate. Despite greater programme activity and knowledge in the intervention communities, the incidence rate ratio of HIV-1 was 1.27 (95% confidence interval [CI] 0.92-1.75) compared to the control communities. No evidence was found for reduced incidence of self-reported STI symptoms or high-risk sexual behaviour in the intervention communities. Males who attended programme meetings had lower HIV-1 incidence (incidence rate ratio 0.48, 95% CI 0.24-0.98), and fewer men who attended programme meetings reported unprotected sex with casual partners (odds ratio 0.45, 95% CI 0.28-0.75). More male STI patients in the intervention communities reported cessation of symptoms (odds ratio 2.49, 95% CI 1.21-5.12).\n Integrated peer education, condom distribution, and syndromic STI management did not reduce population-level HIV-1 incidence in a declining epidemic, despite reducing HIV-1 incidence in the immediate male target group. Our results highlight the need to assess the community-level impact of interventions that are effective amongst targeted population sub-groups." ]

[ "2679115", "9870617" ]

[ "Placebo effect in surgery for Menière's disease: nine-year follow-up.", "The non-specific effect of endolymphatic sac surgery in treatment of Meniere's disease: a prospective, randomized controlled study comparing \"classic\" endolymphatic sac surgery with the insertion of a ventilating tube in the tympanic membrane." ]

[ "A 9-year follow-up report of our study on endolymphatic shunt procedure versus mastoidectomy is presented. Success has been maintained in about 70% of the patients in both groups and no significant differences between the two groups have been found.", "A prospective, randomized study was carried out comparing the effect of two surgical modalities in the treatment of patients with Meniere's disease: insertion of an endolymphatic sac shunt and insertion of a ventilating tube in the tympanic membrane. A total of 29 patients, 12 males and 17 females, age 27-71 years, were operated on in two ear, nose and throat (ENT) departments. Of these patients, 15 had an endolymphatic shunt inserted and 14 had a ventilating tube inserted in the tympanic membrane. Postoperative follow-up was carried out in the department in which the patients had not been operated. The severity of the disease was scored pre- and postoperatively, and the results evaluated under the guidelines of the Committee on Hearing and Equilibrium (1995) for the diagnosis and evaluation of therapy in Meniere's disease. The patients in both groups had a statistically significant reduction in dizzy spells, measured 6 and 12 months postoperatively, and there was no difference between the groups. The pathophysiological explanation for the reduction in dizzy spells in each of the treatment modalities is debatable and the effect is non-specific. The patients' hearing and tinnitus were statistically unaffected by the treatment in both groups, though 2 patients in the shunt group developed severe hearing loss (anacusis/70 dB)." ]

[ "1761665", "16844491", "8822431", "8458457", "8866392", "1760422", "8299789", "7589657", "15654136", "9895397", "2245833", "10615885" ]

[ "The ESHRE multicentre trial on the treatment of unexplained infertility: a preliminary report. European Society of Human Reproduction and Embryology.", "Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial.", "Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility.", "A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate.", "Superovulation and intrauterine insemination vs. superovulation alone in the treatment of unexplained infertility. A randomized study.", "Gamete intrafallopian transfer (GIFT) compared with intrauterine insemination in the treatment of unexplained infertility.", "Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles.", "Ovulation induction with gonadotropins as sole treatment in infertile couples with open tubes: a randomized prospective comparison between intrauterine insemination and timed vaginal intercourse.", "A randomised prospective trial of intrauterine insemination versus timed intercourse in superovulated cycles with clomiphene.", "Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network.", "A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis.", "Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis." ]

[ "Nineteen European fertility centres participated in a controlled randomized trial aimed at comparing the effectiveness of five methods for the treatment of unexplained infertility. Each centre was invited to employ two of the five treatments being investigated, and the treatment allocated to individual patients was then decided by randomization. The treatments were superovulation alone, and superovulation together with one of the following procedures: intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT), in-vitro fertilization (IVF). All the patients admitted to the study had experienced greater than 36 months infertility prior to the start of the trial, and only patients less than 38 years of age were included in the investigation. Further, the study was confined to patients with normal Fallopian tubes, and where there was evidence of spontaneous ovulation. Yet another prerequisite for inclusion in the study was that the male partner was 'normal' as regards fertility. Due to unavoidable practical difficulties, the experimental design eventually obtained was severely unbalanced. Nevertheless, objective statistical comparisons were possible among the five treatments, using non-orthogonal analyses of variance. By the completion of the trial 444 patients had been treated in a total of 649 cycles. There was some statistical evidence that the pregnancy rate obtained from superovulation alone was inferior to that obtained by using superovulation together with one of the methods of assisted conception.(ABSTRACT TRUNCATED AT 250 WORDS)", "Intrauterine insemination with controlled ovarian hyperstimulation is commonly used as first-line treatment for couples with unexplained subfertility. Since such treatment increases the risk of multiple pregnancy, a couple's chances of achieving an ongoing pregnancy without it should be considered to identify those most likely to benefit from treatment. We aimed to assess the incremental effectiveness of intrauterine insemination with controlled ovarian hyperstimulation compared with expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy.\n 253 couples with unexplained subfertility and a 30-40% probability of a spontaneous ongoing pregnancy within 12 months were randomly assigned either intrauterine insemination with controlled ovarian hyperstimulation for 6 months or expectant management for 6 months. The primary endpoint of this hospital-based study was ongoing pregnancy within 6 months. Analysis was by intention to treat. This trial is registered with the Dutch Trial Register and as an International Standard Randomised Clinical Trial, number ISRCTN72675518.\n Of the 253 couples enrolled, 127 were assigned intrauterine insemination with controlled ovarian hyperstimulation and 126 expectant management. In the intervention group, 42 (33%) women conceived and 29 (23%) pregnancies were ongoing. In the expectant management group, 40 (32%) women conceived and 34 (27%) pregnancies were ongoing (relative risk 0.85, 95% CI 0.63-1.1). There was one twin pregnancy in each study group, and one woman in the intervention group conceived triplets.\n A large beneficial effect of intrauterine insemination with controlled ovarian hyperstimulation in couples with unexplained subfertility and an intermediate prognosis can be excluded. Expectant management for 6 months is therefore justified in these couples.", "The aim of this prospective randomized controlled study was to determine the possible role of ovulation induction with intrauterine insemination (IUI) in the treatment of unexplained infertility. A total of 100 patients were randomized to receive ovulation induction with or without IUI. All patients were treated with long-course gonadotrophin-releasing hormone analogue (GnRHa), starting in the luteal phase, and exogenous follicle stimulating hormone (FSH) to induce follicular growth. Ovulation was induced using human chorionic gonadotrophin and timed intercourse (TI) was advised 24-48 h later or IUI was effected 36-48 h later. Both the cycle fecundities (21.8 and 8.5%) and the cumulative ongoing pregnancy rates after three cycles (42 and 20%) were significantly higher (P < 0.03) in the IUI group than in the TI group respectively. This is a clear indication that ovulation induction with IUI is an effective treatment method for unexplained infertility, but ovulation induction with TI has a negligible impact in this large group of patients.", "To determine the relative efficacy of intrauterine insemination (IUI), direct intraperitoneal insemination, and intercourse in cycles stimulated with clomiphene citrate (CC) or human menopausal gonadotropins (hMG).\n A prospective randomized trial with a 2(3) factorial design with eight different treatment alternatives. Only one cycle per couple was performed.\n The Departments of Obstetrics and Gynecology, Central Hospital, Västerås and Akademiska Hospital, Uppsala University, Uppsala, Sweden.\n Of 157 randomized couples with unexplained infertility including 51 cases with minimal or mild endometriosis, 148 were selected for comparison.\n Pregnancy rate (PR).\n Follicular stimulation with hMG gave a higher PR than with CC in the insemination cycles, 19% (10/52) and 4% (2/49), respectively, but the PRs in intercourse cycles were not significantly different for hMG and CC, 13% (3/24) and 17% (4/23), respectively. Insemination cycles and intercourse cycles had a similar overall PR, 12% (12/101) and 13% (7/47), respectively. Furthermore, IUI and direct intraperitoneal insemination did not differ in efficacy.\n Follicular stimulation with hMG is more effective than CC in insemination cycles, but insemination as such seems to have no beneficial effect on the PR in stimulated cycles for treatment of unexplained infertility.", "To assess whether intrauterine insemination (IUI) improves the fertility rates in women with unexplained infertility.\n We recruited 68 women with unexplained infertility and allocated them randomly to treatment with three to five cycles of superovulation plus IUI (36 patients) or superovulation alone (32 patients). Superovulation was obtained with clomiphene citrate, human menopausal gonadotropins and human chorionic gonadotropins.\n The cycle fecundity rate was 10% in patients who underwent superovulation alone and 19% in those treated with superovulation plus IUI (P < .05).\n Our results demonstrate that superovulation plus IUI is more effective than superovulation alone in the treatment of unexplained infertility.", "To compare GIFT, intrauterine insemination (IUI) with, and without, ovarian hyperstimulation in the treatment of unexplained infertility.\n Women randomly allocated to one of three treatment protocols.\n Northern Regional Fertility Centre.\n 59 couples with unexplained infertility of more than 3 years duration.\n Three cycles of either GIFT, IUI after ovarian hyperstimulation or IUI in a spontaneous cycle.\n Pregnancy resulting in a live birth.\n Fecundabilities were 0.12 after GIFT, 0.018 after ovarian hyperstimulation and IUI, and 0.018 after IUI in a spontaneous cycle. The fecundability after IUI was no different from that which would be expected without treatment in these couples but fecundability was significantly better (P greater than 0.02) after GIFT.\n This trial does not support the use of IUI in the treatment of unexplained infertility but confirms the value of GIFT.", "To test the hypothesis that in couples undergoing IUI, actively managed cycles using clomiphene citrate (CC) stimulation, ultrasound monitoring, and hCG timing will result in increased pregnancy rate (PR) per cycle compared with unstimulated urinary LH-timed cycles.\n Fifty-six couples with unexplained infertility (n = 26) or male factor infertility (n = 30) participated in the study.\n Tertiary academic medical center.\n Prospective, randomized, crossover. Couples were randomized initially to one of the two study groups (treatment A: LH-timed IUI; treatment B: CC-stimulated, hCG-timed IUI). If no pregnancy occurred, each couple alternated between the two regimens during subsequent cycles, up to a total of four cycles.\n Twenty-nine couples completed the study and the analysis of 95 cycles revealed that among the male factor infertility group, one pregnancy occurred during the 26 cycles of each treatment group (PR per cycle of 3.9% for both treatment groups). In contrast, among the unexplained infertility group, there was a marked difference in the effect of treatments. During treatment A only one pregnancy occurred in 20 cycles (PR of 5% per cycle) whereas during treatment B, six pregnancies occurred in 23 cycles (PR of 26.1% per cycle).\n If IUI is chosen as the treatment modality in unexplained infertility, the addition of active ovulation management that includes CC stimulation, ultrasound monitoring of folliculogenesis, and hCG timing of ovulation increases the PR per cycle. In couples with male infertility, PR per cycle is low and is apparently not affected by the addition of active ovulation management.", "To assess if ovulation induction with gonadotropins alone is an appropriate treatment in couples affected by unexplained and mild male factor-related infertility and if the concomitant IUI improves the pregnancy rate (PR).\n Prospective and randomized trial.\n Infertility Centre of Department of Obstetrics and Gynecology of the University of Cagliari, Cagliari, Italy.\n Two hundred couples affected by unexplained or mild male factor-related infertility were assigned randomly to one of two treatment groups: group A (n = 100), treated with three consecutive cycles of ovulation induction with gonadotropins associated with timed vaginal intercourse; group B (n = 100), treated with three consecutive cycles of ovulation induction with gonadotropins associated with IUI.\n Pregnancy rate.\n The PRs obtained with ovulation induction with gonadotropins associated with IUI were similar to those obtained with ovulation induction with gonadotropins associated with timed vaginal intercourse.\n Ovulation induction with gonadotropins alone may be as effective as ovulation induction with gonadotropins associated with IUI in couples with unexplained and mild male factor infertility and can represent the initial treatment option for its minimal invasivity and reduced cost and organizational problems.", "Despite its wide use, the benefits of intrauterine insemination (IUI), its over timed intercourse (TI) in couples with unexplained infertility is a matter of debate. Studies in Indian couples with unexplained infertility showing benefit of IUI over TI are not available. The present study was done with the objective of comparing TI and IUI with husband's sperm in couples with unexplained infertility undergoing superovulation with clomiphene.\n A total of 140 couples with unexplained infertility were subjected to controlled ovarian hyperstimulation (COH) with clomiphene and prospectively randomized to receive either TI (group A) or IUI (group B). Complete follow up was available for 113 couples only.\n The pregnancy rate and cycle fecundity rate after COH/TI was 41 and 8.8 per cent and after COH/IUI 18 and 3.4 per cent respectively. The difference was statistically not significant.\n The findings of the present study showed that in women with unexplained infertility addition of IUI to ovulation induction does not improve conception rates. COH/TI can help to achieve good results and save the expense and discomfort due to a invasive procedure.", "Induction of superovulation with gonadotropins and intrauterine insemination are frequently used to treat infertility. We conducted a large, randomized, controlled clinical trial of these treatments.\n We studied 932 couples in which the woman had no identifiable infertility factor and the man had motile sperm. The couples were randomly assigned to receive intracervical insemination, intrauterine insemination, superovulation and intracervical insemination, or superovulation and intrauterine insemination. Treatment continued for four cycles unless pregnancy was achieved.\n The 231 couples in the group treated with superovulation and intrauterine insemination had a higher rate of pregnancy (33 percent) than the 234 couples in the intrauterine-insemination group (18 percent), the 234 couples in the group treated with superovulation and intracervical insemination (19 percent), or the 233 couples in the intracervical-insemination group (10 percent). Stratified, discrete-time Cox proportional-hazards analysis showed that the couples in the group treated with superovulation and intrauterine insemination were 3.2 times as likely to become pregnant as those in the intracervical-insemination group (95 percent confidence interval, 2.0 to 5.3) and 1.7 times as likely as those in the intrauterine-insemination group (95 percent confidence interval, 1.2 to 2.6). The couples in the intrauterine-insemination group and in the group treated with superovulation and intracervical insemination were nearly twice as likely to conceive as those in the intracervical-insemination group.\n Among infertile couples, treatment with induction of superovulation and intrauterine insemination is three times as likely to result in pregnancy as is intracervical insemination and twice as likely to result in pregnancy as is treatment with either superovulation and intracervical insemination or intrauterine insemination alone.", "This study was initiated to test the hypothesis that treatment with clomiphene citrate (CC) and intrauterine insemination (IUI) results in increased fecundity when compared with periovulatory intercourse in couples with either unexplained infertility or surgically corrected endometriosis. Sixty-seven couples entered a randomized, prospective trial comparing CC/IUI with observation. During the study, there were 14 pregnancies in 148 treated cycles (fecundity = 0.095) compared with 5 pregnancies in 150 untreated cycles (fecundity = 0.033). Using life-table analysis and the log-rank test, the difference in fecundities was statistically significant. Pregnancy outcome was not significantly different between the two groups. When comparing conception with nonconception cycles during treatment, no differences between the size of the lead follicle or the number of dominant follicles was detected. We conclude that treatment with CC/IUI improves fecundity in couples with unexplained infertility or surgically corrected endometriosis.", "Couples affected by idiopathic subfertility or male subfertility have an estimated spontaneous conception rate of about 2% per cycle. Although various infertility treatments are available, counselling of a couple in their choice of treatment is difficult because of the lack of consistent data from good-quality comparative studies. We compared the results of treatment with intrauterine insemination (IUI) with those of in-vitro fertilisation (IVF), and did a cost-effectiveness analysis.\n In a prospective, randomised, parallel trial, 258 couples with idiopathic subfertility or male subfertility were treated for a maximum of six cycles of either IUI in the spontaneous cycle (IUI alone), IUI after mild ovarian hyperstimulation, or IVF. The primary endpoint was a pregnancy resulting in at least one livebirth after treatment. Cost-effectiveness based on real costs was studied by Markov chain analysis.\n 86 couples were assigned IUI alone, 85 IUI plus ovarian hyperstimulation, and 87 IVF. Ten couples dropped out before treatment began. Although the pregnancy rate per cycle was higher in the IVF group than in the IUI groups (12.2% vs 7.4% and 8.7%, respectively; p=0.09), the cumulative pregnancy rate for IVF was not significantly better than that for IUI. Couples in the IVF group were more likely than those in the IUI groups to give up treatment before their maximum of six attempts (37 [42%] drop-outs vs 13 [15%] and 14 [16%], respectively; p<0.01). The woman's age was the only factor that influenced a couple's chance of success. IUI was a more cost-effective treatment than IVF (costs per pregnancy resulting in at least one livebirth 8423-10661 Dutch guilders [US$4511-5710] for IUI vs 27409 Dutch guilders [US$14679] for IVF).\n Couples with idiopathic or male subfertility should be counselled that IUI offers the same likelihood of successful pregnancy as IVF, and is a more cost-effective approach. IUI in the spontaneous cycle carries fewer health risks than does IUI after mild hormonal stimulation and is therefore the first-choice treatment." ]

[ "6349256", "390972", "406212", "6931470", "2870944", "8104468", "3298419", "387151", "6818587", "1096541", "3446307", "3788652" ]

[ "Comparative double-blind study of flupenthixol decanoate and fluphenazine decanoate in the treatment of patients relapsing in a schizophrenic symptomatology.", "A double-blind comparison of flupenthixol decanoate and fluphenazine decanoate in the treatment of chronic schizophrenia.", "Clinical and social comparison of fluphenazine decanoate and flupenthixol decanoate in the community maintenance therapy of schizophrenia.", "Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate.", "A comparative trial of depot pipothiazine.", "The decanoates of flupenthixol and clopenthixol in the treatment of chronic schizophrenic in-patients. Implications for community psychiatry.", "The effects of a 50% reduction of cis(z)-flupenthixol decanoate in chronic schizophrenic patients maintained on a high dose regime.", "High dose flupenthixol decanoate in chronic schizophrenia.", "A depot neuroleptic withdrawal study. Plasma concentration of fluphenazine and flupenthixol and relapse frequency.", "Peroral and parenteral administration of long-acting neuroleptics: a double-blind study of penfluridol compared to flupenthixol decanoate in the treatment of schizophrenia.", "Double-blind comparison of half-dose and standard-dose flupenthixol decanoate in the maintenance treatment of stabilised out-patients with schizophrenia.", "Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison." ]

[ "Thirty-two chronic schizophrenics who had relapsed entered a double-blind randomised study and were followed-up for 2 years with the intention of measuring any difference in therapeutic effect and side effects between flupenthixol decanoate and fluphenazine decanoate. No differences could be seen as regards the global effect or the effect on the schizophrenic symptomatology during the first 6 months. After 1 year of treatment flupenthixol decanoate showed a trend towards a better effect on schizophrenic symptomatology. A corresponding result was seen for the depressive symptoms. There were no differences in the appearance of side effects. The need for additional neuroleptics in the initial phase seemed to be identical for both drugs. A possible slow antipsychotic effect with flupenthixol decanoate is probably due to the administered dose being somewhat low (in the present study approximately 31 mg flupenthixol corresponding to 27 mg fluphenazine). This suggests that flupenthixol should have been given in a somewhat higher dose (25 mg fluphenazine decanoate corresponding to 40 mg flupenthixol decanoate).", "Sixty-four chronic stabilised schizophrenics were studied for 18 months in order to assess the possible difference in therapeutic effects and side effects between flupenthixol decanoate and fluphenazine decanoate. Although certain differences in the BPRS sub-scores in favour of flupenthixol were present at various stages in the study, there was no significant difference between the two drugs in the overall antipsychotic scores at the end of the assessment period; however, more patients on fluphenating required additional therpay for depression or anxiety during the trial period.", "The clinical and social effects of flupenthixol decanoate and fluphenazine decanoate were compared in the maintenance treatment of a population of chronic schizophrenic out-patients over a period of 9 months. The results failed to show significant difference between the treatments, and in particular, reports suggesting specific advantages for flupenthixol decanoate in alleviating the negative symptoms of apathy, anergia and depression in chronic schizophrenics were not confirmed. It seems that chronic schizophrenic patients who are well established on one depot preparation are unlikely to be benefited by being changed to the alternative.", "Clopenthixol decanoate and flupenthixol palmitate, both depot neuroleptics belonging to the thioxanthene group, were studied during double-blind conditions for 12 months using four week intervals between injections. The 60 patients included in the study were chronic schizophrenics and treated as outpatients after earlier admission to hospital and rehabilitation training periods. They had all been treated with depot neuroleptics in the last three years and they had been free from relapse for at least 15 months. The main aim with this trial was to study the two depot drugs during maintenance treatment conditions in an outpatient setting. Ten patients dropped out, 7 because of unsatisfactory effect, mainly because only limited dose levels were accepted according to the design. In spite of the earlier long lasting neuroleptic treatment and the good social adaptation in this schizophrenic subgroup there was observed a symptom decrease in all the rating scales even in these symptom poor patients. This improvement in psychopathology with optimal results after half a year seems to be a combined result of the efficient neuroleptics tested and careful monitoring of the drug.", "Thirty-nine chronic schizophrenic patients were selected for a 12-month double-blind evaluation of the effectiveness of pipothiazine palmitate (PPT) and flupenthixol decanoate (FPX) in the maintenance management of their illness. Allocation was at random and, in order to allow constant injection intervals, the patients typically received every 2 weeks either 40 mg of flupenthixol decanoate or alternating injections of 100 mg of pipothiazine palmitate and placebo. At monthly intervals the patients were assessed using both a battery of rating scales (which included the Brief Psychiatric Rating Scale (BPRS), the Extrapyramidal Symptoms Rating Scale (EPS] and a general side-effects evaluation. At 3-monthly intervals they were also rated on the Comprehensive Psychiatric Rating Scale (CPRS) and the Zung Depression Scale. Haematological and biochemical tests were performed every 3 months. Both drugs provided good control of psychotic symptoms and side-effects were not troublesome. No substantial difference was detected on the CPRS and the Zung scales. There was a trend in favour of PPT on the BPRS survey, detectable at 6 months and reaching statistical significance by 12 months. We conclude that the PPT regime is at least as effective as the FPX treatment and probably more so. It is possible that even longer periods of control could be obtained with PPT.", "Vagrant chronic schizophrenic subjects in a stable untreated state received in-patient treatment with either Flupenthixol decanoate or Clopenthixol decanoate. Both drugs were found to be significantly effective and well tolerated. The apparent better response to Flupenthixol decanoate was seen as dose-dependent. The findings and their implications for Community Psychiatry, particularly in developing countries are discussed.", "Eighteen chronic schizophrenic patients who had shown improvement from increased maintenance dosages of cis(z)-flupenthixol decanoate were entered into a double-blind study in which half of the patients were randomly allocated to be maintained on 50% of their pre-trial dosage. During the 44 week study the reduced dosage group showed increased morbidity and one-third of these patients had a schizophrenic relapse. The greatest deterioration occurred in patients reduced from above to below 200 mg cis(z)-flupenthixol decanoate biweekly. A review of all the patients entered into the study showed a relationship between deterioration of schizophrenic and depressive features and cis(z)-flupenthixol plasma levels which reflected the administered dosage. Prolactin levels in general did not reflect control of schizophrenic symptoms. Side-effects were few, and there was no emergence of tardive dyskinesia. A multicentre trial is needed for further evaluation.", "In a double-blind trial, female 'drug-resistant' chronic schizophrenic in-patients were given high dose or standard dose flupenthixol decanoate for 13 weeks. Plasma flupenthixol levels showed a five-fold interindividual variation, but were consistently higher with the high dose. Analysis of final scores showed no statistically significant differences between groups with regards to mental state, ward behaviour and extrapyramidal side-effects. When compared with pre-trial scores, the extrapyramidal side-effects worsened significantly in the high dose patients and social withdrawal decreased in the standard dose patients. The mental state of a sub-group of patients, possibly drug resistant for pharmacokinetic reasons, improved significantly on the high dose over the 13 weeks.", "A double-blind withdrawal trial in 41 chronic schizophrenic outpatients was carried out during 6 months. Depot neuroleptics (fluphenazine decanoate or flupenthixol decanoate) were compared with placebo to evaluate clinical and neurological effects during continued therapy and during withdrawal. The drugs were significantly more effective than placebo in preventing relapse and rehospitalization. In the placebo group 62% relapsed compared to 27% in the drug group. There was a weak and nonsignificant tendency to a higher relapse frequency in the flupenthixol group compared to the fluphenazine group. After withdrawal for 6 months, plasma levels for fluphenazine were detectable. Plasma levels for flupenthixol were not detectable after 9 weeks of withdrawal. The differences in the plasma levels may possibly explain the difference in relapse rate between the two depot neuroleptics. Furthermore, it was found that the patients who relapsed during fluphenazine treatment had a significantly lower plasma level of the drug than patients who did not relapse during treatment. The results from this study provide some information on the therapeutic levels of fluphenazine and flupenthixol in schizophrenic patients.", "Fifty-six out of 60 schizophrenic patients completed a double-blind study of two long-acting neuroleptics, penfluridol (peroral) and flupenthixol decanoate (parenteral). Half of the patients were on maintenance therapy of flupenthixol prior to the study, the other half on penfluridol. The actual double-blind study (12 weeks) was commenced after a preliminary period of 4 weeks, the patients in the two main groups being randomly divided into two further groups, one continuing the medication unchanged, the other changing to the alternative drug. It was found possible to make a sudden switch from penfluridol to flupenthixol decanoate and vice versa without any significant change in the condition of the patient. The same dosage (in 70% of the patients from 40 to 80 mg) of penfluridol was used per week as was employed for flupenthixol decanoate per fortnight. Changes in the intensity of the symptoms (total Brief Psychiatric Rating Scale (BPRS) score) were moe pronounced in the preliminary period (during unchanged treatment) than on changed medication in the blind period. Both drugs induced approximately the same degree of akathisia, Parkinsonism and autonomic side effects. The practical consequences of equipotent therapeutical effect of a peroral and parenteral long-acting neuroleptic are briefly discussed.", "A double-blind controlled trial of 50% dose reduction in maintenance treatment in stable out-patients with low BPRS scores and good social function shows a significantly higher relapse rate in the low-dose group at 12 months (P less than 0.05). After an interval of 24-36 months from dose reduction, 56-76% had experienced a relapse and 76-79% had resumed their former dosage. No clear advantage was shown for the lower dose in either a reduction of side-effects or improved social function, but a reduced prevalence or lower rate of symptom emergence for tardive dyskinesia was suggested.", "Thirty-two schizophrenic patients, previously treated with antipsychotics, were treated with haloperidol decanoate and flupenthixol decanoate in a double-blind cross-over study. The drugs were given for 24 weeks each at an individually adapted dose. The last three injections of either drug were given at fixed 4-week intervals. The mean dose over the two treatment periods changed from 131 mg (start) to 151 mg (week 24) in the haloperidol decanoate group and from 56 mg to 66 mg in the flupenthixol decanoate group, the inter-drug ratio being 2.3:1. During the first study period, the patients' condition remained rather stable with both drugs. After crossing-over, the symptoms were further reduced with haloperidol decanoate but increased with flupenthixol decanoate. Side effects of the two drugs were comparable and were generally few and mild. It was concluded that 4-week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals." ]

[ "9382120", "1944423", "12825175", "21973", "16941367", "9482293", "15825026", "3545418", "16227328", "3770039", "18585831", "6380367", "3914014", "20723631", "69058", "3608590", "12724480", "3534568" ]

[ "Clinical efficacy of pneumococcal vaccine in the elderly: a randomized, single-blind population-based trial.", "The protective efficacy of polyvalent pneumococcal polysaccharide vaccine.", "Effectiveness of the 23-valent polysaccharide vaccine against invasive pneumococcal disease in Navajo adults.", "Protective efficacy of pneumococcal polysaccharide vaccines.", "Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study.", "Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Swedish Pneumococcal Vaccination Study Group.", "Effectiveness of pneumococcal vaccination for elderly people in Catalonia, Spain: a case-control study.", "Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease.", "Clinical efficacy of anti-pneumococcal vaccination in patients with COPD.", "Placebo controlled pneumococcal immunization in patients with bronchogenic carcinoma.", "Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease.", "A controlled evaluation of the protective efficacy of pneumococcal vaccine for patients at high risk of serious pneumococcal infections.", "[Clinical trial of an antipneumococcal vaccine in elderly subjects living in institutions].", "Effectiveness of pneumococcal polysaccharide vaccine against pneumonia and cost analysis for the elderly who receive seasonal influenza vaccine in Japan.", "Immunisation with a polyvalent pneumococcal vaccine. Reduction of adult respiratory mortality in a New Guinea Highlands community.", "Pneumococcal infection and immunologic response to pneumococcal vaccine in chronic obstructive pulmonary disease. A pilot study.", "Effectiveness of pneumococcal polysaccharide vaccine in older adults.", "Efficacy of pneumococcal vaccine in high-risk patients. Results of a Veterans Administration Cooperative Study." ]

[ "To study the efficacy of pneumococcal capsular polysaccharide vaccine among the elderly by use of a population-based intervention in one township, Varkaus, Eastern Finland.\n A randomized, controlled trial in which elderly inhabitants (aged 60 years or older) of the catchment area were randomized to receive either pneumococcal and influenza vaccines (PI group = vaccinated) or influenza vaccine alone (I group = controls) and offered participation. The response rate was 67.4%. The PI group consisted of 1,364 persons and the I group of 1,473 persons. The vaccinations were performed in the municipal health center in the fall of 1982, and all elderly inhabitants were followed for 3 years for the development of radiologically confirmed pneumonia. Pneumococcal etiology was identified by serological methods.\n The incidence of pneumonia was 18.8 per 1,000 person-years in the PI group (73 pneumonia episodes) and 16.6 per 1,000 person-years in the I group (69 episodes). Pneumococcal etiology was found in 27 episodes in the PI group (incidence 7.0 per 1,000 person-years) and in 36 episodes in the I group (incidence 8.6 per 1,000 person-years). In controls (I group) the incidence of pneumococcal pneumonia was significantly higher among persons with increased risk for contracting pneumonia (19 per 1,000 person-years) than among controls with low risk status (4 per 1,000 person-years). No significant protection from pneumococcal pneumonia was found in the study group as a whole (vaccine efficacy 15%, 95% CI -43% to 50%). However, in persons with medical risk factors for contracting pneumonia, there was a statistically significant protective efficacy of 59% (95% CI, 6% to 82%).\n Pneumococcal vaccination significantly reduced the incidence of pneumococcal pneumonia in elderly persons at increased risk for contracting pneumonia. This increased/high-risk category comprised 34% of the population aged 60 years or older. Because targeted vaccination of this large group may be difficult to organize in an efficient manner, vaccinating all elderly persons may be the best strategy to prevent this rather common and often fatal disease.", "Although the protective efficacy of pneumococcal polysaccharide vaccine has been demonstrated in randomized trials in young African gold miners, there has been controversy about its efficacy in older Americans at risk for serious pneumococcal infections. To assess the vaccine's protective efficacy against invasive pneumococcal infections, we conducted a hospital-based case-control study of the efficacy of pneumococcal vaccine in adults with a condition recognized to be an indication for receiving the vaccine.\n From 1984 to 1990, adults in whom Streptococcus pneumoniae was isolated from any normally sterile site were identified by prospective surveillance in the microbiology laboratories of 11 large hospitals; those with an indication for pneumococcal vaccine were enrolled as case patients. For each case patient, one control was matched according to age, underlying illness, and site of hospitalization. We contacted all providers of medical care to ascertain each subject's history of immunization with pneumococcal vaccine. Isolates of S. pneumoniae were serotyped by an investigator unaware of the subject's vaccination history.\n Thirteen percent of the 1,054 case patients and 20 percent of the 1,054 matched controls had received pneumococcal vaccine (P less than 0.001). When vaccine was given in either its 14-valent or its 23-valent form, its aggregate protective efficacy (calculated as a percentage: 1 minus the odds ratio of having been vaccinated times 100) against infections caused by the serotypes represented in the vaccine was 56 percent (95 percent confidence interval, 42 percent to 67 percent; P less than 0.00001) for all 983 patients infected with a serotype represented in the vaccine, 61 percent for a subgroup of 808 immunocompetent patients (95 percent confidence interval, 47 percent to 72 percent; P less than 0.00001), and 21 percent for a subgroup of 175 immunocompromised patients (95 percent confidence interval, -55 percent to 60 percent; P = 0.48). The vaccine was not efficacious against infections caused by serotypes not represented in the vaccine (protective efficacy, -73 percent; 95 percent confidence interval, -263 percent to 18 percent; P = 0.15).\n Polyvalent pneumococcal vaccine is efficacious in preventing invasive pneumococcal infections in immunocompetent patients with indications for its administration. This vaccine should be used more widely.", "Invasive pneumococcal disease occurs 2-3-fold more often among Navajo adults than among adults in the general United States population. The objective of this observational study was to determine the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) among Navajo adults. Active surveillance identified cases of invasive pneumococcal disease during 1996-1997. Three control patients per case patient were matched according to underlying medical conditions, sex, age, and location of medical care. Effectiveness was calculated by regression analysis of case-control sets and by indirect cohort methodology. Diabetes and alcoholism occurred in 41% and 43% of 108 case patients, respectively; 62% of case patients and 64% of control patients were immunized. Overall vaccine effectiveness was 26% (95% confidence interval [CI], -29% to 58%); 15% (95% CI, -116% to 67%) for patients with diabetes and -5% (95% CI, -141% to 54%) for patients with alcoholism. Overall vaccine effectiveness, as determined by use of the indirect cohort methodology, was 35% (95% CI, -33% to 69%). PPV23 was not significantly effective among Navajo adults and may be inadequate to prevent serious pneumococcal disease in this population.", "Clinical studies of 6- and 12-valent pneumococcal capsular polysaccharide vaccines were carried out in controlled studies among novice gold miners in South Africa. In the studies 1,523 persons received pneumococcal vaccine, and 3,171 were included as controls. In the great majority of subjects given pneumococcal vaccine, antibodies developed against the capsular types included in the vaccine. The 6-valent vaccine afforded 76% reduction in cases of laboratory-verified pneumococcal pneumonia caused by the homologous types, and there was 92% reduction in the cases afforded by the 12-valent vaccine. The vaccines were well tolerated and offer great promise for effective control of illnesses caused by pneumococci.", "The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended for elderly persons and persons who are at high risk of infection. However, the effectiveness of the 23-valent PPV remains controversial. We assessed the effectiveness of this vaccine in older adults.\n A prospective cohort study was conducted from January 2002 through April 2005; it included all community-dwelling individuals aged >or=65 years who were assigned to 1 of 8 primary health care centers in Tarragona, Spain (11,241 subjects). The primary outcomes were invasive pneumococcal disease, pneumococcal pneumonia, overall pneumonia rate, and death due to pneumonia. All cases were validated by a check of the clinical records. The association between pneumococcal vaccination and the risk of each outcome was evaluated by means of multivariate Cox proportional hazard models, adjusted for age, sex, comorbidity, immunocompetence, and influenza vaccine status.\n Pneumococcal vaccination was associated with significant reductions in the risk of hospitalization for pneumonia (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.59-0.92) and in the overall pneumonia rate (HR, 0.79; 95% CI, 0.64-0.98). The incidence of invasive pneumococcal disease was low (64 cases per 100,000 person-years), and a considerable protective effect against invasive pneumococcal disease did not attain statistical significance (HR, 0.60; 95% CI, 0.22-1.65). However, the vaccine showed a significant effectiveness of 45% to prevent pneumococcal pneumonia (HR, 0.55; 95% CI, 0.34-0.88). Finally, vaccination was associated with a significant 59% reduction in the risk of death due to pneumonia among vaccinated subjects (HR, 0.41; 95% CI, 0.23-0.72).\n These results indicate that the 23-valent PPV effectively prevented pneumococcal pneumonia (with or without bacteremia) and decreased the rates of overall pneumonia and of mortality due to pneumonia in older adults, providing new arguments for systematic vaccination in the elderly population.", "We assessed the effectiveness of a 23-valent pneumococcal vaccine in the prevention of pneumococcal pneumonia and of pneumonia overall in non-immunocompromised middle-aged and elderly people.\n The prospective, multicentre, double-blind, randomised, placebo-controlled trial was carried out across departments of infectious diseases at six tertiary-care or university hospitals in Sweden. 691 non-immunocompromised patients aged 50-85 years who had been treated as inpatients for community-acquired pneumonia (CAP) were randomly assigned either 23-valent pneumococcal capsular polysaccharide vaccine or placebo (sodium chloride). We used Cox regression models to estimate the relative risks of pneumonia overall and pneumococcal pneumonia for the placebo group compared with the vaccine group.\n 63 (19%) of 339 patients in the vaccine group and 57 (16%) of 352 patients in the placebo group developed a new pneumonia, corresponding to a relative risk over time for the placebo group compared with the vaccine group of 0.83 (95% CI 0.58-1.12, p=0.31). Pneumococcal pneumonia was diagnosed in 16 (4.5%) patients in the placebo group and in 19 (5.6%) in the vaccine group, corresponding to a relative risk for the placebo group of 0.78 (95% CI 0.40-1.51, p=0.45). We found no difference in the death rate between the two study groups.\n The 23-valent pneumococcal polysaccharide vaccine did not prevent pneumonia overall or pneumococcal pneumonia in middle-aged and elderly individuals.", "Observational studies offer an approach to evaluating the effectiveness of vaccination programs. We evaluated the effectiveness of a 23-valent pneumococcal vaccination program for elderly people in Catalonia, Spain, in a matched-set case-control study.\n We identified 149 cases of invasive pneumococcal disease among patients aged > or =65 years who were hospitalized in 12 large hospitals in Catalonia during the period of 1 January 2001 through 31 March 2002. We selected 2 hospital control patients and 1 outpatient control subject for each case patient, matching on the basis of age and underlying medical conditions. We obtained their pneumococcal vaccination histories and used conditional logistic regression to determine effectiveness of vaccination.\n Among all 149 cases of invasive pneumococcal disease, 131 (87.9%) were caused by vaccine or vaccine-related serotypes. In the adjusted analysis, overall effectiveness of vaccination against infections due to all serotypes was 70% (95% confidence interval [CI], 48%-82%). Among immunocompetent subjects with or without high-risk conditions, effectiveness of vaccination was 76% (95% CI, 51%-88%), but among immunocompromised subjects it was 50% (95% CI, -44% to 82%). Among subjects with infections due to vaccine or vaccine-related serotypes, effectiveness of vaccination was 72% (95% CI, 50%-85%) overall and 78% (95% CI, 50%-90%) in those who were immunocompetent, but it was only 46% (95% CI, -54% to 81%) in those who were immunocompromised. Overall effectiveness of vaccination was 65% (95% CI, 35%-81%) during the noninfluenza period.\n Pneumococcal vaccination was effective in preventing invasive pneumococcal disease among all elderly persons in Catalonia. Effectiveness was greater in immunocompetent persons, most of whom had underlying high-risk conditions. The number of subjects was too small to determine whether vaccination was effective in those who were immunocompromised.", "Although pneumococcal vaccine has been recommended for patients with chronic obstructive pulmonary disease (COPD), its efficacy in this population has not been shown. A double-blind randomized controlled trial of 14-valent pneumococcal vaccine was carried out in 189 men and women aged 40 to 89 years with a clinical diagnosis of COPD and a forced expiratory volume in 1 second of less than 1.5 L. Of the 189, 92 received the vaccine and 97 received saline placebo. In a randomly chosen subsample of those who received the vaccine the mean titres of specific IgG antibody to selected pneumococcal polysaccharide serotypes increased two- to threefold by 4 weeks after vaccination. Over a 2-year period the rates of death, hospital admissions and emergency visits and the mean length of hospital stay were not significantly different in the two groups. Although a protective effect of 14-valent pneumococcal vaccine could not be shown, the small size of the sample and the relatively low follow-up rates preclude firm conclusions about efficacy from these data alone. The elevated antibody levels before vaccination in some of the patients, suggesting prior infection with Diplococcus pneumoniae, may partly explain the findings.", "A study was undertaken to evaluate the clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV) in immunocompetent patients with chronic obstructive pulmonary disease (COPD).\n A randomised controlled trial was carried out in 596 patients with COPD of mean (SD) age 65.8 (9.7) years, 298 of whom received PPV. The main outcome was radiographically proven community acquired pneumonia (CAP) of pneumococcal or unknown aetiology after a mean period of 979 days (range 20-1454).\n There were 58 first episodes of CAP caused by pneumococcus or of unknown aetiology, 25 in the intervention group and 33 in the non-intervention group. Kaplan-Meier survival curves for CAP did not show significant differences between the intervention and non-intervention arms (log rank test = 1.15, p = 0.28) in the whole group of patients. The efficacy of PPV in all patients was 24% (95% CI -24 to 54; p = 0.333). In the subgroup aged <65 years the efficacy of PPV was 76% (95% CI 20 to 93; p = 0.013), while in those with severe functional obstruction (forced expiratory volume in 1 second <40%) it was 48% (95% CI -7 to 80; p = 0.076). In younger patients with severe airflow obstruction the efficacy was 91% (95% CI 35 to 99; p = 0.002). There were only five cases of non-bacteraemic pneumococcal CAP, all in the non-intervention group (log rank test = 5.03; p = 0.025). Multivariate analysis gave a hazard ratio for unknown and pneumococcal CAP in the vaccinated group, adjusted for age, of 0.20 (95% CI 0.06 to 0.68; p = 0.01).\n PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction. No differences were found among the other groups of patients with COPD.", "Pneumococcal vaccine [heptadecavalent types 1, 2, 3, 4, 6A, 7F, 8, 9N, 11A, 12F, 14, 15F, 17F, 18C, 19F, 23F and 25 pneumococcal capsular polysaccharide vaccine (Moniarix)] or placebo were evaluated in 26 and 21 patients with bronchogenic carcinoma, most of whom did not receive prior radiotherapy or chemotherapy. No difference was detected as far as clinical outcome is concerned: 3 vaccinated patients out of 26 (11.5%) developed pneumococcal infections (1 fatal bacteremia) and 4/21 (19%) of those who received a placebo presented such an infection (1 fatal bacteremia). The antibody response was significantly increased in the vaccines for types 1, 2, 7F, 8, 9N, 12F, 14, 17F, 18C, 23F and 25.", "To determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV+IV group (n=87) or an IV group (n=80). The number of patients with CLD experiencing infectious acute exacerbation (P=0.022), but not pneumonia (P=0.284), was significantly lower in the PV+IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P=0.037). In patients with CLD, the Kaplan-Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P=0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P=0.019), but not during the second year (P=0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period.", "The protective efficacy of pneumococcal vaccine against systemic pneumococcal infections in adults with the current indications for the vaccine was evaluated in a case-control study. Six (7%) of the 90 cases and 16 (18%) of the matched controls had received pneumococcal vaccine for an odds ratio of 0.33 (p less than 0.05). The vaccine's protective efficacy was 67%, which remained virtually unchanged after adjusting for potential confounding variables. The vaccine's efficacy was 77% for patients at moderately increased risk of pneumococcal infections, but 0% for patients who were severely immunocompromised. The vaccine's protective efficacy was 70% (p less than 0.05) for all patients 55 years or older after controlling for indications for the vaccine in addition to age. Pneumococcal vaccine confers substantial protection against systemic pneumococcal infections on the elderly and patients with illnesses associated with a moderately increased risk of pneumococcal infections.", "Pneumococcal vaccine effectiveness was assessed in a randomized trial among 1,686 old people (mean age: 74, standard deviation: 4 years) living in 24 geriatric hospitals and 26 homes for the aged in our district; 937 were vaccinated with Merck-Sharp and Dohme pneumococcal vaccine (14 serotypes). The 749 others composed the reference group. This study was performed during 2 years, since December 1980. Both groups were randomized after a two-criteria stratification: by clinical risk assessed before the study, and by type of homes for the aged. Forty pneumonias were diagnosed, with 13 proved pneumococcal etiology. The incidence of pneumonia was significantly reduced in the vaccinated group (p less than 10(-4) but the mortality rate was not modified. We concluded in favor of the effectiveness of pneumococcal vaccine: etiological fraction 77.1% (51.2%-89.3% confidence limits, 95% risk) in the population we studied. The incidence of pneumococcal-proved pneumonia was not significantly reduced.", "To determine the clinical efficacy and cost-saving effect of pneumococcal polysaccharide vaccine (PPV) against community-acquired pneumonia (CAP), an open-label, randomized clinical trial was conducted involving 786 Japanese subjects older than 65 years of age receiving a routine influenza vaccine during the 2-year period. Study subjects were randomly assigned to either a PPV group (n=394) or to a non-PPV group (n=392). The incidence, admission and the medical cost for all-cause pneumonia were compared between these two groups. PPV vaccination significantly reduced the incidence of admission for all-cause pneumonia for subjects older than 75 years of age (41.5%, P=0.039) and for those who had difficulty walking (62.7%, P=0.005), but not for all study subjects older than 65 years of age (P=0.183), for the 2-year period. The Kaplan-Meier survival curves for subjects who had difficulty walking free from all-cause pneumonia demonstrated a significant difference (P=0.0146) between the two groups. PPV vaccination significantly reduced medical costs for all study subjects during the first year period (P=0.027). Our present data demonstrated that PPV was effective for all-cause pneumonia for study subjects older than 75 years of age, although the effect was not significant for all study subjects older than 65 years of age.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "A double-blind controlled trial of a 14-valent pneumococcal polysaccharide vaccine was carried out in 11 958 adults at Tari in the Papua New Guinea Highlands. Pneumococcal infection, confirmed by blood-culture and lung aspirate, was less in the vaccinated group by 84%. Mortality from pneumonia was less by 44%.", "We assessed the importance of Streptococcus pneumoniae and immunologic response to 14-valent pneumococcal vaccine in a randomized (saline placebo or vaccine) double-blind pilot study involving 103 patients with chronic obstructive pulmonary disease (COPD). Antibody titers, the flora of the sputum, respiratory infections or pneumonias, and deaths were monitored. The patients' antibody titers before immunization were higher than healthy control subjects. Titers rose normally in those vaccinated but declined more rapidly. Differences between the group receiving placebo and vaccine were not significant at 12 and 24 months. The incidence of pneumonia was high before and after vaccine (47/1,000 vs 41/1,000 patient-years). Nonpneumococcal causes predominated (73 percent of pneumonias; 83.4 percent of lethal pneumonias). Isolates from sputum were predominantly nonvaccine types (50 to 62.5 percent). Twenty-seven patients died; pneumonia occurred in six (one pneumococcal in a vaccinated patient) as a terminal complication of other diseases. Thus, although pneumonia occurred frequently in these patients with COPD and contributed to mortality in 22 percent (six) of the 27 deaths, the predominance of nonpneumococcal causes and the data on antibodies and sputum suggest that pneumococcal vaccine may not be as beneficial for patients with COPD as was hoped. More observations are needed.", "Streptococcus pneumoniae is the chief cause of pneumonia in older adults, but it remains unclear whether use of the pneumococcal polysaccharide vaccine alters the overall risk of community-acquired pneumonia. In a large population of older adults, we assessed the effectiveness of the pneumococcal vaccine.\n In this retrospective cohort study, 47,365 Group Health Cooperative members 65 years of age or older were assessed over a three-year period. The primary outcomes were hospitalization because of community-acquired pneumonia (validated by chart review), pneumonia in patients who were not hospitalized (\"outpatient pneumonia,\" determined from administrative data sources), and pneumococcal bacteremia. The association between pneumococcal vaccination and the risk of each outcome was evaluated by means of multivariate Cox proportional-hazards models, with adjustment for age, sex, nursing-home residence or nonresidence, smoking status, medical conditions, and receipt or nonreceipt of influenza vaccine.\n During the study period, 1428 cohort members were hospitalized with community-acquired pneumonia, 3061 were assigned a diagnosis of outpatient pneumonia, and 61 had pneumococcal bacteremia. Receipt of the pneumococcal vaccine was associated with a significant reduction in the risk of pneumococcal bacteremia (hazard ratio, 0.56; 95 percent confidence interval, 0.33 to 0.93) but a slightly increased risk of hospitalization for pneumonia (hazard ratio, 1.14; 95 percent confidence interval, 1.02 to 1.28). Pneumococcal vaccination did not alter the risk of outpatient pneumonia (hazard ratio, 1.04; 95 percent confidence interval, 0.96 to 1.13) or of any case of community-acquired pneumonia, whether or not it required hospitalization (hazard ratio, 1.07; 95 percent confidence interval, 0.99 to 1.14).\n These findings support the effectiveness of the pneumococcal polysaccharide vaccine for the prevention of bacteremia, but they suggest that alternative strategies are needed to prevent nonbacteremic pneumonia, which is a more common manifestation of pneumococcal infection in elderly persons.\n Copyright 2003 Massachusetts Medical Society", "We conducted a randomized, double-blind, placebo-controlled trial to test the efficacy of the 14-valent pneumococcal capsular polysaccharide vaccine in 2295 high-risk patients (patients with one or more of the following: age above 55 years and the presence of chronic cardiac, pulmonary, renal, or hepatic disease, alcoholism, or diabetes mellitus). Seventy-one episodes of proved or probable pneumococcal pneumonia or bronchitis occurred among 63 of the patients (27 placebo recipients and 36 vaccine recipients). Vaccine-serotype Streptococcus pneumoniae strains were recovered in association with 11 infections in the placebo group and 14 infections in the vaccine group. Pneumococcal infections occurred most frequently among patients with chronic pulmonary, cardiac, or renal diseases. Among vaccine recipients who subsequently had vaccine-type pneumonia or bronchitis, the majority did not make or sustain serum antibodies against their infecting organism in concentrations that were twice as high as the base-line values, or more than 400 ng of antibody nitrogen per milliliter, although their base-line levels were higher than those in subjects in whom infection did not develop. We were unable to demonstrate any efficacy of the pneumococcal vaccine in preventing pneumonia or bronchitis in this population. Our data suggest that chronically ill patients, who are most susceptible to infection, may have an impaired immune response to the pneumococcal vaccine." ]

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[ "Effectiveness of a glass ionomer cement used as a pit and fissure sealant in recently erupted permanent first molars.", "A clinical trial to evaluate the retention of a silver cermet-ionomer cement used as a fissure sealant.", "Caries-preventive effect of a one-time application of composite resin and glass ionomer sealants after 5 years.", "Comparing the caries-preventive effect of two fissure sealing modalities in public health care: a single application of glass ionomer and a routine resin-based sealant programme. A randomized split-mouth clinical trial.", "Evaluation of resin based and glass ionomer based sealants placed with or without tooth preparation-a two year clinical trial.", "Caries-preventive efficacy and retention of a resin-modified glass ionomer cement and a resin-based fissure sealant: a 3-year split-mouth randomised clinical trial.", "Fissure sealants: a 4-year clinical trial comparing an experimental glass polyalkenoate cement with a bis glycidyl methacrylate resin used as fissure sealants.", "A comparison of retention and the effect on caries of fissure sealing with a glass-ionomer and a resin-based sealant.", "Sealant and fluoride varnish in caries: a randomized trial.", "Clinical and antibacterial effectiveness of three different sealant materials.", "Clinical evaluation of FUJI VII sealant material.", "Retention and caries preventive effects of a GIC and a resin-based fissure sealant.", "A three-year follow-up of glass ionomer cement and resin fissure sealants.", "Effect of a nonrinse conditioner on the durability of a polyacid-modified resin composite fissure sealant.", "Clinical effectiveness of an autopolymerized fissure sealant after 2 years.", "A comparative study of two pit and fissure sealants: two-year results in Augusta, Ga.", "A study of pit and fissure sealing in the School Dental Service.", "Retention of a glass ionomer cement and a resin-based fissure sealant and effect on carious outcome after 7 years.", "Randomized trial on fluorides and sealants for fissure caries prevention.", "Caries-preventive effect of sealants produced with altered glass-ionomer materials, after 2 years.", "The effectiveness of a chemically polymerized sealant in preventing occlusal caries: two year results.", "Fissure sealing with a light-cured resin-reinforced glass-ionomer cement (Vitrebond) compared with a resin sealant.", "Clinical evaluation of glass-ionomer/resin-based hybrid materials used as pit and fissure sealants.", "Clinical evaluation of a polyacid-modified resin composite-based fissure sealant: two-year results.", "Clinical evaluation of three different materials used as pit and fissure sealant: 24-months results.", "Benefit from sealants in a moderately fluoridated community.", "Occlusal caries prevention in high and low risk schoolchildren. A clinical trial.", "Clinical success and potential failure after single application of a pit and fissure sealant: a four-year report.", "The effect of operator variability and patient age on the retention of fissure sealant resin.", "Effects of glass ionomer cement, resin-based pit and fissure sealant and HF applications on occlusal caries in a developing country field trial.", "Effectiveness of pit and fissure sealants in the prevention of caries.", "A comparative study of fluoride-releasing composite resin and glass ionomer materials used as fissure sealants." ]

[ "This study's purpose was to evaluate the caries-preventive effect of a glass ionomer cement (GIC) used as an occlusal sealant on recently erupted permanent first molars.\n A double-blind, randomized, controlled, clinical trial was undertaken that included 36 5- to 8-year-olds (and 92 permanent first molars) who were randomly allocated to the test group (GIC) or the control group (auto-polymerized resin-based sealant [RBS]). The Mann-Whitney test was used to compare the number of new carious or filled occlusal surfaces in the 2 groups.\n After 6 months, 1 occlusal surface in the test group and 2 occlusal surfaces in the control group showed carious lesions (P=.15). In the fifth year of follow-up, 2 occlusal surfaces in the test group and 7 occlusal surfaces in the control group were filled or carious (P=.42), and the mean number of sealed surfaces that became carious or filled was 0.2 (95% confidence interval [CI]=0.02-0.70) for the GIC-sealed teeth and 0.6 (95% CI=0.20-1.30) for the RBS-sealed teeth (P=.30).\n High-viscosity glass ionomer cement can provide some level of protection against dental caries when used as a dental sealant in newly erupted permanent first molars.", "A randomized clinical trial was under-taken to compare the retention of a silver cermet-ionomer cement, Ketac Silver, with a conventional, autopolymerizing BIS-GMA resin sealant, Delton, using matched pairs of fissure sites within each subject's mouth. One hundred twenty matched contralateral pairs of fissure sites in first and second permanent molars of 53 school children were sealed with the two materials. The choice of site and material was selected at random. The ages of the children ranged from five to 16 years; first permanent molars were sealed in the five- to 10-year age group, and second permanent molars in the 11- to 16-year age group. Sealants were assessed as present, partly present, or absent at 6, 12, and 24 months. The number of pairs of sites available for reassessment declined from 102 at six months to 59 at 24 months as patients were lost to the study. Retention rates were higher for the Ketac Silver sealants at all three inspection intervals (P < 0.01): 93% compared with 74% at six months, 81% compared with 65% at 12 months, and 83% compared with 58% at 24 months. When analyzed according to age range, the difference between the retention rates was statistically significant in the five- to 10-year-olds but not significant in the 11- to 16-year-olds. The conclusion reached in this study was that cermet cement was better retained than conventional resin sealants in younger children.", "The aim of the present trial was to (1) compare the caries-preventive effect of glass ionomer sealants, placed according to the atraumatic restorative treatment (ART) procedure, with composite resin sealants over time and (2) investigate the caries-preventive effect after complete disappearance of sealant material. Forty-six boys and 57 girls, mean age 7.8 years, were randomly divided into two treatment groups in a parallel-group study design. A light-polymerized composite resin sealant material and a high-viscosity glass ionomer were each placed in 180 fully erupted first molars in their respective treatment groups. Evaluation took place annually for 5 years by calibrated examiners. After 5 years, 86% composite resin and 88% glass ionomer sealants did not survive. Three categories of re-exposure periods for caries development in pits and fissures after complete loss of sealants were distinguished: 0-1, 1-2 and 2-3 years. In the 2- to 3-year group, 13 and 3% of pits and fissures previously sealed with composite resin and glass ionomer, respectively, were diagnosed as having developed a dentine lesion. The relative risks (95% CI) of dentine lesion development in surfaces sealed with glass ionomer compared to those sealed with composite resin after 3, 4 and 5 years were 0.22 (0.06-0.82), 0.32 (0.14-0.73) and 0.28 (0.13-0.61), respectively. The relative risks of dentine lesion development in pits and fissures previously sealed with glass ionomer compared with composite resin over re-exposure periods of 1-2 and 2-3 years were 0.26 (0.14-0.48) and 0.25 (0.09-0.68), respectively. We conclude that the caries-preventive effect of high-viscosity glass ionomer sealants, placed using the ART procedure, was between 3.1 and 4.5 times higher than that of composite resin sealants after 3-5 years. Furthermore, high-viscosity (ART) glass ionomer sealants appear to have a four times higher chance of preventing caries development in re-exposed pits and fissures of occlusal surfaces in first molars than light-cured composite resin sealant material over a 1- to 3-year period. A well-designed clinical trial using different types of oral health personnel should be implemented to confirm these initial results.", "The aim of this study was to compare the caries-preventive effect of two types of sealant modalities and to evaluate whether the caries-preventive effect is related to sealant retention. A hypothesis was tested in which a glass ionomer sealant, once applied to the occlusal surface, was able to protect the fissure from caries even if the sealant appeared lost at visual inspection.\n A 3-year randomized split-mouth trial evaluating two sealant modalities was performed at a public health centre in Finland. A chemically curing glass ionomer cement (GIC) and light-curing resin-based (RB) sealant material were applied randomly to the permanent second molars. Sealant application as a routine treatment procedure was carried out to 599 children in the age group of 12-16 years. Caries rate of the sealed teeth and sealant retention with both materials were analysed by a modified McNemar's test. The effectiveness, rate difference, and relative risk with both sealant materials were measured.\n The difference in caries rate between the two modalities was highly significant. When compared to the GIC sealant method, the effectiveness of RB sealant method was 74.1% and the rate difference 3.2% (95% CI 1.44%, 4.98%). The relative risk for RB-sealed surfaces vs. GIC-sealed surfaces of having detectable dentin caries was 0.26 (95% CI 0.12, 0.57). The retention rate of sealants was higher with RB than GIC (P < 0.001). The effectiveness of the retention rate for RB sealants was 94.8% and the rate difference 87.2% (95% CI 83.86%, 90.50%). The relative risk during the 3-year study period of having a defective or lost RB sealant was 0.052 (95% CI 0.036, 0.075) when compared to having a defective or lost GIC sealant.\n It is concluded that in preventing dentin caries a RB sealant programme including resealing when necessary was more effective than a single application of GIC. The original hypothesis was thus falsified.", "The purpose of this study was to compare the two year clinical performance of two fissure sealants, placed with and without tooth preparation.\n A total of 25 children, between 6-10 years of age, had sealants placed and evaluated for two years at six monthly intervals. All the four first permanent molars of each patient were used in split mouth design and subjected to two different sealants with and without tooth preparation. Teeth were evaluated for defects, retention and development of caries.\n Among the teeth subjected to preparation, 60% of those sealed with glass ionomers and 32% of those sealed with resin sealants showed total loss of sealants at the end of two years. Among the teeth sealed with no preparation, 100% of those sealed with glass ionomers and 80% of those sealed with resin showed total loss. Resin based sealants offered better long term retention compared to glass ionomer-based fissure sealants. Tooth preparation improved the retention of sealants irrespective of the material used. Highest retention was seen in resin sealants with tooth preparation, and lowest retention was seen in glass ionomer-based sealants without preparation. There was a significant increase in caries in teeth sealed after preparation with either material. Teeth sealed with resin sealants exhibited significantly higher caries development compared to teeth sealed with glass ionomers.\n In the current study, resin-based sealants were found to be superior to glass ionomer-based sealants, and tooth preparation improved retention. Loss of sealants seemed to predispose tooth to development of caries, especially in cases where teeth preparation was done.", "This prospective clinical trial compared the retention rate and caries-preventive efficacy of two types of sealant modalities over a 3-year period.\n Using a split-mouth randomised design, 1280 sealants were randomly applied on sound permanent second molars of 320 young patients aged between 12 and 16 years. Half of the teeth (n = 640) were sealed with a resin-modified glass ionomer cement (RMGIC) (Vitremer™, 3M ESPE) and the other half (n = 640) with a conventional light-cure, resin-based fissure sealant (LCRB) (Fluoroshield®, Dentsply Caulk). Teeth were evaluated at baseline, 6-, 12-, 18-, 24-, 30- and 36-month intervals with regard to retention and new caries development.\n On the sealed occlusal surfaces after 3 years, 5.10% of RMGIC and 91.08% of LCRB sealants were totally intact and 6.37% of RMGIC and 7.65% of LCRB sealants were partially intact. New caries lesions were found in 20.06% of RMGIC sealed occlusal surfaces, compared to 8.91% for LCRB sealants.\n The findings of the present clinical study suggest that RMGIC should be used only as a transitional sealant that can be applied to newly erupting teeth throughout the eruptive process, whereas LCRB sealants are used to successfully prevent occlusal caries lesions once an effective rubber dam can be achieved. It can be concluded that there are differences between the RMGIC and LCRB sealants over a 3-year period in terms of the retention rate and caries-preventive efficacy. RMGIC can serve as a simple and economic sealing solution, however provisional. Due to its poor retention rate, periodic recalls are necessary, even after 6 months, to eventually replace the lost sealant.", "The 4-year results of a fissure sealant trial are reported. Glass polyalkenoate and bis GMA sealant were applied to 590 first permanent molar teeth using a half mouth study design in a group of 228 6-8-year-old children. Similar cariostasis was observed for the two materials at the end of 4 years despite marked differences in retention. Polyalkenoate cements probably should be regarded as 'fluoride depot' materials rather than fissure sealants when used in this context.", "To compare the retention and the caries preventive effect of a glass-ionomer developed for fissure sealing (Fuji III) and a chemically polymerized resin-based fissure sealant (Delton).\n A split mouth randomized design using contralateral teeth.\n WHO Regional Demonstration, Training and Research Center for Oral Health, Damascus, Syrian Arab Republic.\n 179 children, 7 years old at the start of the study, were recruited from schools close to the Center. Only children with at least one pair of permanent first molars that were caries free or only had incipient lesions were included in the study. Follow-up examinations for sealant retention were done after 6 months, 1 year, 2 years and 3 years. The number of children available for reexamination was 129 (after 6 months); 121 (after 1 year); 115 (after 2 years) and 116 (after 3 years). Four dental hygienists were trained in the sealant procedures and did approximately one fourth of the sealants each.\n After 3 years the glass-ionomer sealant was completely lost in almost 90% of the teeth compared to less than 10% of the resin sealed teeth. After 3 years the relative risk of a tooth sealed with glass-ionomer over that of a tooth sealed with resin was 3.38 (95% CL: 1.98; 5.79). This finding was consistent over type of tooth.\n The glass-ionomer sealant tested in the present study had poorer retention and less caries protective effect than the resin-based sealant used.", "Little is known about the effect of discontinuation of sealant or fluoride varnish. The purpose of this study was to compare sealant with fluoride varnish in the prevention of occlusal caries in permanent first molars of children over a nine-year period: 4 yrs for program evaluation plus 5 yrs of discontinuation. A clinical trial was conducted on three groups of six- to eight-year-old schoolchildren: a control group (n = 45); a group (n = 37) in which sealant was applied and reapplied up to 36 mos; and a group (n = 38) in which fluoride varnish was applied and re-applied up to 42 mos. Percent caries reduction was studied in these initially healthy molars with complete occlusal eruption: 129 (control), 113 (sealant), and 129 (varnish) molars met inclusion criteria. Of these, 76.7%, 26.6%, and 55.8% had developed occlusal caries at 9 yrs, which implies caries reductions of 65.4% (SE = 8.5%) for sealants vs. control and 27.3% (SE = 10.2%) for varnish vs. control. Furthermore, the varnish program was not effective during the discontinuation period.", "The aim of this work is to study and compare the retention rate, caries-preventing and antibacterial effects of resin-modified glass ionomer and flowable composite in comparison to conventional fissure sealant.\n Forty-five children aged 7-10 years with newly erupted lower first permanent molars were randomly divided into three equal treatment groups. Group I: sealed by a conventional resin sealant; Group II: sealed by resin modified glass ionomer (RMGI); and Group III: sealed by flowable composite. Retention and caries status of the sealed teeth were recorded after 1 month, 6 months, year and 2 years. In addition, Streptococcus mutans counts were assessed at baseline, 1 day, 1 month, 6 months, 1 year and 2 years after sealant application. Data were analyzed by Fisher exact, chi-square and ANOVA tests.\n Group III and Group I showed significantly higher retention rates than Group II fissure sealant (p<0.05). There were no differences of the caries-preventive effects between the tested sealant materials throughout the duration of the study. Streptococcus mutans counts were significantly lower in group II compared to group I or group III up to 6 months of the study (p<0.05). After 1 year of the study the differences of Streptococcus mutans counts were not significant (p>0.05).\n This study indicated a lower retention of RMGI compared to flowable composite and resin sealant without significant difference in caries prevention or long-term bacterial inhibition.", "200 children of the age groups of 3-5 years and 6-7 years were selected for sealant application, each consisting of 100 children. The clinical retention of Fuji VII was tested in both primary and permanent molar teeth at time intervals of 6 months, 12 months and 24 months follow-up and compared with a resin based sealant, Concise. Results demonstrated that there was no difference in the performance of the materials in primary and permanent teeth.", "nan", "The aim of the present study was to compare intraindividually a type III fissure-sealant, glass ionomer cement with a resin-based sealant. One hundred and forty-eight first permanent molars were sealed in forty-seven children. After three years 20.8 percent of the resin and 34.7 percent of the glass ionomer cement sealants were partially lost, and 0 percent and 37.5 percent, respectively, were totally lost. One tooth (1.4 percent) in the glass ionomer cement group and three teeth (4.2 percent) in the resin group developed caries.", "The aim of this study was to evaluate the effect of the simplified conditioning on durability of polyacid-modified resin composite (PMRC; Dyract Seal) fissure sealants. The effectiveness of a nonrinsing conditioner (NRC) on retention of PMRC sealants (92) was studied in a split-mouth design.\n The enamel of 1 molar was pretreated with NRC and coated with Prime & Bond NT (Dentsply DeTrey, Konstanz, Germany)/PMRC. The contralateral molar was conditioned with 36% phosphoric acid and sealed with Delton. The sealant retention was evaluated during 2 years. In addition 49 pairs were sealed with Prime & Bond NT/PMRC after conditioning with 36% phosphoric acid and evaluated after 1 year.\n Significantly higher loss rates at 1 and 2 years were observed for the NRC/Prime & Bond NT/PMRC sealants. At 2 years, partial and total loss rates for Delton were 23% and 11%, and for NRC/Prime & Bond NT/PMRC sealants were 44% and 40%, respectively. At 1 year, phosphoric acid-conditioned Prime & Bond NT/PMRC sealants showed significantly better retention than the NRC-conditioned PMRC sealants and the phosphoric acid-conditioned Delton sealants.\n Conditioning with NRC prior to sealant application cannot be recommended.", "The clinical effectiveness of Delton fissure sealant was studied in 205 children, ages 6--10 years (mean age 71/2). 993 children in grades 1, 2, 3 and 4 were screened and subjects were selected if there was evidence of previous dental caries in the mouth, and a pair of contralateral maxillary or mandibular first permanent molar teeth were free of caries. Two pedodontists independently examined the children in a mobile van equipped with two operatories, and each applied sealants to approximately half of the subjects. After 11 months, in 186 subjects there were 10 sealants partially lost, five experimental teeth carious or filled and 53 control teeth carious or filled. After 24 months, in 175 subjects there were four sealants completely lost, 12 sealants partially lost, 11 experimental teeth carious or filled and 89 control teeth carious or filled. Consequently, sealant retention was 92% after 11 months and 85% after 24 months. Percent effectiveness in caries reduction was 90% after 11 months and 88% after 2 years.", "Two pit and fissure sealants, an autopolymerized unfilled resin, and an ultraviolet-light-curing unfilled resin, applied to the permanent first molars of children are compared in terms of retention and efficacy.", "nan", "The aim of this study was to compare the retention and caries preventive efficacy of glass ionomer (Fuji III; GIC) and light-cured resin-based (Delton; LCR) fissure sealants. One hundred and sixty-six 5-14-year-old schoolchildren received sealants on their newly erupted first or second molars; a split mouth design was used. Previously reported 2-year results showed low retention rates for GIC sealants, but no difference in the caries increment between the groups. The same persons were invited to a dental check-up 6.1 to 7.8 (mean 7.1) years after the application of sealants; 111 persons (66.8% of the original group) participated in the study. The retention of sealants, and the caries status of occlusal surfaces and adjacent proximal surfaces was recorded. On the sealed occlusal surfaces, 10% of GIC and 45% of LCR sealants were totally and 9% of GIC and 20% of LCR sealants partially present. Twenty-three (23.5%) of the occlusal surfaces sealed with GIC and 16 (16.5%) of those sealed with LCR were carious or filled. Compared to LCR sealants, the effectiveness of GIC sealants was -44% (95% CI -71%, -16%) and net gain -7% (95% CI -18%, 4%). The relative risk of caries occurring was 1.44 (95% CI 0.96, 2.14).", "To investigate the effectiveness of topical fluorides in preventing fissure caries, we conducted a randomized controlled trial with parallel groups. In total, 501 children (1,539 molars, 3,078 sites), mean age 9.1 years, who had at least one sound permanent first molar with deep fissures or fissures with signs of early caries were recruited. They were randomly allocated among four groups: (1) resin sealant, single placement; (2) 5% NaF varnish, semi-annual application; (3) 38% silver diamine fluoride (SDF) solution, annual application; and (4) placebo control. Follow-up examinations were conducted every 6 months by a masked examiner. After 24 months, 485 children (97%) were examined. Proportions of pit/fissure sites with dentin caries in the sealant, NaF, SDF, and control groups were 1.6%, 2.4%, 2.2%, and 4.6%, respectively. A multi-level logistic regression analysis accounting for the effects of data clustering and confounding factors showed that fissures in any of the three treatment groups had significantly lower risks of carious cavity development into dentin than did controls (p < 0.05). We concluded that placement of resin sealant, semi-annual application of NaF varnish, and annual application of SDF solution are all effective in preventing pit and fissure caries in permanent molars (ClinicalTrials.gov number CT01446107).", "The aim of the present study was to investigate the caries-preventive effect of sealants produced with a high-viscosity glass-ionomer with an elevated powder-liquid ratio (ART), of having energy added to this glass-ionomer, and that of glass-carbomer, in comparison to that of resin composite sealants.\n The randomized controlled trial covered 407 children, with a mean age of 8 years. At a school compound three dentists placed sealants in pits and fissures of high caries-risk children. Evaluation by two independent evaluators was conducted after 0.5, 1 and 2 years. The Kaplan-Meier survival method, ANOVA and t-test were used in analyzing the data.\n 1352 first permanent molars were sealed. 6.6% of children and 6.8% of sealants dropped out within 2 years. 27 re-exposed pits and fissures, 20 in occlusal and 7 in smooth surfaces, in 25 children, developed a dentin carious lesion. The cumulative survival of dentin carious lesion-free pits and fissures in the glass-carbomer sealant group was statistically significantly lower (97.4%) than those in the high-viscosity glass-ionomer with energy supplied (99%) and the resin-composite (98.9%) sealant groups. There was no statistically significant difference in the cumulative survival of dentin carious lesion-free pits and fissures, between the high-viscosity glass-ionomer with (99%) and without (98.3%) energy supplied sealant groups, after 2 years.\n The survival of dentin carious lesion-free pits and fissures was high in all sealant types. More dentin carious lesions were observed in the glass-carbomer sealant group.\n Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.", "nan", "The aims of the present study were to evaluate the retention and caries-preventive effect of a single application of a light-cured resin-reinforced glass-ionomer cement (Vitrebond) in pits and fissures of newly erupted permanent first and second molars, when compared with a single application of a resin-based sealant (Concise White Sealant) during a 3-year period. The study group comprised 73 pairs of contralateral newly erupted permanent first and second molars (136 fissure sites) in 53 children (29 girls, 24 boys). A split-mouth experimental design was used in which the two sealants were randomly allocated to one of the teeth within each pair. Acid etching was not used before application of the glass-ionomer cement. The sealed teeth were checked for retention and caries after 1, 6, 12, 24 and 36 months. The resin-based sealant was almost totally retained after 3 years (97%) and there was no caries in these teeth. The glass-ionomer cement was increasingly lost and could be observed in only 9% of the sealed sites after 3 years. Carious lesions developed in 10 (7.4%) sites (nine teeth, seven children). It was concluded that the resin-based sealant is superior to the glass-ionomer cement in preventing caries, and that the superior retention of the resin probably is an important factor for this.", "The objective of the present study was to clinically evaluate the hybrid materials Vitremer and Dyract when used as pit and fissure sealants.\n The materials were applied in pairs on the mandibular permanent first molars of 100 children, 7 to 8 years old.\n After 12 months of sealing, the clinical evaluation presented rates of 95.9% and 85.7% of complete retention for Dyract and Vitremer, respectively, indicating a statistically significant difference. The hybrid materials presented a statistically significant protective effect against caries compared with the control group at 6 and 12 months.\n The hybrid materials were able to control occlusal caries.", "A 24-month clinical study was carried out to evaluate and compare the retention rate, marginal integrity and caries preventing effects of a polyacid-modified resin composite based fissure sealant, Dyract Seal, to that of a resin based fluoride fissure sealant, Delton FS+. Fifty-three patients (27 female and 26 male), 7 to 10 years old, were included in the study. At baseline, a total of 192 permanent first molars were sealed with either fissure sealant (n=96, each), using invasive technique. The sealed teeth were evaluated at post-operative 3, 6, 12 and 24 months with respect to evaluation parameters. The data were analyzed with the Chi-Square tests where alpha=0.05. There were no statistically significant differences between fissure sealants as regards to retention and prevention of caries for all periods of the evaluation (p>0.05). However, regarding marginal integrity of the sealants, Delton FS+ gave significantly better results than Dyract Seal for the 3-, 6- and 12-month evaluations, respectively (p<0.05). In conclusion, the use of Dyract Seal on permanent molars with invasive technique was found to be clinically comparable to Delton FS+ for the 24-month evaluation period.", "To evaluate the retention and caries experience effects of three different materials used as fissure sealants after 24 months of clinical application: a resin-modified glass ionomer cement (A), a flowable resin composite (B) and a compomer (C). One hundred and seventeen (117) teeth were sealed with material A, 119 teeth with material B and 120 teeth with material C. Children were randomly assigned. Each one received only one of the materials studied. Plaque index, dmft score and socioeconomic level were scored at baseline. The clinical exams were conducted 6, 12 and 24 months after application of the sealant. Statistical analysis (Kruskal-Wallis) revealed that there were statistically significant differences between the retention rates of groups A and B and between groups B and C after 2 years, with material B showing better results. After 2 years, 3.1% of the teeth of group A, 4.3% of group B and 6.7% of group C were Carious+Filled. There was no evidence of association between caries presence after 2 years and plaque index, dmft score and socioeconomic level. These results suggest that flowable resin composite had a satisfactory retention after this period of evaluation and all three materials were effective on occlusal caries prevention.", "nan", "To evaluate the caries-preventive effect of a resin-modified glass-ionomer cement used as occlusal sealant (Vitremer) compared with fluoride varnish (Duraphat) application on occlusal surfaces of permanent first molars (OSPFM) in 6-8 year-old schoolchildren (n=268) at high (HR) and low (LR) caries risk.\n The children were followed-up for 24 months after being systematically allocated into six groups as follows: Control Groups HRC and LRC: children receiving oral health education (OHE) every 3 months; Groups HRV and LRV: children receiving OHE plus varnish application biannually; and Groups HRS and LRS: children receiving OHE plus a single sealant application . The baseline and follow-up examinations were performed by the same calibrated dentist under natural light, using CPI probes and mirrors, after toothbrushing and air-drying. The DMFS was used to record dental caries, in addition to the detection of initial lesions (IL). Data analysis was performed with two primary outcome measures: DMF and DMF+ IL on the OSPFM.\n After 24 months, only the HRS group showed statistically lower DMF and DMF+IL increments on OSPFM compared with HRC group. HRV group did not differ from HRC and HRS groups. For LR groups, no statistical difference (P> 0.05) was observed among the treatments.", "A single application of a filled chemically initiated BIS-GMA sealant to permanent first molars of children ranging in age from 5 to 8 years covered the original sites in 52.4% of the 185 teeth examined after four years. Retention of sealant is greater in mandibular (64.7%) than in maxillary (42.0%) molars. The rate of loss of sealant was greatest during the first year (20%), then less than 10% per year at the second, third, and fourth recalls. In comparison with two similar studies, the retention of sealant was 20% to 30% greater. Using the parameters of percent effectiveness, net gain, and DMF scores per 100 test and control teeth, the data from the current study indicate a continued positive effect substantially greater than that in other similar studies. Complete loss of sealant does not appear to predispose that surface to caries any more than its contralateral paired surface. However, a partial loss of sealant because of abrasive wear that results in the exposure of the terminal ends of a fissure is a potential failure in that it creates an environment conducive to caries. Thus, even the well-applied sealant does not necessarily constitute permanent obturation of pits and fissures. Periodic clinical observation is necessary to determine the success or potential failure of the sealant treatment.", "nan", "The aim of this community-oriented study was to evaluate different methods to prevent fissure caries. The following products and measures were tested: 1) glass ionomer cement (GIC) applied by dentist; 2) same material applied by short term (3 days) trained personnel (teachers); 3) application of a 0.5% HF solution three times; 4) an established autopolymerized resin based sealant (Delton). The study was performed in Bangkok, Thailand, a city in a developing country experiencing increasing caries prevalence. Children with at least three sound permanent molars from two age groups, 7-8 and 12-13-yr-olds respectively were chosen from very low to medium socioeconomic level families. 1264 children were systematically assigned to experiment or control groups based on school and DMFT. For the younger age group, the 2 yr mean DFS occlusal increment in the Control group was 0.66 surfaces. Significantly lower increments were observed in the GIC experimental group: 0.17 surfaces applied by the teachers and 0.32 applied by dentist, corresponding to 74% and 52% reductions, respectively. The mean increment in the HF group was 0.44 surfaces, a 33% reduction in relation to the Control group. For the 12-13-yr-olds, the mean occlusal surface DF increment was 0.70 surfaces in the Control group. Almost no occlusal increment was found in the Delton group, 0.05 DFS, a 93% reduction. In the GIC Dentist group, the DFS increment was 0.48 and in the Teacher group 0.56, corresponding to 31% and 20% reduction, respectively. A slight and nonsignificant increase of caries in relation to the Control group was observed in the HF group.(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "The objectives of the study were to investigate the clinical use of two fluoride-releasing fissure sealants and to study fluoride release under laboratory conditions.\n In the clinical part of the study the two materials, FluroShield and Baseline, were applied to matched contralateral caries-free first permanent molars in 86 children aged 7-8 years. In the laboratory study fluoride release from each material was measured using a model cavity system.\n After 3 years FluroShield was intact on 70% of teeth. Retention was significantly better on lower molars than upper molars. Baseline was lost from all except two teeth within 6 months. After 3 years, caries had affected four teeth sealed with FluroShield and 24 teeth sealed with Baseline; this difference was highly significant. The laboratory study showed that FluroShield released twice as much fluoride over 9 days than did Baseline. Long term studies using FluroShield showed a small steady fluoride release over 6 months.\n The conclusion of the study was that FluroShield was a much more effective fissure sealant than Baseline. The clinical performance of FluroShield was comparable to that of other inert composite resin sealants and superior to that of fluoride-releasing sealants used previously." ]

[ "1727960", "9310565", "9723823", "9450711" ]

[ "Factors influencing publication of research results. Follow-up of applications submitted to two institutional review boards.", "Publication bias: evidence of delayed publication in a cohort study of clinical research projects.", "Bias in reporting clinical trials.", "Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials." ]

[ "--To investigate factors associated with the publication of research findings, in particular, the association between \"significant\" results and publication.\n --Follow-up study.\n --Studies approved in 1980 or prior to 1980 by the two institutional review boards that serve The Johns Hopkins Health Institutions--one that serves the School of Medicine and Hospital and the other that serves the School of Hygiene and Public Health.\n --A total of 737 studies were followed up.\n --Of the studies for which analyses had been reported as having been performed at the time of interview, 81% from the School of Medicine and Hospital and 66% from the School of Hygiene and Public Health had been published. Publication was not associated with sample size, presence of a comparison group, or type of study (eg, observational study vs clinical trial). External funding and multiple data collection sites were positively associated with publication. There was evidence of publication bias in that for both institutional review boards there was an association between results reported to be significant and publication (adjusted odds ratio, 2.54; 95% confidence interval, 1.63 to 3.94). Contrary to popular opinion, publication bias originates primarily with investigators, not journal editors: only six of the 124 studies not published were reported to have been rejected for publication.\n --There is a statistically significant association between significant results and publication.", "To determine the extent to which publication is influenced by study outcome.\n A cohort of studies submitted to a hospital ethics committee over 10 years were examined retrospectively by reviewing the protocols and by questionnaire. The primary method of analysis was Cox's proportional hazards model.\n University hospital, Sydney, Australia.\n 748 eligible studies submitted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988.\n Time to publication.\n Response to the questionnaire was received for 520 (70%) of the eligible studies. Of the 218 studies analysed with tests of significance, those with positive results (P < 0.05) were much more likely to be published than those with negative results (P > or = 0.10) (hazard ratio 2.32 (95% confidence interval 1.47 to 3.66), P = 0.0003), with a significantly shorter time to publication (median 4.8 v 8.0 years). This finding was even stronger for the group of 130 clinical trials (hazard ratio 3.13 (1.76 to 5.58). P = 0.0001), with median times to publication of 4.7 and 8.0 years respectively. These results were not materially changed after adjusting for other significant predictors of publication. Studies with indefinite conclusions (0.05 < or = P < 0.10) tended to have an even lower publication rate and longer time to publication than studies with negative results (hazard ratio 0.39 (0.13 to 1.12), P = 0.08). For the 103 studies in which outcome was rated qualitatively, there was no clear cut evidence of publication bias, although the number of studies in this group was not large.\n This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor. The study results support the need for prospective registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking systematic reviews.", "The primary aim of the present study was to identify possible occurrence of selective reporting of the results of clinical trials to the Finnish National Agency for Medicines. Selective reporting may lead to poorly informed action or inaction by regulatory authorities.\n In 1987, 274 clinical drug trials were notified to the Finnish National Agency for Medicines. By December 1993, final reports had been received from 68 of these trials and statements that the trial had been suspended from 24 trials. The sponsors of the non-reported trials were requested to report the outcome. The outcomes, if any, of all reported and non-reported trials were classified as positive, inconclusive or negative.\n The total number of trials with positive, inconclusive or negative outcome were 111, 33 and 44, respectively; the outcomes of 86 trials could not be assessed. Final reports were received from 42/111 (38%) trials with positive, 6/33 (18%) with inconclusive and 9/44 (20%) with negative outcomes.\n Substantial evidence of selective reporting was detected, since trials with positive outcome resulted more often in submission of final report to regulatory authority than those with inconclusive or negative outcomes.", "Medical evidence may be biased over time if completion and publication of randomized efficacy trials are delayed when results are not statistically significant.\n To evaluate whether the time to completion and the time to publication of randomized phase 2 and phase 3 trials are affected by the statistical significance of results and to describe the natural history of such trials.\n Prospective cohort of randomized efficacy trials conducted by 2 trialist groups from 1986 to 1996.\n Multicenter trial groups in human immunodeficiency virus infection sponsored by the National Institutes of Health.\n A total of 109 efficacy trials (total enrollment, 43708 patients).\n Time from start of enrollment to completion of follow-up and time from completion of follow-up to peer-reviewed publication assessed with survival analysis.\n The median time from start of enrollment to publication was 5.5 years and was substantially longer for negative trials than for results favoring an experimental arm (6.5 vs 4.3 years, respectively; P<.001; hazard ratio for time to publication for positive vs negative trials, 3.7; 95% confidence interval [CI], 1.8-7.7). This difference was mostly attributable to differences in the time from completion to publication (median, 3.0 vs 1.7 years for negative vs positive trials; P<.001). On average, trials with significant results favoring any arm completed follow-up slightly earlier than trials with nonsignificant results (median, 2.3 vs 2.5 years; P=.045), but long-protracted trials often had low event rates and failed to reach statistical significance, while trials that were terminated early had significant results. Positive trials were submitted for publication significantly more rapidly after completion than were negative trials (median, 1.0 vs 1.6 years; P=.001) and were published more rapidly after submission (median, 0.8 vs 1.1 years; P=.04).\n Among randomized efficacy trials, there is a time lag in the publication of negative findings that occurs mostly after the completion of the trial follow-up." ]

[ "2205286" ]

[ "The implications of introducing the symphyseal-fundal height-measurement. A prospective randomized controlled trial." ]

[ "A total of 1639 women attending the antenatal clinic of Gentofte University Hospital, Copenhagen, during 1986-1987 was randomized into a symphyseal fundal (SF)-group and a control group. The women in the SF-group had their fundal height measured from the 29th week until delivery. The measurements were used along with the other usual screening procedures. The SF-measurements were not found helpful in the prediction of small-for-gestational-age infants and no significant differences were found between the two groups regarding the number of interventions, additional diagnostic procedures, or the condition of the newborns." ]

[ "15686063", "12017833", "10151841", "15112007", "10155878", "15237660", "8153968", "15746218", "8571154", "8356485", "11477970", "12135994", "12973646", "1354792" ]

[ "The impact of user fee exemption on service utilization and treatment seeking behaviour: the case of malaria in Sudan.", "User charges and utilisation of obstetric services in the National Capital District, Papua New Guinea.", "The impact of alternative cost recovery schemes on access and equity in Niger.", "Discontinuation of cost sharing in Uganda.", "The fall and rise of cost sharing in Kenya: the impact of phased implementation.", "Impact of increasing consultation fees on malaria in Africa.", "The need for quasi-experimental methodology to evaluate pricing effects.", "Abolition of cost-sharing is pro-poor: evidence from Uganda.", "Impact of user charges on vulnerable groups: the case of Kibwezi in rural Kenya.", "User fees plus quality equals improved access to health care: results of a field experiment in Cameroon.", "Effect of removing user fees on attendance for curative and preventive primary health care services in rural South Africa.", "The impact of price changes on demand for family planning and reproductive health services in Ecuador.", "Fees-for-services, cost recovery, and equity in a district of Burkina Faso operating the Bamako Initiative.", "Impact of user fees on attendance at a referral centre for sexually transmitted diseases in Kenya." ]

[ "This experimental study was undertaken to assess the effect of different levels of exemption, 25%, 50% and 75%, from health centre user fees on health service utilization and treatment seeking behaviour for malaria by a high risk group of pregnant women and children under 5 years. These are groups in need of special medical attention to prevent progression of the disease into complicated or severe malaria. Sinnar State, one of Sudan's highly endemic malaria regions, was selected to be the experimental area. Exemptions were introduced for one year in six health centres. Two centres for each exemption level, and a further two health centres without exemptions were studied. At the beginning and the end of the trial year, households surveys were conducted in the catchment areas of the health centres, and focus group discussions with pregnant women and mothers of children under 5 years were conducted. Routine data were reviewed for malaria cases in the health centres and six studies on malaria cases were done upon exit from the health centres. In-depth interviews with health staff of the health centres were conducted. Exemption from user fees increased health services utilization, improved treatment-seeking behaviour and promoted early diagnosis. The changes during the experimental year were the largest in the centres with the largest exemption. Therefore, policy changes towards exemptions are necessary to facilitate early diagnosis and treatment of malaria.", "This cross-sectional study examined user charges on the utilization of obstetric services in the 4 urban clinics and antenatal and postnatal wards of the Port Moresby General Hospital (PMGH) in the National Capital District, Papua New Guinea. Analysis of previous records showed attendance to antenatal clinics on first visits declined by 30% soon after the introduction of use charges. However, the frequency of attendances increased and stabilized 12 months after the introduction of the user fees. The mean age for the 482 mothers interviewed was 25 years (range = 15-46 years, SD = 5.3). Over 50% of mothers were between 15-24 years of age and 47% over 24 years. 98.6% were married and a small proportion were single and divorcees (1.4%). Over 85% of mothers had some formal education while 15% without. The frequency of hospital deliveries did not change despite increased in user charges in the PMGH delivery and postnatal care services. Twenty four percent of mothers interviewed indicated they were unable to pay user fees. Mothers unable to pay the user charges were those without income or whose spouses were without regular income. In 23.2% of mothers with some income, majority indicated ability to pay the user fees. There was a minority group of mothers without income but relied heavily on their spouses income to meet the user fees. Mothers living in households with some income were twice more likely (OR = 2.18, 95% CI 1.24-3.83, p = 0.002) to have the ability to pay user fees than those without. Two other significant indicators associated with mother's ability to pay user fees were employment and knowledge of existence of the user charges. Over 79% of mothers indicated willingness to pay user charge fees. Mothers with income were nearly three times more likely (OR = 2.77, 95% CI 1.36-5.78, p = 0.002) willing to pay user charge fees than those without income. Other indicators that showed significant association with willingness to pay user charge fees were employment, income and knowledge of user charges. Although small proportion of mothers were unable to meet the user charges, results in this study showed majority of mothers were able and willing to pay user charges if they had prior information to the charges and supported by some form of income. The results of the study suggests the typical support practised by the society where the spouse and relatives assist with health care especially with maternal health is encouraging. However, the scope of this study cannot be used to generalise the trend in PNG because the scenerio in the rural areas will vary from urban.", "The authors examine accessibility and the sustainability of quality health care in a rural setting under two alternative cost recovery methods, a fee-for-service method and a type of social financing (risk-sharing) strategy based on an annual tax+fee-for-service. Both methods were accompanied by similar interventions aimed at improving the quality of primary health services. Based on pilot tests of cost recovery in the non-hospital sector in Niger, the article presents results from baseline and final survey data, as well as from facility utilization, cost, and revenue data collected in two test districts and a control district. Cost recovery accompanied by quality improvements increases equity and access to health care and the type of cost recovery method used can make a difference. In Niger, higher access for women, children, and the poor resulted from the tax+fee method, than from the pure fee-for-service method. Moreover, revenue generation per capita under the tax+fee method was two times higher than under the fee-for-service method, suggesting that the prospects of sustainability were better under the social financing strategy. However, sustainability under cost recovery and improved quality depends as much on policy measures aimed at cost containment, particularly for drugs, as on specific cost recovery methods.", "To assess the effects of ending cost sharing on use of outpatient services and how this was perceived by health workers and members of a health unit management committee.\n From 10 districts across Uganda, 78 health facilities were selected. Attendance at these facilities was assessed for eight months before and 12 months after cost sharing ended. The data represented 1 966 522 outpatient visits. Perceptions about the impact of ending cost sharing were obtained from the 73 health workers and 78 members of the health unit management committee who were available.\n With the end of cost sharing, the mean monthly number of new visits increased by 17 928 (53.3%), but among children aged <5 years the increase was 3611 (27.3%). Mean monthly reattendances increased by 2838 (81.3%) among children aged <5 years and 1889 (24.3%) among all people. Attendances for immunizations, antenatal clinics, and family planning all increased, despite these services having always been free. Health workers reported a decline in morale, and many health unit management committees no longer met regularly.\n Use of all services increased - even those that had never before been subject to fees. The loss of some autonomy by the health facility and diminished community governance of health facilities may have long term negative effects.", "The combined effects of increasing demand for health services and declining real public resources have recently led many governments in the developing world to explore various health financing alternatives. Faced with a significant decline during the 1980s in its real per capita expenditures, the Kenya Ministry of Health (MOH) introduced a new cost sharing programme in December 1989. The programme was part of a comprehensive health financing strategy which also included social insurance, efficiency measures, and private sector development. Early implementation problems led to the suspension in September 1990 of the outpatient registration fee, the major revenue source at the time. In 1991, the Ministry initiated a programme of management improvement and gradual re-introduction of an outpatient fee, but this time as a treatment fee. The new programme was carried out in phases, beginning at the national and provincial levels and proceeding to the local level. The impact of these changes was assessed with national revenue collection reports, quality of care surveys in 6 purposively selected indicator districts, and time series analysis of monthly utilization in these same districts. In contrast to the significant fall in revenue experienced over the period of the initial programme, the later management improvements and fee adjustments resulted in steady increases in revenue. As a percentage of total non-staff expenditures, fiscal year 1993-1994 revenue is estimated to have been 37% at provincial general hospitals, 20% at smaller hospitals, and 21% at health centres. Roughly one third of total revenue is derived from national insurance claims. Quality of care measures, though in some respects improved with cost sharing, were in general somewhat mixed and inconsistent. The 1989 outpatient registration fee led to an average reduction in utilization of 27% at provincial hospitals, 45% at district hospitals, and 33% at health centres. In contrast, phased introduction of the outpatient treatment fee beginning in 1992, combined with somewhat broader exemptions, was associated with much smaller decreases in outpatient utilization. It is suggested that implementing user fees in phases by level of health facility is important to gain patient acceptance, to develop the requisite management systems, and to orient ministry staff to the new systems.", "To evaluate the impact of the increase in consultation fees on malaria incidence in children presenting in the outpatient clinic of a privately funded hospital, we measured the impact of two fee increases on the number of pediatric outpatients. A 74% reduction in outpatients and a 78% reduction in malaria cases occurred in a course of four years. No differences were observed in an adjacent public hospital that does not charge consultation fees. This surprisingly strong effect may be the basis for increase in malaria morbidity and mortality, since in the time course of 4 years, an estimated 3000 children did not receive adequate malaria treatment in this region. Furthermore, it may drive parasite resistance, due to inadequate auto-medication.", "Family planning program managers may be easily misled by conclusions about the effects of price increases on the demand for services when the findings are based on pre-experiments such as the single-group pretest-posttest study, generally believed to be practical. This report presents financial and service data from clinics of the Asociación Pro-Bienestar de la Familia Ecuatoriana (APROFE) in Ecuador, which, analyzed according to the single-group pretest-posttest design, would suggest that the demand for intrauterine device services is inelastic. However, considerable demand elasticity is detected when data are analyzed according to more rigorous quasi-experimental designs. Using the single-group pretest-posttest design for pricing studies is too flawed to be considered practical. Wherever possible, strong designs should be used in operations research, especially in pricing studies.", "To document the effects of the abolition of user fees on utilization of health services in Uganda with emphasis on poor and vulnerable groups.\n A longitudinal study using quantitative and qualitative methods was carried out in 106 health facilities across the country. Health records were reviewed to determine trends in overall utilization patterns and use among vulnerable groups. A modification of wealth ranking as defined by the Uganda Poverty Participatory Assessment Project was used to categorize households by socio-economic status in order to compare utilization by the poor against that of other socio-economic groups.\n There was a marked increase in utilization in all population groups that was fluctuating in nature. The increase in utilization varied from 26% in public referral facilities in 2001, rising to 55% in 2002 compared with 2000. The corresponding figures for the lower level facilities were 44% and 77%, respectively. Increase in utilization among the poor was more than for other socio-economic categories. Women utilized health services more than men both before and after cost-sharing. Higher increases in utilization were noted among the over-five age group compared with the under-fives. There were no increases in utilization for preventive and inpatient services. With respect to quality of care, there were fewer drug stock-outs in 2002 compared with 2000 and 2001. There was no deterioration of other indicators such as cleanliness, compound maintenance and staff availability reported.\n The study suggests that there is a financial barrier created by cost-sharing that decreases access to services, especially among the poor in Uganda. However, further studies are needed to clarify issues of utilization by age and gender.", "The Government of Kenya introduced user fees for inpatient and curative outpatient care at its hospitals and health centres in December 1989. Children under five years old and those judged by the health staff to be indigent were among the groups exempted from fees. In September 1990, outpatient registration fees were removed, but other fees were retained. This paper describes the effects of these policy changes on the use of health services in Kibwezi division, a poor rural area. It focuses particularly on the impact of the fees on access to care by children and the poor. The assessment is based on attendance data from government health facilities and on a longitudinal household survey of health care utilization, which covered the nine months during which all fees were charged and two months following the removal of the registration fees. Attendance at government fee-charging health facilities for both outpatient and inpatient care was lower during the period when full fees were charged than during the same months of the previous year. Outpatient attendances rose again when the registration fees were lifted. The study households reported lower levels of utilization of public hospitals and health centres when full fees were in force than during the period after the registration fees were lifted. The pattern of utilization by young children, who were exempted from fees, mirrored that of the rest of the population, suggesting that they were not fully protected from the adverse effects of fees. The poorest households made much less use of the fee-charging government facilities than the better-off households.(ABSTRACT TRUNCATED AT 250 WORDS)", "Since the Bamako Initiative was launched in 1988, many African countries have embarked on comprehensive primary health care programs relying, at least partially, on revenues generated through user fees to revitalize health care delivery systems. Although these programs contain two critical components, user fees and improved quality, policy debates have tended to focus on the former and disregarded the latter. The purpose of this study is to provide a net assessment of these two components by testing how user fees and improved quality affect health facility utilization among the overall population and specifically among the poorest people. A \"pretest-posttest controlled\" experiment was conducted in five public health facilities in the Adamaoua province of Cameroon. Three health centers which were to introduce a user fee and quality improvement (i.e. reliable drug supply) policy were selected as \"treatment\" centers and two comparable facilities not yet phased into this policy were selected as \"controls\". Two rounds of household surveys were conducted (each to 800 households in 25 villages surrounding the five study sites) to measure the percentage of ill people seeking care at the health center before and after the implementation of the policy. The experiment was tightly controlled by conducting monthly observations at each study site. Results indicate that the probability of using the health center increased significantly for people in the \"treatment\" areas compared to those in the \"control\" areas. Travel and time costs involved in seeking alternative sources of care are high; when good quality drugs became available at the local health center, the fee charged for care and treatment represented an effective reduction in the price of care and thus utilization rose. Moreover, contrary to previous studies which have found that the poorest quintile is most hurt by user fees, this study found that probability of the poorest quintile seeking care increases at a rate proportionately greater than the rest of the population. Since the poor are most responsive to price changes, they appear to be benefitting from local availability of drugs more than others.", "User fees are used to recover costs and discourage unnecessary attendance at primary care clinics in many developing countries. In South Africa, user fees for children aged under 6 years and pregnant women were removed in 1994, and in 1997 all user fees at all primary health care clinics were abolished. The intention of these policy changes was to improve access to health services for previously disadvantaged communities. We investigated the impact of these changes on clinic attendance patterns in Hlabisa health district. Average quarterly new registrations and total attendances for preventive services (antenatal care, immunization, growth monitoring) and curative services (treatment of ailments) at a mobile primary health care unit were studied from 1992 to 1998. Regression analysis was undertaken to assess whether trends were statistically significant. There was a sustained increase in new registrations (P = 0.0001) and total attendances (P = 0.0001) for curative services, and a fall in new registrations (P = 0.01) and total attendances for immunization and growth monitoring (P = 0.0002) over the study period. The upturn in demand for curative services started at the time of the first policy change. The decreases in antenatal registrations (P = 0.07) and attendances (P = 0.09) were not statistically significant. The number of new registrations for immunization and growth monitoring increased following the first policy change but declined thereafter. We found no evidence that the second policy change influenced underlying trends. The removal of user fees improved access to curative services but this may have happened at the expense of some preventive services. Governments should remain vigilant about the effects of new health policies in order to ensure that objectives are being met.", "Donor funding for family planning and reproductive health (FP/RH) has declined in Latin America over the past decade, obliging providers to consider other financing mechanisms, including cost recovery through user fees. Pricing decisions are often difficult for providers, who fear that increased fees will cripple demand and create barriers to access for poor clients. Providers need information on how changes in price can affect utilization of services, and how to resolve trade-offs between generating income and serving poor clients. This paper reports on an experiment that measured the impact of higher client fees on utilization, revenue and client socioeconomic characteristics at 15 clinics operated by CEMOPLAF, an Ecuadoran not-for-profit FP/RH agency. The study improves on previous research by comparing effects of different price levels on demand for services. We conclude that demand was inelastic for three of CEMOPLAF's four main FP/RH services, and we found no evidence that the price increases had a disproportionate impact on utilization by poorer clients. The study therefore provided CEMOPLAF managers with knowledge that price increases at the levels tested would help to achieve sustainability goals (by increasing locally generated income) without undermining CEMOPLAF's social mission.", "To gauge the effects of operating the Bamako Initiative in Kongoussi district, Burkina Faso.\n Qualitative and quasi-experimental quantitative methodologies were used.\n Following the introduction of fees-for-services in July 1997, the number of consultations for curative care fell over a period of three years by an average of 15.4% at \"case\" health centres but increased by 30.5% at \"control\" health centres. Moreover, although the operational results for essential drugs depots were not known, expenditure increased on average 2.7 times more than income and did not keep pace with the decline in the utilization of services. Persons in charge of the management committees had difficulties in releasing funds to ensure access to care for the poor.\n The introduction of fees-for-services had an adverse effect on service utilization. The study district is in a position to bear the financial cost of taking care of the poor and the community is able to identify such people. Incentives must be introduced by the state and be swiftly applied so that the communities agree to a more equitable system and thereby allow access to care for those excluded from services because they are unable to pay.", "We investigated the impact of a short-lived policy of charging fees to patients attending public-sector outpatient health facilities in Kenya by collecting data on attendance at Nairobi's Special Treatment Clinic for sexually transmitted diseases (STDs) before (23 months), during (9 months), and after (15 months) the user-charge period. During the user-charge period, the seasonally adjusted total mean monthly attendance of men decreased significantly to 40% (95% CI 36-45) of that before fees were levied. Attendance rose in the post-user-charge period, but reached only 64% (59-68) of the pre-user-charge level. For women, the adjusted total mean monthly attendance during the user-charge period was reduced significantly to 65% (55-77) of the pre-user-charge level. Mean monthly attendance by women rose in the post-user-charge period to 22% (9-37) above the pre-user-charge level. There was no evidence of an increase in attendance over the course of the user-charge period among either men or women. The introduction of user fees probably increased the number of untreated STDs in the population, with potentially serious long-term health implications. The user-fee experience in Kenya should be carefully evaluated before similar measures are introduced elsewhere." ]

[ "10441604", "14872039" ]

[ "Phenobarbital compared with phenytoin for the treatment of neonatal seizures.", "Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study." ]

[ "Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly.\n From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 microg per milliliter for phenobarbital and 3 microg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria.\n Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment.\n Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates.", "The authors conducted a randomized trial of second-line anticonvulsant treatments for neonates. The response to treatment was assessed using continuous video-EEG because the clinical diagnosis of seizure in neonates is known to be unreliable. Of 27 neonates with EEG-confirmed seizures, 5 were excluded because of protocol violations, and 11 responded to phenobarbitone in a dose of 40 mg/kg as first line. Three of five neonates treated with lignocaine responded. Six neonates were treated with benzodiazepines as second line: None responded, and their neurodevelopmental outcome was poor." ]

[ "8970221" ]

[ "Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial." ]

[ "Fungal septicemia is a devastating disease in the neonate, especially in the low birth weight preterm infant who is especially vulnerable to disseminated fungal sepsis. The objective of this study was to compare the efficacy, safety and overall convenience of fluconazole vs. amphotericin B for the treatment of disseminated fungal sepsis in neonates.\n A prospective, randomized, collaborative study conducted at two South African neonatal units.\n Twenty-four infants with proven fungal septicemia were treated from June, 1992, to June, 1993. Twelve received fluconazole, 11 received amphotericin B and 1 was excluded. Assessment of hepatic, renal and hematologic functions were performed before, during and after treatment. The two groups were comparable at the time of enrollment into the study.\n Infants receiving amphotericin B had significantly higher values of total and direct bilirubin and alkaline phosphatase values at the end of treatment, while the fluconazole group showed a significant increase in the platelet count. The cumulative total numbers of days receiving intravenous therapy for the administration of antifungal drugs were 57 for the fluconazole group and 162 for the amphotericin group; no central lines were needed in the fluconazole group, whereas 3 babies given amphotericin B had central catheters for a cumulative total of 27 days. The case fatality rate was 33% in the fluconazole group and 45% in the amphotericin B group; there was still proof of fungal septicemia at the time of death in 1 patient given amphotericin B and 2 given fluconazole.\n Fluconazole showed fewer side effects than amphotericin B and was more convenient to use." ]

[ "9434669", "16084925", "15603634", "15018343", "9708578" ]

[ "The impact of regular multidisciplinary team interventions on psychotropic prescribing in Swedish nursing homes.", "Can a facilitated programme promote effective multidisciplinary audit in secondary care teams? An exploratory trial.", "Benefits of multidisciplinary case conferencing using audiovisual compared with telephone communication: a randomized controlled trial.", "Effects of interdisciplinary rounds on length of stay in a telemetry unit.", "A firm trial of interdisciplinary rounds on the inpatient medical wards: an intervention designed using continuous quality improvement." ]

[ "To evaluate the impact of regular multidisciplinary team interventions on the quantity and quality of psychotropic drug prescribing in Swedish nursing homes.\n A randomized controlled trial.\n A sample of 33 nursing homes: 15 experimental homes and 18 control homes representing 5% of all Swedish nursing homes.\n The sample consisted of 1854 long-term care residents with an average age of 83 years. Seventy percent of the residents were women, and 42% had a documented diagnosis of dementia. An additional 5% had a psychotic disorder, and 7% had a diagnosis of depression.\n Experimental homes participated in an outreach program that was designed to influence drug use through improved teamwork among physicians, pharmacists, nurses, and nurses' assistants. Multidisciplinary team meetings were held on a regular basis throughout the 12-month study period.\n Lists of each resident's prescriptions were collected 1 month before and 1 month after the 12-month intervention. Measures included the proportion of residents with any psychotropic drug, polymedicine, and therapeutic duplication and proportion of residents with nonrecommended and acceptable drugs in each psychotropic drug class, as defined by current Swedish guidelines.\n Baseline results show extensive psychotropic drug prescribing, with the most commonly prescribed drugs being hypnotics (40%), anxiolytics (40%), and antipsychotics (38%). After 12 months of team meetings in the experimental homes, there was a significant decrease in the prescribing of psychotics (-19%), benzodiazepine hypnotics (-37%), and antidepressants (-59%). Orders for more acceptable antidepressants also increased in the experimental homes. In the control homes there was increased use of acceptable antidepressants, but there were no significant reductions in other drug classes.\n There is excessive prescription of psychotropic drugs in Swedish nursing homes. Improved teamwork among caregivers can improve prescribing as defined by clinical guidelines.", "This 24-month exploratory study evaluated whether a 6-month programme supported by a trained external facilitator was feasible, acceptable and led to the adoption of a multidisciplinary approach to audit by secondary care staff. Undertaken in five acute hospital sites in the East Midlands UK, 22 multidisciplinary teams were randomised to either an intervention or control arm. Employing mixed methods, a range of outcomes, including collaborative behaviour, was measured. The intervention was feasible and acceptable to staff. Involvement in the facilitated programme had a positive impact on self-reported knowledge (P=0.000 post-intervention and at 4-months follow-up), skills (P=0.000 post-intervention and P=0.02 at 4-months follow-up) and attitudes (P<0.01 post-intervention), appeared to have some influence on improving self-reported (P<0.05 post-intervention) and observed collaborative behaviour (P=0.01) and led to better quality audit resulting in measurable improvements to care. Improved collaborative behaviour may have resulted from an increase in assertive behaviour by nurses. Research to test approaches to support teams to work effectively together is currently hampered by a lack of suitable research instruments and needs addressing before main (phase 111) trials are undertaken.", "Multidisciplinary case conferencing using a video-link was compared with multidisciplinary case conferencing by telephone. One hundred patients were randomized to either videoconferencing (intervention group, 50 patients) or audioconferencing (control group, 50 patients). The effectiveness of the intervention compared with the control was evaluated in terms of: the number of conferences per patient, average length of conference, length of treatment, number of occasions of service, degree of multidisciplinary team involvement, recorded level of communication, quality of the management plan (in terms of the number of points contained in it) and staff satisfaction. The intervention and control groups showed significant differences on only two of the outcome measures: the mean number of case conferences per patient was less for the intervention group, and the intervention group had a shorter length of treatment (6 days) than the control group (10 days). The study did not demonstrate any significant differences in occasions of service or time commitment, which might have resulted in lower costs. However, the introduction of case conferencing by video-link was accompanied by a high level of satisfaction on the part of the 14 team members who were interviewed.", "Interdisciplinary rounds (IRs) have been proposed to improve staff communication and reduce LOS. There have been no studies of IRs on an inpatient telemetry ward. Patients on a telemetry unit of a community hospital were randomly assigned to either an IR intervention or standard care. Charts were reviewed to determine LOS, patient characteristics, and indirect indices of quality of care.\n Daily work rounds, in which resident physicians, nurses, and ancillary staff meet to discuss patients on the team.\n 84 patients were enrolled, 42 randomized to the intervention and 42 to standard care. There was no significant difference in LOS. Indirect measures of quality of care (dietician, pharmacist, or physical therapist visit) did not differ. In a multiple linear regression model, only abnormal laboratory data, the presence of dementia, and the presence of a home health aid significantly predicted LOS.\n IRs did not decrease LOS in a telemetry ward. Whereas a potential benefit of IRs in other settings cannot be ruled out, this study emphasizes the importance of rigorous testing of strategies to enhance the quality or reduce the costs of inpatient care.", "In August 1993 a group of house staff and nursing staff at MetroHealth Medical Center formed a quality improvement team to evaluate the process of medical care on the inpatient wards. Using standard continuous quality improvement (CQI) methods, a team of medical interns, nurses, and other health professionals involved in patient care on the medicine inpatient service designed interdisciplinary, daily work rounds to improve the care of patients on the inpatient wards.\n The authors conducted a randomized, controlled firm trial of the impact of interdisciplinary rounds on the inpatient medicine services. The trial lasted 6 months (November 1993-April 1994) and included 1,102 admissions randomly assigned to experimental or control teams by the pre-existing firm system. Of the 1,102 admissions included in the study, 535 were randomized to medical services with traditional rounds and 567 to medical services with interdisciplinary rounds. The outcomes studied included length of stay (LOS), total hospital charges, provider satisfaction, and ancillary service efficiency.\n Unadjusted analysis for log-transformed data showed lower length of stay and total charges for the interdisciplinary group. The mean LOS for interdisciplinary rounds was 5.46 days, compared with 6.06 days for traditional care (P = 0.006), whereas mean total charges were $6,681 and $8,090 (P = 0.002) for the two groups, respectively. After multivariate regression analysis using a propensity score that included gender, age, marital status, admission source, diagnosis-related group (DRG) weight, and primary diagnosis by International Classification of Diseases, Ninth Revision (ICD-9) cluster, these differences remained statistically significant.\n Previous studies of interdisciplinary teams have failed to show statistically significant cost savings. This study involving more patients shows both cost and LOS decreases with the use of interdisciplinary teams. At the end of the 6-month trial, interdisciplinary rounds were instituted on all medicine inpatient services." ]

[ "1951565", "15913621", "9332992", "4050895", "8765270", "19517694", "12706276", "1453405", "2758900", "10192481", "2008006", "3904456", "2193511", "2187344", "10023873" ]

[ "Prophylactic amnioinfusion as a treatment for oligohydramnios in laboring patients: a prospective, randomized trial.", "Therapeutic amnioinfusion for intrapartum fetal distress using a pediatric feeding tube.", "Lipid peroxidation in cord blood: a randomised sequential pairs study of prophylactic saline amnioinfusion for intrapartum oligohydramnios.", "Saline amnioinfusion for relief of repetitive variable decelerations: a prospective randomized study.", "Transabdominal amnioinfusion in oligohydramnios at term before induction of labor with intact membranes: a randomized clinical trial.", "Amnioinfusion for relief of recurrent severe and moderate variable decelerations in labor.", "Prophylactic transcervical amnioinfusion in laboring women with oligohydramnios.", "Prophylactic intrapartum amnioinfusion for patients with oligohydramnios. A prospective randomized study.", "[Intrapartum amnio-infusion in patients with oligohydramnios].", "Amnioinfusion in term labor with low amniotic fluid due to rupture of membranes: a new indication.", "A prospective, randomized evaluation of intrapartum amnioinfusion. Fetal acid-base status and cesarean delivery.", "Prophylactic intrapartum amnioinfusion in patients with preterm premature rupture of membranes.", "Prophylactic intrapartum amnioinfusion: a randomized clinical trial.", "A prospective randomized study of saline solution amnioinfusion.", "Intrapartum amnioinfusion in women with oligohydramniosis. A prospective randomized trial." ]

[ "Prophylactic amnioinfusion was studied in a randomized sample of 305 patients with oligohydramnios in labor. One hundred seventy-five patients underwent amnioinfusion with the remainder serving as controls. Amniotic fluid was titrated to an amniotic fluid index greater than 10.0 cm in the treatment group. Patients receiving amnioinfusion had significantly less operative intervention for fetal distress (p = 0.0001) and fewer cesarean sections (p = 0.0001). Umbilical artery pH at the time of delivery also was increased (p = 0.0001). Rates of amnionitis and endometritis were not significantly different between infused patients and controls, although the length of hospital stay was significantly decreased (p = 0.002) in the treatment group. Our data support earlier reports in the literature that amnioinfusion is a useful technique for decreasing intrapartum morbidity for both mother and fetus.", "To evaluate the role of therapeutic amnioinfusion using a pediatric feeding tube in cases of intrapartum fetal distress.\n A randomized clinical trial including 438 women admitted in labor at Assiut University Hospital with nonreassuring fetal heart rate tracing. Using sealed opaque envelopes, the women were randomized to 2 groups. In the amnioinfusion group they underwent transcervical amnioinfusion (1000 mL of warmed sterile saline solution) in addition to conventional treatment. In the control group they received conventional treatment only. The primary outcome was cesarean section rate for fetal distress. The secondary outcomes were neonatal and maternal complications.\n The amnioinfusion group showed a significant reduction in the rate of cesarean section for fetal distress (relative risk [RR], 0.7; 95% confidence interval [CI], 0.6-0.83), and a 30% reduction in abnormal fetal heart rate patterns (RR, 0.7; 95% CI, 0.6-0.83). Significantly fewer newborns had Apgar scores less than 7 at 1 and 5 min in the amnioinfusion group than in the control group (RR, 0.38; 95% CI, 0.26-0.55 and RR, 0.31; 95% CI, 0.15-0.64, respectively). Significantly fewer newborns had meconium below the vocal cords in the amnioinfusion group than in the control group (RR, 0.36; 95% CI, 0.13-0.97). Moreover, 14 newborns in the amnioinfusion group needed admission to the intensive care unit vs. 31 newborns in the control group. There were no significant differences between the 2 groups regarding the incidence rates of uterine hypertonus and maternal temperature higher than 38 degrees C.\n Therapeutic amnioinfusion is a simple and effective intervention that reduces the rates of cesarean section for intrapartum nonreassuring fetal heart tracing. In under-resourced settings, it can be performed using inexpensive catheters.", "To determine the efficacy of prophylactic intrapartum amnioinfusion in reducing cord arterial lipid peroxide levels in cases of intrapartum oligohydramnios.\n Sequential randomised pairs trial.\n Delivery suite of a teaching hospital, the Chinese University of Hong Kong.\n Women with singleton, term pregnancy, cephalic presentation, clear amniotic fluid and an amniotic fluid index < or = 5 cm, with a normal intrapartum fetal heart rate tracing within 30 minutes of amniotomy.\n Selected patients were randomised either for prophylactic saline amnioinfusion or as control cases. Cord arterial lipid peroxide concentrations and acid base balance were determined at delivery.\n Operative intervention for fetal distress, cord arterial malondialdehyde and organic hydroperoxide levels, pH and base excess.\n Amnioinfusion was associated with significant reductions in the incidence of operative delivery for fetal distress and in lipid peroxide levels, an increase in base excess, but no significant alteration in pH.\n Oligohydramnios in labour is associated with high levels of lipid peroxidation, reflecting cellular damage by release of free radicals following hypoxia reperfusion. Prophylactic intrapartum saline amnioinfusion is an effective technique for the reduction of lipid peroxidation and of the incidence of operative intervention for fetal distress but has no significant effect on overall operative delivery rates.", "A prospective randomized study was undertaken in order to further investigate the effect of intrauterine saline amnioinfusion for the relief of repetitive variable decelerations in the first stage of labor. Intrauterine saline amnioinfusion corrects the oligohydramnios that makes the cord more vulnerable to compression during uterine contractions. Included in this study were 96 patients who had repetitive variable decelerations not relieved either by changes in position or by oxygen. Randomization resulted in 49 patients in the infusion group and 47 patients in the noninfusion group. Relief of variable decelerations was 51% in the infusion group, as compared to 4.2% in the noninfusion group. Relief of variable decelerations was more dramatic in the nulliparous infusion group (66.7%) than in the noninfusion group (0%). In the nulliparous patients there was a significant decrease in the rate of cesarean sections for fetal distress, being 14.8% in the infusion group as compared to 47.6% in the noninfusion group. This study clearly showed that saline amnioinfusion is a logical, simple, safe, and effective therapy for the relief of repetitive variable decelerations in the first stage of labor and can lower the incidence of cesarean sections for fetal distress in nulliparous patients. Furthermore, amnioinfusion was much superior to changes in position in treating repetitive variable decelerations.", "Our purpose was to determine the effectiveness of transabdominal amnioinfusion before induction of labor in reducing the incidence of fetal distress in pregnancies with oligohydramnios at term.\n Between June 1991 and September 1994 primiparous women with ultrasonographic evidence of oligohydramnios at term, intact membranes, and unripe cervix (Bishop score < or = 6), candidates for induction of labor with cervical or vaginal prostaglandin E2 gel, were randomly selected to receive transabdominal amnioinfusion (amnioinfused group, n = 39) or to proceed with direct labor induction (control group, n = 40). Inclusion criteria were (1) singleton gestation, (2) vertex presentation, (3) ultrasonographic estimation of fetal weight > or = 2500 gm, and (4) reactive nonstress test. Fetoneonatal outcome variables were compared between the two groups. Statistical analysis used contingency tables, Student t test, or Wilcoxon rank-sum tests, where applicable.\n Amnioinfusion was successfully performed in 100% of the patients randomized for the procedure. The incidence of severely abnormal fetal heart rate tracings was significantly higher in the control than in the amnioinfused group (42% [17/33] vs 5% [2/37], relative risk 12.9, 95% confidence interval 2.4 to 56.4). The rate of cesarean sections performed for fetal distress was fivefold higher in the control group (25% [10/40] vs 5% [2/39], relative risk 4.9, 95% confidence interval 1.1 to 32.4). No bleeding complications or fetomaternal infectious morbidity were noticed.\n Transabdominal amnioinfusion is a safe, effective option for the prevention of fetal distress in pregnancies with oligohydramnios at term with intact membranes and unripe cervix.", "To determine whether intrapartum amnioinfusion (AI) relieves recurrent moderate and severe variable decelerations in laboring women with clear or grade I meconium-stained amniotic fluid and reduces cesarean section rate for fetal distress.\n A randomized controlled trial was conducted in labor unit of Christian Medical College Hospital, Vellore, India, between October 2003 and September 2004. Women were randomized to receive AI (group I) and not to receive it (group II).\n A total of 150 women (75 in each group) were included in the study. There was significant relief of variable decelerations in group I and no difference in overall cesarean section rate but significant reduction in cesarean section rate for fetal distress in group I, and significant reduction in cesarean section rate for fetal distress in nulliparous women of group I. Neonatal acidemia was also significantly reduced in the nulliparous women receiving AI. The duration of maternal postpartum hospital stay was significantly reduced in group I. There were no adverse maternal or neonatal outcomes.\n AI was a beneficial therapeutic intervention in women patients showing fetal distress in first stage of labor, and it reduced cesarean section for fetal distress and neonatal acidemia.", "Evaluation of prophylactic intrapartum amnioinfusion in women with oligohydramnios.\n Assiut University Hospital during the period from February 2000 to September 2001, 160 laboring women with oligohydramnios [amniotic fluid index (AFI) </=5 cm] were randomized into: amnioinfusion and control groups. Inclusion criteria were: term singleton gestation, vertex presentation, cervical dilatation <4 cm, and assuring fetal heart rate (FHR). Trans-cervical amnioinfusion was done with warmed normal saline.\n there was a significant increase in AFI after amnioinfusion (P<0.001). The amnioinfusion group showed lower cesarean section rate for fetal distress (P=0.003), lower incidence of abnormal FHR (P=0.006), fewer neonates with Apgar score <7 at 1 min (P<0.001), and 5 min (P=0.009), meconium below vocal cords (P<0.001), umbilical arterial pH<7.1 (P=0.003), and significantly shorter hospital stay (P=0.02).\n Prophylactic trans-cervical amnioinfusion is a simple, safe and effective procedure.", "This prospective study evaluated whether prophylactic saline amnioinfusion among patients with amniotic fluid index (AFI) < or = 5.0 cm decreases the incidence of adverse fetal outcomes. Randomization of 53 patients with decreased AFI at term, resulted in 21 patients' receiving prophylactic saline amnioinfusion early in labor, prior to development of an abnormal fetal heart rate tracing. For the treatment group the mean AFI on admission was 3.0 cm, and the postamnioinfusion AFI was 8.9 cm. For 32 comparison (noninfusion) patients, the mean AFI was 2.9 cm; the group consisted of 17 patients randomized to receive no amnioinfusion (control group) and 15 patients who refused to participate in the study. There was no statistically significant difference between the amnioinfused and nonamnioinfused patients with regard to age, parity, gestational age, AFI at admission or duration of first or second stage of labor. Amnioinfusion resulted in no statistically significant reduction in the incidence of recurrent variable decelerations/bradycardia (26.3% vs. 46.6%), intrapartum resuscitation with terbutaline (5.2% vs. 10.0%), cesarean section for fetal distress (9.5% vs. 9.3%), fetal-acidosis (10.5% vs. 12.0%) or Apgar scores < 7 at five minutes (5.2% vs. 0%) in patients with oligohydramnios.", "Patients with oligohydramnios are at increased risk of developing fetal distress during labor, presumably as the result of umbilical cord compression. Intrapartum saline amnio-infusion for short-term amnionic fluid replacement was performed in a prospective randomized manner in 60 cases of oligohydramnios during period of 1-year. Patients receiving amnio-infusion had significantly lower incidence of neonatal asphyxia and less cesarean sections as compared with the controls. No neonatal nor maternal complication occurred. The effect of amnio-infusion was also confirmed by B type ultrasonic examination. These results suggested that intrapartum saline amnio-infusion might be a hopeful therapy for patients with oligohydramnios.", "The null hypothesis was that the use of intrapartum amnioinfusion to induce term labor because of premature rupture of membranes when labor was complicated by low amniotic fluid volume due to vaginal loss would not improve fetal heart rate patterns, decrease the incidence of operative delivery, or improve neonatal acid-base status.\n 200 term pregnancies with low amniotic fluid due to vaginal loss were randomly chosen to receive intrapartum amnioinfusion or standard obstetric care without amnioinfusion. Fetal heart rate pattern, method of delivery and neonatal acid-base status were compared with Student's t test, chi-squared analysis, Mann-Whitney U- or Fisher's exact test.\n When amnioinfusion was used, the fetuses had lower rates of variable (74 vs. 91%, P<0.01) or late (26 vs. 58%, P<0.001) decelerations. Spontaneous deliveries were more frequent (77 vs. 59%, P<0.01) and cesarean sections less frequent (3 vs. 10%, P<0.05). Mean umbilical arterial (7.24+/-0.07 vs. 7.21+/-0.08, P<0.01) and venous (7.31+/-0.06 vs. 7.28+/-0.08, P<0.01) pH were significantly higher in newborns with amnioinfusion, and babies in this group had lower rates of neonatal acidemia of arterial (22 vs. 36%, P<0.005) or venous (13 vs. 26%, P<0.005) origin.\n Amnioinfusion improved fetal heart rate pattern, lowered the incidence of operative delivery, and improved neonatal acid-base status in term labor complicated by low amniotic fluid due to vaginal loss.", "Pregnancies with decreased amniotic fluid volume are prediposed to umbilical cord compression and variable fetal heart rate declerations. Intrapartum amnioinfusion has been utilized in an effort to reduce cord compression. Previous studies suggested that amnioinfusion may improve the fetal metabolic state and reduce the incidence of cesarean delivery in selected patients. In this study the hypothesis was tested that intrapartum amnioinfusion will relieve cord compression in pregnancies complicated by oligohydramnios and will result in a reduced incidence of fetal intolerance to labor as well as improved fetal acid-base status at delivery. Thirty-five patients fulfilling the inclusion criteria were randomized to either the control (n = 16) or amnioinfusion treatment group (n = 19). Analysis of the data suggested that the two groups were similar for the perinatal parameters evaluated. No differences were observed in the umbilical artery blood gas analysis or incidence of cesarean section between the two groups. Intrapartum amnioinfusion does not appear to improve the perinatal outcome in pregnancies with oligohydramnios.", "Patients with preterm premature rupture of the membranes are at increased risk to develop intrapartum variable decelerations and fetal distress. Short-term saline solution amnioinfusion may be of benefit in the treatment of variable or prolonged decelerations once they appear. In an effort to assess the benefit of prophylactic amnioinfusion, patients with preterm premature rupture of the membranes were studied during a 1-year period in a prospective randomized manner. Patients receiving prophylactic amnioinfusion had significantly decreased incidence and severity of variable decelerations in the first stage of labor (p less than 0.005). In the second stage of labor, the incidence of severe (p less than 0.005) and total (p less than 0.001) decelerations was also decreased in the treatment group. The umbilical arterial pH at delivery was significantly lower (p less than 0.001) as was the umbilical venous pH (p less than 0.005) in the newborn infants of control patients compared with those of patients receiving amnioinfusion. This suggests that prophylactic intrapartum amnioinfusion is of significant benefit in reducing the incidence of variable decelerations and improving the metabolic state in newborn infants born to women with preterm premature rupture of the membranes.", "Amnioinfusion was performed in a prospective, randomized trial of 60 women in the latent phase of labor with oligohydramnios, as defined by an amniotic fluid index less than or equal to 5.0 cm. All fetuses were at least 37 weeks' gestational age, had normal baseline fetal heart rate variability, and no clinically significant fetal heart rate decelerations at the outset. Subjects in the amnioinfusion group (n = 30) were titrated to and maintained at an amniotic fluid index level greater than or equal to 8.0 cm throughout labor. In the group receiving amnioinfusion, significantly lower rates of meconium passage (p = 0.04), severe variable decelerations (p = 0.04), end-stage bradycardia (p = 0.05), and operative delivery for fetal distress (p = 0.002) occurred. Significantly higher umbilical arterial blood pH values were also noted in the infusion group (p = 0.02). We conclude that prophylactic intrapartum amnioinfusion is an important technique for the reduction of intrapartum morbidity.", "We performed a prospective randomized study of saline solution amnioinfusion in four types of pregnancy complications: postterm pregnancy, variable decelerations in labor, preterm labor, and oligohydramnios-suspected growth retardation. A total of 100 patients were randomized, 43 to undergo amnioinfusion and 57 to be in a control group. Patients undergoing amnioinfusion had a significantly decreased incidence of postpartum endometritis (2.4% vs 19%, p = 0.01) and a lower incidence of cesarean delivery that was due to fetal distress in labor (4.7% vs 16%, p = 0.07). The use of amnioinfusion also made a significant contribution to the four-quadrant ultrasonographic estimate of amniotic fluid volume (14.7 vs 9.8 cm, p less than 0.001). All other maternal and neonatal outcome parameters were similar between the two groups. We conclude that saline solution amnioinfusion in labor may be a beneficial procedure but that further studies are needed.", "To evaluate the effects of amnioinfusion in oligohydramniosis.\n During a 20-month period, patients at term with oligohydramniosis (amniotic fluid index less than 5 cm) at Huddinge University and Norrköping Hospitals were recruited for a prospective randomized study to evaluate amnioinfusion. Informed consent was obtained from 112 patients who met the entry criteria. Sixty subjects were randomized to amnioinfusion and 52 to the control group. Outcome parameters included fetal heart rate abnormalities, mode of delivery, Apgar score, pH in umbilical artery blood and need for neonatal intensive care.\n The cesarean section rate was significantly reduced in the amnio-infusion group (29% versus 13%, p=0.043). No difference in time from randomization to delivery was detected between the two groups. The frequency of ominous fetal heart rate tracings with a cervical dilatation of 0-3 cm was the same in the two groups. The frequency of such heart rate patterns after amnioinfusion was significantly lower than in the control group. Neonatal outcome, pH in the umbilical artery blood and need for neonatal intensive care did not differ between the two groups.\n The present study confirms the findings of other authors that amnioinfusion effectively reduces the number of cesarean sections in cases of oligohydramniosis." ]

[ "9448611", "14526151", "16149365", "17650935", "12358242", "17164546", "11882400" ]

[ "Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial.", "A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II > or =6).", "2004 MacLean-Mueller prize enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment.", "[Total enteral nutrition vs. total parenteral nutrition in patients with severe acute pancreatitis].", "Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study.", "A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition.", "Early nasojejunal feeding in acute pancreatitis is associated with a lower complication rate." ]

[ "Parenteral nutrition is well established for providing nutritional support in acute pancreatitis while avoiding pancreatic stimulation. However, it is associated with complications and high cost. Benefits of enteral feeding in other disease states prompted a comparison of early enteral feeding with total parenteral nutrition in this clinical setting.\n Thirty-eight patients with acute severe pancreatitis were randomized into two groups. The first (n = 18) received enteral nutrition through a nasoenteric tube with a semi-elemental diet, while the second group (n = 20) received parenteral nutrition through a central venous catheter. Safety was assessed by clinical course of disease, laboratory findings and incidence of complications. Efficacy was determined by nitrogen balance. The cost of nutritional support was calculated.\n Enteral feeding was well tolerated without adverse effects on the course of the disease. Patients who received enteral feeding experienced fewer total complications (P < 0.05) and were at lower risk of developing septic complications (P < 0.01) than those receiving parenteral nutrition. The cost of nutritional support was three times higher in patients who received parenteral nutrition.\n This study suggests that early enteral nutrition should be used preferentially in patients with severe acute pancreatitis.", "Total enteral nutrition (TEN) within 48 h of admission has recently been shown to be safe and efficacious as part of the management of severe acute pancreatitis. Our aim was to ascertain the safety of immediate TEN in these patients and the effect of TEN on systemic inflammation, psychological state, oxidative stress, plasma glutamine levels and endotoxaemia.\n Patients admitted with predicted severe acute pancreatitis(APACHE II score >5) were randomised to total enteral (TEN; n = 8) or total parenteral nutrition (TPN; n = 9). Measurements of systemic inflammation (C-reactive protein), fatigue (visual analogue scale), oxidative stress (plasma thiobarbituric acid-reactive substances), plasma glutamine and anti-endotoxin IgG and IgM antibody concentrations were made on admission and repeated on days 3 and 7 thereafter. Clinical progress was monitored using APACHE II score. Organ failure and complications were recorded.\n All patients tolerated the feeding regime well with few nutrition-related complications. Fatigue improved in both groups but more rapidly in the TEN group. Oxidative stress was high on admission and rose by similar amounts in both groups. Plasma glutamine concentrations did not change significantly in either group. In the TPN group, 3 patients developed respiratory failure and 3 developed non-respiratory single organ failure. There were no such complications in the TEN group. Hospital stay was shorter in the TEN group [7(4-14) vs. 10 (7-26) days; p = 0.05] as was time to passing flatus and time to opening bowels [1 (0-2) vs. 2 (1-5)days; p = 0.01]. The cost of TEN was considerably less than of TPN.\n Immediate institution of nutritional support in the form of TEN is safe in predicted severe acute pancreatitis. It is as safe and as efficacious as TPN and may be beneficial in the clinical course of this disease.", "The optimal route of nutrition in severe pancreatitis is controversial. Parenteral nutrition (PN) is preferred, but enteral nutrition (EN) promises to attenuate inflammation and prevent sepsis. We hypothesized that EN was at least equivalent to PN in reducing inflammation, providing effective nutrition and being cost-effective.\n We conducted a randomized controlled trial comparing PN to EN in pancreatitis in an academic, multi-institutional, tertiary care health system. We screened 728 consecutive patients. Twenty-eight patients with a Ranson's score greater than 2 who did not tolerate clear fluids 4 days after admission were randomized: 18 to PN and 10 to EN. Both groups were provided daily 105 kJ (25 kcal)/kg and 1.5 g/kg of protein, respectively, until they could tolerate a regular diet.\n C-reactive protein in EN patients was reduced by 50% 5 days faster than PN patients (Wilcoxon test, p = 0.09). Both groups received a similar number of kilojoules and achieved near normal prealbumin and 24-hour urinary nitrogen values. Neither regimen caused a change in cholecystokinin levels. Overall mortality was 4.9% (3 patients in the PN group). In 5 patients (4 PN, 1 EN) there were infected pancreatic collections. Nine EN patients dislodged the nasojejunal tube. EN had an average cost of dollar 1375 per patient compared with dollar 2608 for PN (p = 0.08). After sensitivity analysis, EN cost dollar 957 compared with dollar 2608 for PN (p = 0.03).\n EN or PN is safe and provides adequate nutrition in severe pancreatitis. EN shows a trend toward faster attenuation of inflammation, with fewer septic complications and is the dominant therapy in terms of cost-effectiveness. This study favours EN for nutritional support in severe pancreatitis.", "To compare the efficacy of early total enteral nutrition (TEN) vs. total parenteral nutrition (TPN) in patients with severe acute pancreatitis (SAP).\n A total of 22 consecutive patients with SAP were randomized to receive TPN (group I) or TEN (group II). SAP was defined applying APACHE II score, C-reactive protein (CRP) measurements and/or Balthazar CT scan score. Acute inflammatory response (CRP, TNF-a, IL-6), visceral proteins (pre-albumin, albumin), complications (systemic inflammatory response syndrome, multiorgan failure, infections), surgical interventions, length of hospital stay and mortality were evaluated.\n No significant differences were found between the two groups in the APACHE II score, in CRP, TNF-a and IL-6 concentrations or in pre-albumin and albumin levels over the first 10 days. Seven patients in group I and 4 in group II suffered severe complications. Three patients in group I required surgical intervention. Length of hospital stay was alike in the two groups. Two patients from group I died in the course of the hospitalization.\n SAP patients with TEN feeding showed a tendency towards a better outcome than patients receiving TPN.", "The aims of this study were to define the indications for, and to evaluate the cost-effectiveness of, nutritional support in patients with acute pancreatitis.\n All admissions during the 12-month period from January through December 2000, were entered into a common management protocol consisting of an initial 48-h fast with i.v. fluids and analgesics. After 48 h, those patients who were improving were restarted on oral feeding (group O). The remaining patients were randomized to receive nasojejunal (group EN) or parenteral feeding (group TPN). The randomization study was continued until 50 patients had been accrued. Outcomes in the three groups were compared with respect to length of hospital stay, duration of feeding, complications, and hospital costs.\n A total of 156 admissions were evaluated in the first 12 months. Of these, 87% patients had mild disease, 10% moderate, and 3% severe; 62% were related to alcohol abuse, 18% gallstones, and 8% idiosyncratic drug reactions. Of the patients, 75% improved on 48 h bowel rest and i.v. fluids, and were discharged within 4 days. The remainder were randomized to jejunal elemental (n = 26) or parenteral (n = 27) feeding. Duration of feeding was shorter with EN (6.7 vs 10.8 days, p < 0.05) and nutrition costs were lower, representing an average cost saving of $2362.00 per patient fed. EN was less effective in meeting estimated nutritional requirements (54 vs 88%, p < 0.0001), but metabolic (p < 0.003) and septic complications (p = 0.01) were lower. Subgroup analysis of patients with severe disease showed similar findings.\n Despite concerns that metabolic expenditure is increased and that food-stimulated pancreatic secretion might exacerbate the disease process, hypocaloric enteral feeding seems to be safer and less expensive than parenteral feeding and bowel rest in patients with acute pancreatitis.", "Infectious complications are the main cause of late death in patients with acute pancreatitis. Routine prophylactic antibiotic use following a severe attack has been proposed but remains controversial. On the other hand, nutritional support has recently yielded promising clinical results. The aim of study was to compare enteral vs. parenteral feeding for prevention of infectious complications in patients with predicted severe acute pancreatitis.\n We screened 466 consecutive patients with acute pancreatitis. A total of 70 patients with objectively graded severe acute pancreatitis were randomly allocated to receive either total enteral nutrition (TEN) or total parenteral nutrition (TPN), within 72 h of onset of symptoms. Baseline characteristics were well matched in the two groups.\n The incidence of pancreatic infectious complications (infected pancreatic necrosis, pancreatic abscess) was significantly lower in the enterally fed group (7 vs. 16, p = 0.02). In the TEN group, 7 patients developed multiple organ failure whereas 17 parenterally fed patients developed multiple organ failure (p = 0.02). Overall mortality was 20% with two deaths in the TEN group and twelve in the TPN group (p < 0.01).\n Early TEN could be used as prophylactic therapy for infected pancreatic necrosis since it significantly decreased the incidence of pancreatic infectious complications as well as the frequency of multiple organ failure and mortality.\n Copyright 2006 S. Karger AG, Basel.", "We investigated the effect of early jejunal feeding on septic complications and mortality rate in patients with acute pancreatitis in a two-phase, prospective, controlled study.\n In the first, randomized phase of the study, conventional parenteral nutrition was compared with early (within 24-72 h after the onset of symptoms) enteral nutrition. Of 89 patients admitted with acute pancreatitis, 48 patients were randomized into a parenteral group (Rindex 10, Infusamin S, Intralipid 10%; 30 kcal/kg) and 41 patients into an enteral group (jejunal tube feeding; Survimed OPD; 30 kcal/kg).\n The rate of septic complications (infected pancreatic necrosis, abscess) was lower in the enteral group (P = 0.08, chi(2) test). In the second phase of the study, early jejunal feeding was combined with prophylactic imipenem (Tienam, 500 mg intravenously twice each day) when necrosis of the pancreas was detected by abdominal computed tomography. When the outcomes of 92 patients in the third group were compared with those of patients in the parenteral group, the rate of septic complications decreased significantly (P = 0.03). Multiple organ failure (P = 0.14) and mortality (P = 0.13) tended to decrease.\n We believe that the combination of early enteral nutrition and selective, adequate antibiotic prophylaxis may prevent multiple organ failure in patients with acute pancreatitis." ]

[ "15848990", "16697231", "17045832", "8821521" ]

[ "A double-blind treatment study of bacterial vaginosis with normal vaginal lactobacilli after an open treatment with vaginal clindamycin ovules.", "Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial.", "Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis.", "Therapy of bacterial vaginosis using exogenously-applied Lactobacilli acidophili and a low dose of estriol: a placebo-controlled multicentric clinical trial." ]

[ "The expected 4-week cure rate after conventional treatment of bacterial vaginosis are only 65-70%. In an attempt to improve the cure rate by adding probiotic lactobacilli we performed a double-blind placebo-controlled study of adjuvant lactobacilli treatment after an open treatment with vaginal clindamycin ovules. Women with bacterial vaginosis as defined by Amsel's criteria were treated with clindamycin ovules. Vaginal smears were collected and analysed according to Nugent's criteria. During the following menstruation period the women used, as an adjuvant treatment, either lactobacilli-prepared tampons or placebo tampons. The lactobacilli tampons were loaded with a mixture of freeze-dried L. fermentum, L. casei var. rhamnosus and L. gasseri. The cure rate was recorded after the second menstruation period. There was no improvement in the cure rate after treatment with lactobacilli-containing tampons compared to placebo tampons; the cure rates as defined by Amsel's criteria were 56% and 62%, respectively, and 55% and 63%, as defined by Nugent's criteria. This is the first study to report cure rates for women with 'intermediate' wet smear ratings according to Nugent's classification and this group had an overall cure rate of 44%. The cure rate of treatment of bacterial vaginosis was not improved by using lactobacilli-prepared tampons for one menstruation.", "This study enrolled 125 premenopausal women diagnosed with bacterial vaginosis (BV) by presence of vaginal irritation, discharge and 'fishy' odor, and Nugent criteria and detection of sialidase enzyme. The subjects were treated with oral metronidazole (500 mg) twice daily from days 1 to 7, and randomized to receive oral Lactobacillus rhamnosus GR-1 (1 x 10(9)) and Lactobacillus reuteri RC-14 (1 x 10(9)) or placebo twice daily from days 1 to 30. Primary outcome was cure of BV as determined by normal Nugent score, negative sialidase test and no symptoms or signs of BV at day 30. A total of 106 subjects returned for 30-day follow-up, of which 88% were cured in the antibiotic/probiotic group compared to 40% in the antibiotic/placebo group (p<0.001). Of the remaining subjects, 30% subjects in the placebo group and none in the probiotic group had BV, while 30% in the placebo and 12% in the probiotic group fell into the intermediate category based upon Nugent score, sialidase result and clinical findings. High counts of Lactobacillus sp. (>10(5) CFU/ml) were recovered from the vagina of 96% probiotic-treated subjects compared to 53% controls at day 30. In summary, this study showed efficacious use of lactobacilli and antibiotic in the eradication of BV in black African women.", "Bacterial vaginosis (BV) is particularly common in black women, and in Nigeria it is often caused by Mycoplasma, as well as Atopobium, Prevotella and Gardnerella sp. Antimicrobial metronidazole oral therapy is poorly effective in eradicating the condition and restoring the Lactobacillus microbiota in the vagina. In this study, 40 women diagnosed with BV by discharge, fishy odor, sialidase positive test and Nugent Gram stain scoring, were randomized to receive either two dried capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each night for 5 days, or 0.75% metronidazole gel, applied vaginally twice a day (in the morning and evening). Follow-up at day 6, 15 and 30 showed cure of BV in significantly more probiotic treated subjects (16, 17 and 18/20, respectively) compared to metronidazole treatment (9, 9 and 11/20: P=0.016 at day 6, P=0.002 at day 15 and P=0.056 at day 30). This is the first report of an effective (90%) cure of BV using probiotic lactobacilli. Given the correlation between BV and HIV, and the high risk of the latter in Nigeria, intravaginal use of lactobacilli could provide women with a self-use therapy, similar to over-the-counter anti-yeast medication, for treatment of urogenital infections.", "The efficacy of vaginal tablets (Gynoflor) containing 50 mg of a lyophilisate of viable, H2O2-producing Lactobacillus acidophilus (at least 10(7) colony forming units/tablet) and 0.03 mg estriol (CAS 50-27-1) for the treatment of bacterial vaginosis (BV) was tested in a multicentric, randomised, placebo-controlled clinical trial with parallel-group design. 32 non-menopausal women with positive diagnoses for BV, including intermediate cases, participated in the trial. Patients were diagnosed using the classical clinical parameters of BV according to Amsel and using microscopic analysis of the Gram-stained vaginal smear. A positive clinical diagnosis of BV required at least 2 of the following 4 clinical criteria to be positive; greyish-white, homogeneous leukorrhea; vaginal pH > 4.5; KOH test for volatile amines; presence of clue cells. Microscopic diagnosis of BV, on the other hand, was obtained if examination of the Gram-stained vaginal smear showed less than 6 lactobacilli per field of view (1000 x magnification). This corresponds to another definition of BV as \"lactobacilli deficiency syndrome\". The efficacy of the 6-day therapy with 1-2 vaginal tablets daily was evaluated using both clinical and microscopic analysis. Using Amsel's classical clinical parameters of BV, the cure rate (defined as < or = 1 of the 4 clinical criteria positive) two weeks after the start of therapy was 77% in the verum group and 25% in the placebo group. Four weeks after the start of therapy, the cure rate was 88% in the verum group and 22% in the placebo group. At both control examinations, the cure rate for the test group was significantly higher than that for the placebo group (p < 0.05, Fisher's exact test, 2-sided, significance level 0.05). In addition, the trial showed that after 6 days of treatment with the test preparation, the lactobacilli were capable of recolonising the vagina. A significant increase in the number of lactobacilli was observed in the Gram-stained vaginal smear for the patient group treated with the test preparation compared to the placebo patient group (p < 0.05, Fisher's exact test, 2-sided, significance level 0.05), two and four weeks after the start of the 6-day treatment." ]

[ "10342710", "12428233", "8849355", "15529389", "15452837", "16373258", "12124866" ]

[ "A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus.", "Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial.", "Dehydroepiandrosterone in systemic lupus erythematosus. Results of a double-blind, placebo-controlled, randomized clinical trial.", "The effect of dehydroepiandrosterone on lumbar spine bone mineral density in patients with quiescent systemic lupus erythematosus.", "Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus.", "Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus.", "Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial." ]

[ "To determine if dehydroepiandrosterone (DHEA) is beneficial in severe systemic lupus erythematosus (SLE).\n A double-blinded, placebo-controlled, randomized clinical trial in 21 patients with severe and active SLE, manifestated primarily by nephritis, serositis or hematological abnormalities. In addition to conventional treatment with corticosteroids +/- immunosuppressives, patients received DHEA 200 mg/d vs. placebo for 6 months, followed by a 6-month open label period. The primary outcome was a prospectively defined responder analysis, based on a quantitatively specified improvement of the principal severe lupus manifestation at 6 months.\n Nineteen patients were available for evaluation at 6 months. Baseline imbalance between the groups was noted, with the DHEA group having greater disease activity at baseline (P<0.05 by physician's global assessment). Eleven patients were responders: 7/9 patients on DHEA vs. 4/10 patients on placebo (P<0.10). Of the secondary outcomes, mean improvement in SLE disease activity index (SLE-DAI) score was greater in the DHEA group (-10.3+/-3.1 vs. -3.9+/-1.4. P<0.07). Bone mineral density at the lumbo-sacral spine showed significant reduction in the placebo group, but was maintained in the DHEA group.\n DHEA therapy, when added to conventional treatment for severe SLE, may at most have a small added benefit with respect to lupus outcomes, but baseline imbalances in the study population limit the generalizability of the results. DHEA appears to have a protective effect with respect to corticosteroid-induced osteopenia in such patients.", "To evaluate the efficacy and tolerability of dehydroepiandrosterone (DHEA) at a dosage of 200 mg/day in adult women with active systemic lupus erythematosus (SLE).\n In a multicenter randomized, double-blind, placebo-controlled trial, 120 adult women with active SLE received oral DHEA (200 mg/day; n = 61) or placebo (n = 59) for 24 weeks. The primary end point was the mean change from baseline in the Systemic Lupus Activity Measure (SLAM) score at 24 weeks of therapy. Secondary end points included time to first flare, change in SLE Disease Activity Index (SLEDAI) score, and physician's and patient's global assessment scores at week 24.\n The two groups were well balanced for baseline characteristics. Mean reductions in SLAM scores from baseline were similar and were not statistically significantly different between treatment groups (DHEA -2.6 +/- 3.4 versus placebo -2.0 +/- 3.8, mean +/- SD). The number of patients with flares was decreased by 16% in the DHEA group (18.3% of DHEA-treated patients versus 33.9% of placebo-treated patients; P = 0.044, based on time to first flare). The mean change in the patient's global assessment was statistically significant between the two groups (DHEA -5.5 versus placebo 5.4; P = 0.005). The number of patients with serious adverse events, most of which were related to SLE flare, was significantly lower in DHEA-treated patients compared with placebo-treated patients (P = 0.010). Expected hormonal effects, including increased testosterone levels and increased incidence of acne, were observed. No life-threatening reactions or serious safety issues were identified during this study.\n The overall results confirm that DHEA treatment was well-tolerated, significantly reduced the number of SLE flares, and improved patient's global assessment of disease activity.", "To determine if dehydroepiandrosterone (DHEA) is beneficial in the treatment of systemic lupus erythematosus (SLE).\n In a double-blind, placebo-controlled, randomized trial, 28 female patients with mild to moderate SLE were given DHEA 200 mg/day or placebo for 3 months. Outcomes included the SLE Disease Activity Index (SLEDAI) score, patient's and physician's overall assessments of disease activity, and concurrent corticosteroid dosages (which were adjusted as clinically indicated).\n In the patients who were receiving DHEA, the SLEDAI score, patient's and physician's overall assessment of disease activity, and concurrent prednisone dosage decreased, while in the patients taking placebo, small increases were seen. The difference in patient's assessment between the groups was statistically significant (P = 0.022, adjusted). Lupus flares occurred more frequently in the placebo group (P = 0.053). Mild acne was a frequent side effect of DHEA.\n DHEA may be useful as a therapeutic agent for the treatment of mild to moderate SLE. Further studies of DHEA in the treatment of SLE are warranted.", "Because dehydroepiandrosterone (DHEA) is an adrenal steroid hormone with weak intrinsic androgenic properties that can be converted in peripheral tissues into more potent sex hormones, one might expect a positive effect of DHEA on bone mineral density (BMD). We evaluated the effects on lumbar BMD of oral DHEA, 200 mg/day, for 1 year in female patients with quiescent systemic lupus erythematosus (SLE).\n The study subjects were 60 women with SLE. All participants gave informed consent to participate in a double-blind, placebo-controlled study on the effects of DHEA on fatigue and general well-being. BMD was measured with dual-energy x-ray absorptiometry (DEXA) at baseline and after 12 months.\n Fifty-eight patients (mean age 42.6 years) could be evaluated; 2 patients (both in the DHEA group) refused to undergo DEXA a second time. In premenopausal women, DHEA did not influence BMD significantly. There was a significant increase in BMD with use of DHEA in postmenopausal women who were not receiving bisphosphonates or estrogen-containing medications. This increase was not observed in the group receiving placebo.\n In premenopausal women with quiescent SLE, use of DHEA does not have a significant effect on BMD. DHEA may increase BMD in postmenopausal SLE patients if they are not already protected from bone loss by use of estrogens or bisphosphonates. Small numbers, due to the absence of stratification for menopausal status, and the use of antiresorptive agents at randomization preclude firmer conclusions based on the results of this study.", "To determine whether prasterone administration results in improvement or stabilization of systemic lupus erythematosus (SLE) disease activity and its symptoms.\n Women with active SLE were treated with prasterone 200 mg/day plus standard SLE treatments or with placebo plus standard SLE treatments for up to 12 months in this randomized, double-blind investigation conducted at 27 centers. Standard SLE treatments included prednisone (</=10 mg/day), antimalarials, and immunosuppressive agents; dosages were required to be stable for >/=6 weeks prior to enrollment and remain unchanged during protocol treatment. Responders were patients who experienced no clinical deterioration and had improvement or stabilization over the duration of the study in 2 disease activity measures (the SLE Disease Activity Index [SLEDAI] and the Systemic Lupus Activity Measure) and 2 quality of life measures (patient's global assessment and the Krupp Fatigue Severity Scale).\n A total of 381 women with SLE were enrolled. Among patients with clinically active disease at baseline (SLEDAI score >2), 86 of 147 in the prasterone group (58.5%) demonstrated improvement or stabilization without clinical deterioration, as compared with 65 of 146 in the placebo group (44.5%) (P = 0.017). Acne and hirsutism were reported in 33% and 16%, respectively, of the prasterone group and in 14% and 2%, respectively, of the placebo group (P < 0.05 for both comparisons). However, most cases of acne and hirsutism were mild and did not require withdrawal from therapy. Myalgias and oral stomatitis were reported less frequently in the prasterone group (22% and 15%, respectively) than in the placebo group (36% and 23%, respectively) (P < 0.05 for both comparisons). Serum levels of high-density lipoprotein cholesterol, triglycerides, and C3 complement significantly decreased, while levels of testosterone and, to a lesser extent, estradiol increased in the prasterone group.\n In adult women with active SLE, administration of prasterone at a dosage of 200 mg/day improved or stabilized signs and symptoms of disease and was generally well tolerated.", "The objective of this study was to evaluate the efficacy of low dose dehydroepiandrosterone (DHEA) on health-related quality of life (HRQOL) in glucocorticoid treated female patients with systemic lupus erythematosus (SLE). Forty one women ( >or= 5 mg prednisolone/day) were included in a double-blind, randomized, placebo-controlled study for 6 months where DHEA was given at 30 mg/20 mg ( <or= 45/ >or= 46 years) daily, or placebo, followed by 6 months open DHEA treatment to all patients. HRQOL was assessed at baseline, 6 and 12 months, using four validated questionnaires and the patients' partners completed a questionnaire assessing mood and behaviour at 6 months. DHEA treatment increased serum levels of sulphated DHEA from subnormal to normal. The DHEA group improved in SF-36 \"role emotional\" and HSCL-56 total score (both p<0.05). During open DHEA treatment, the former placebo group improved in SF-36 \"mental health\" (p<0.05) with a tendency for improvement in HSCL-56 total score (p=0.10). Both groups improved in McCoy's Sex Scale during active treatment (p<0.05). DHEA replacement decreased high-density lipoprotein (HDL) cholesterol and increased insulin-like growth factor I (IGF-I) and haematocrit. There were no effects on bone density or disease activity and no serious adverse events. Side effects were mild. We conclude that low dose DHEA treatment improves HRQOL with regard to mental well-being and sexuality and can be offered to women with SLE where mental distress and/or impaired sexuality constitutes a problem.", "To evaluate whether treatment with prasterone (dehydroepiandrosterone [DHEA]) would allow the dosage of prednisone (or an equivalent corticosteroid) to be reduced to < or = 7.5 mg/day for 2 months or longer while maintaining stable or reduced disease activity in steroid-dependent women with systemic lupus erythematosus (SLE).\n In a double-blind, randomized trial, 191 female SLE patients receiving prednisone (10-30 mg/day) were treated daily with either placebo, 100 mg of oral prasterone (an adrenal androgen), or 200 mg of oral prasterone for 7-9-months. At monthly intervals, corticosteroid dosages were reduced by algorithm in patients whose SLE Disease Activity Index (SLEDAI) score was stable or improved. Patients for whom a sustained reduction in the dosage of prednisone (< or = 7.5 mg/day) was achieved for at least the last 2 months of the 7-9-month treatment period were classified as responders.\n Response rates were 41% in the placebo group, 44% in the 100-mg prasterone group, and 55% in the 200-mg group (P = 0.110, 200 mg versus placebo). Among the 137 subjects (45 in the placebo group, 47 in the 100-mg group, and 45 in the 200-mg group) who had active disease at baseline (defined as SLEDAI score >2), 29%, 38%, and 51%, respectively, were responders (P = 0.031 for 200 mg prasterone versus placebo). Acne was the most common adverse event but was generally mild. Clinical and laboratory changes primarily reflected androgenic effects of prasterone.\n Among women with lupus disease activity, reducing the dosage of prednisone to < or = 7.5 mg/day for a sustained period of time while maintaining stabilization or a reduction of disease activity was possible in a significantly greater proportion of patients treated with oral prasterone, 200 mg once daily, compared with patients treated with placebo." ]

[ "15321573", "12566183", "15177859" ]

[ "Upright versus recumbent position in the second stage of labour in women with combined spinal-epidural analgesia.", "Ambulatory epidural anesthesia and the duration of labor.", "A prospective randomised trial on the effect of position in the passive second stage of labour on birth outcome in nulliparous women using epidural analgesia." ]

[ "Neuraxial blockade is widely used for pain relief in labour. This form of analgesia may be associated with an increase in instrumental delivery rates due to dystocia. 'Traditional' epidurals cause motor blockade and hence immobility. Using a low dose anaesthetic-opioid combination with either epidural or combined spinal-epidural, selective sensory blockade can be achieved, allowing mobility as well as pain relief. In this study, we randomised women with combined spinal-epidural analgesia either to mobilise (upright group n = 25) or to remain recumbent (n = 41) in the second stage of labour. We found women in the upright group had significantly shorter total second stage, (132 vs 109 min,P = 0.019) particularly during the pushing phase (73 vs 51 min, P = 0.011). Although there were fewer instrumental deliveries in the upright group, this was not statistically significant. Women who were randomised to the upright group, did actually mobilise. We conclude that mobilisation in the second stage of labour is possible, and may reduce the length of the second stage.", "Ambulatory epidural analgesia has become a common option for women in labor in France. We tested the hypothesis that a method of epidural analgesia that allowed women to walk had specific advantages regarding mode of delivery, consumption of local anesthetic, oxytocin requirement, and labor duration.\n Two hundred and twenty-one women with uncomplicated pregnancies who presented in spontaneous labor between 36 and 42 weeks of gestation or who were scheduled for induced labor were randomly divided into two groups, ambulatory and non-ambulatory. All were given intermittent epidural injections of 0.1% ropivacaine with 0.6 microg/ml sufentanil for analgesia during labor (P<0.05 was considered significant). None of the women had previous cesarean delivery.\n There were no significant differences between the two groups in mode of delivery, consumption of local anesthetic, or oxytocin requirement. However, a significant difference was noted in labor duration (173.4+/-109.9 min vs. 236.4+/-130.6 min; P=0.001).\n Walking with ambulatory labor analgesia shortens labor duration but has no other effect on the progress and outcome of labor.", "To determine whether the rate of instrumental birth in nulliparous women using epidural analgesia is affected by maternal position in the passive second stage of labour.\n A pragmatic prospective randomised trial.\n Consultant maternity unit in the Midlands.\n One hundred and seven nulliparous women using epidural analgesia and reaching the second stage of labour with no contraindications to spontaneous birth.\n The lateral versus the supported sitting position during the passive second stage of labour.\n Mode of birth, incidence of episiotomy, and perineal suturing.\n Recruitment was lower than anticipated (107 vs. 220 planned). Lateral position was associated with lower rates of instrumental birth rate (lateral group 33%; sitting group 52%; p=0.05, RR 0.64, CI for RR: 0.40-1.01; Number-needed-to-treat (NNT)=5), of episiotomy (45% vs. 64%; p=0.05, RR 0.66, CI for RR: 0.44-1.00, NNT=5), and of perineal suturing (78% vs. 86%; p=0.243, RR 0.75, CI for RR 0.47-1.17). The odds ratio for instrumental birth in the sitting group was 2.2 (CI 1.00-4.6). Logistic regression of potential confounder variables was undertaken, due to a large variation in maternal weight between the randomised groups. Of the nine possible confounders tested, only position of the baby's head at full dilation affected the risk of instrumental birth significantly (p=0.4, OR 2.7 where the fetal head was in the lateral or posterior position). Maternal weight did not appear to have any effect. The odds ratio for instrumental delivery for women randomised to the sitting position was slightly higher within the logistic regression model (adjusted OR 2.3).\n Women randomised to the lateral position had a better chance of a spontaneous vaginal birth than those randomised to the supported sitting position. Position of the babies head at full dilation had an additional effect on mode of birth. These effects are not conclusively generalizable. RECOMMENDATIONS FOR PRACTICE: The lateral position is likely to be at best beneficial, and at the worst no less harmful than the sitting position for most women and their babies who meet the criteria set for this study. Conclusive evidence for or against the technique should be established using larger trials." ]

[ "1880885", "8620707", "10759446", "12953145", "7743622", "9112877", "9052565" ]

[ "Group- vs home-based exercise training in healthy older men and women. A community-based clinical trial.", "A comparison between an outpatient hospital-based pulmonary rehabilitation program and a home-care pulmonary rehabilitation program in patients with COPD. A follow-up of 18 months.", "Comparison of effects of supervised versus self-monitored training programmes in patients with chronic obstructive pulmonary disease.", "Long-term effects of a maintenance program after supervised or self-monitored training programs in patients with COPD.", "Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years.", "Hospital vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease.", "Value of a supervised exercise program for the therapy of arterial claudication." ]

[ "--To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy, sedentary older adults.\n --Year-long randomized, controlled trial comparing (1) higher-intensity group-based exercise training; (2) higher-intensity home-based exercise training; (3) lower-intensity home-based exercise training; or (4) assessment-only control.\n --General community located in northern California.\n --One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease. One out of nine persons contacted through a community random-digit-dial telephone survey and citywide promotion were randomized.\n --For higher-intensity exercise training, three 40-minute endurance training sessions per week were prescribed at 73% to 88% of peak treadmill heart rate. For lower-intensity exercise training, five 30-minute endurance training sessions per week were prescribed at 60% to 73% of peak treadmill heart rate.\n --Treadmill exercise test performance, exercise participation rates, and heart disease risk factors.\n --Compared with controls, subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months (P less than .03). Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training. Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition (P less than .0005). There were no significant training-induced changes in lipid levels, weight, or blood pressure.\n --We conclude that (1) this community-based exercise training program improved fitness but not heart disease risk factors among sedentary, healthy older adults; (2) home-based exercise was as effective as group exercise in producing these changes; (3) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting; and (4) the exercise programs were relatively safe.", "In this study, the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program (HRP) are compared with those of a 12-week home-care rehabilitation program (HCRP) in COPD patients. A control group received no rehabilitation therapy.\n After randomization and stratification, effects on lung function, exercise performance (4-min walking test and cycle ergometer test), dyspnea, and leg effort during exercise, and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation (mean [SD] FEV1 percent predicted, 42.8 [8.4]).\n After HRP and HCRP, at 3 to 6 months after the start of the study, equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test. However, whereas after HRP at longer term values tended to return to baseline outcome, after HCRP a further ongoing significant improvement in exercise capacity was observed, while Borg dyspnea scores remained significantly improved over 18 months. Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP. Lung function, arterial oxygen saturation, and heart frequency during exercise did not change. A significant improvement in well-being was maintained over 18 months in both rehabilitation groups.\n Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation. Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting.", "The effects of two 8 week programmes of reconditioning in chronic obstructive pulmonary disease (COPD) patients were studied. Forty one subjects (mean+/-SD) 644.5) yrs; forced expiratory volume in one second (FEV1) 1.09+/-0.16 L; 40.6+/-6.2% predicted were randomly assigned either to supervised training on a treadmill, 4 days x week(-1) (group S; n=21) or walking 3 or 4 km in 1 h 4 days x week(-1), self-monitored with a pedometer, with weekly visits to encourage adherence (group SM; n=20). Patients were evaluated with the chronic respiratory diseases questionnaire (CRQ) and two exercise tests on a treadmill: incremental (IT) and constant (CT), above lactic threshold or 70% of maximal oxygen uptake (VO2, max) with arterial blood lactate determinations. Estimated mean work rate of training was 69+/-27 W and 25+/-5 W respectively for groups S and SM. Both types of training produced similar changes in the four dimensions of the CRQ. In group S reconditioning yielded significant (p<0.05) increases in VO2, max and increases in duration, with decreased lactate accumulation, ventilation, CO2 output (VCO2), heart rate (HR) and diastolic blood pressure (DBP) at the end of CT. They also adopted a deeper slower pattern of breathing during exercise. The SM group showed significant (p<0.05) increases in duration, lower HR and DBP at the end of CT. Significantly (p<0.05) different effects between S and SM programmes were changes in VO2, max 100+/-101 mL x min(-1) versus 5+/-101 mL x min(-1)), duration of the CT (8.1+/-4.4 min versus 3.9+/-4.7 min), VCO2 (-94+/-153 mL x min(-1) versus 48+/-252 mL x min(-1)), lactate accumulation (-1.3+/-2.2 mmol x L(-1) versus 0+/-1.2 mmol x L(-1) and respiratory rate at the end of CT (4.3+/-3.4 min(-1) versus -1+/-4.2 min(-1)). Supervised, intense training yields physiological improvements in severe chronic obstructive pulmonary disease patients not induced by self-monitored training. The self-monitored, less intense training, increases submaximal exercise endurance, although to a lesser degree.", "The evaluation of a 13-month maintenance program (MP) for 39 severe COPD patients with FEV(1)%pred 44(7)% who, as result of two different 8-week leg exercise training (LET) programs, one supervised at the hospital (group S; n = 20) and the other self-monitored (SM; n = 19), had achieved different levels of exercise tolerance. After LET, patients in group S had a higher maximal oxygen uptake and endurance time than patients in the SM group [ O(2)max 1.43(0.30) l. min(-1)] vs l.25(0.27) l. min(-1) and endurance-time 16(4) min vs 12 (5) min, respectively). During the MP patients were advised to walk vigorously at least 4 km/day, 4 times/wk. After the MP, while endurance time remained higher than at baseline, it had decreased ( p < 0.01) immediately after LET in both groups and no differences were evident between groups (11(4) min and 10(4), respectively). In contrast, Chronic Respiratory Diseases Questionnaire scores, which had improved significantly after LET in both groups, remained high. Long-term effects of MP were independent of the training strategy or whether physiological improvements had been obtained with the initial LET. SM exercise programs do not seem capable of maintaining physiological improvements in exercise tolerance, though \"quality of life\" can be maintained.", "Although exercise parameters such as intensity and format have been shown to influence exercise participation rates and physiological outcomes in the short term, few data are available evaluating their longer-term effects. The study objective was to determine the 2-year effects of differing intensities and formats of endurance exercise on exercise participation rates, fitness, and plasma HDL cholesterol levels among healthy older adults.\n Higher-intensity, group-based exercise training; higher-intensity, home-based exercise; and lower-intensity, home-based exercise were compared in a 2-year randomized trial. Participants were 149 men and 120 postmenopausal women 50 to 65 years of age who were sedentary and free of cardiovascular disease. Recruitment was achieved through a random digit-dial community telephone survey and media promotion. All exercise occurred in community settings. For higher-intensity exercise training, three 40-minute endurance training sessions per week were prescribed at 73% to 88% of peak treadmill heart rate. For lower-intensity exercise, five 30-minute endurance training sessions per week were prescribed at 60% to 73% of peak treadmill heart rate. Treadmill exercise performance, lipoprotein levels and other heart disease risk factors, and exercise adherence were evaluated at baseline and across the 2-year period. Treadmill exercise test performance improved for all three training conditions during year 1 and was successfully maintained during year 2, particularly for subjects in the higher-intensity, home-based condition. Subjects in that condition also showed the greatest year 2 exercise adherence rates (P < .003). Although no significant increases in HDL cholesterol were observed during year 1, by the end of year 2 subjects in the two home-based training conditions showed small but significant HDL cholesterol increases over baseline (P < .01). The increases were particularly pronounced for subjects in the lower-intensity condition, whose exercise prescription required more frequent exercise sessions per week. For all exercise conditions, increases in HDL cholesterol were associated with decreases in waist-to-hip ratio in both men and women (P < .04).\n While older adults can benefit from initiating a regular regimen of moderate-intensity exercise in terms of improved fitness levels and small improvements in HDL cholesterol levels, the time frame needed to achieve HDL cholesterol change (2 years) may be longer than that reported previously for younger populations. Frequency of participation may be particularly important for achieving such changes. Supervised home-based exercise regimens represent a safe, attractive alternative for achieving sustained participation.", "Supervised, hospital-based exercise rehabilitation programs are effective for improving functional status for patients with claudication due to peripheral arterial occlusive disease. However, it has been suggested that unsupervised, home-based exercise programs, which have been relatively little evaluated, would be equally efficacious as compared with hospital-based programs. The authors tested the hypothesis that a hospital-based exercise rehabilitation program would improve treadmill exercise performance more than a home-based program. Of 20 consecutively enrolled patients with claudication, 10 were randomly placed into a supervised, hospital-based program and 10 into an unsupervised, home-based program for a three-month period. Exercise performance was evaluated by treadmill testing using a graded protocol. In addition, functional status was evaluated by the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study SF-20 questionnaire (MOS). Patients in the hospital-based program were treated with treadmill walking three times a week for one hour/visit. Patients in the home-based program were instructed to walk at least three times a week and were contacted weekly to provide encouragement and to record compliance with the program. Patients in the hospital-based group improved peak walking time by 137%, pain-free walking time by 150%, and peak oxygen consumption by 19% (all P < 0.05). Patients reported an improved walking distance and speed according to WIQ data (both P < 0.05). In addition, the MOS physical functioning score in the hospital-based group improved by 20 percentage points (P < 0.05). In contrast, patients in the home-based program did not improve exercise performance measured on the treadmill. Improvement in the ability to walk on the treadmill was greater in the hospital-based than the home-based program (P < 0.05). The ability to walk distances was the only questionnaire measure that improved in persons who received the home-based program (P < 0.05). Preliminary results suggest that a supervised, hospital-based program is more effective for improving treadmill exercise performance than an unsupervised, home-based program.", "This study was performed to test the effectiveness of a formal supervised exercise program against a home-based exercise program for both walking ability and quality of life endpoints.\n Patients with arterial claudication were randomized to either a 12-week supervised exercise program (SUPEX) with weekly lectures relating to peripheral vascular disease or to a home exercise group (HOMEX) who attended an identical lecture program and received weekly exercise instruction. The study population included 29 men and 26 women, with a mean age of 69.1 +/- 8.1 years. Forty-seven patients completed the 12-week program, 46 were available for testing at completion, and 38 for 6-month testing. Claudication pain time (CPT) and maximum walking time (MWT) on a progressive treadmill exercise test were assessed at baseline, program completion, and 6 months. The Medical Outcomes Study Short Form-36 (SF-36) was administered at these intervals to assess effects on quality of life.\n Each group improved (p < 0.001) in both CPT and MWT at the completion of the 12-week program, which was sustained at the 6-month follow-up. Increase in HOMEX CPT from baseline (3.6 +/- 2.73 minutes) to 6-month follow-up (6.6 +/- 3.17 minutes) was less than for the SUPEX group (3.8 +/- 2.74 to 11.2 +/- 4.02 minutes, respectively); similar results were obtained for MWT. At both completion and 6 months, there was a significant intergroup difference for CPT and MWT (p < 0.004) favoring SUPEX. For both groups, measures of health perception based on the SF-36 demonstrated improvement (p < 0.002) in Physical Function Subscale, Bodily Pain Subscale, and Physical Composite Score. There were no between-group differences on the subsets of the SF-36 at the three assessment intervals.\n Supervised exercise programs provide superior increased walking ability in the noninterventional therapy of arterial claudication, and both supervised and home based exercise therapy result in improved SF-36 functional measures. The lack of intergroup differences in these measures may be a result of the high degree of interaction with healthcare providers in the HOMEX group. Although a supervised program results in optimal walking benefits, a highly structured home-based program provides similar functional improvement and may be a satisfactory alternative for patients with lesser walking requirements." ]

[ "1739177", "9687996", "16041208", "12145577", "8725454", "3103731", "2039294", "9449869", "8535807", "8598755" ]

[ "Precholecystectomy endoscopic cholangiography and stone removal is not superior to cholecystectomy, cholangiography, and common duct exploration.", "Surgery vs endoscopy as primary treatment in symptomatic patients with suspected common bile duct stones: a multicenter randomized trial. French Associations for Surgical Research.", "Postoperative ERCP versus laparoscopic choledochotomy for clearance of selected bile duct calculi: a randomized trial.", "Laparoscopic common bile duct exploration and cholecystectomy versus endoscopic stone extraction and laparoscopic cholecystectomy for choledocholithiasis. A prospective randomized study.", "Prospective randomized trial comparing endoscopic sphincterotomy followed by surgery with surgery alone in good risk patients with choledocholithiasis.", "Prospective randomised study of preoperative endoscopic sphincterotomy versus surgery alone for common bile duct stones.", "Choledocholithiasis. Endoscopic sphincterotomy or common bile duct exploration.", "Randomised trial of laparoscopic exploration of common bile duct versus postoperative endoscopic retrograde cholangiography for common bile duct stones.", "Long-term follow-up of a prospective randomized study of endoscopic versus surgical treatment of bile duct calculi in patients with gallbladder in situ.", "Randomised trial of endoscopic sphincterotomy with gallbladder left in situ versus open surgery for common bileduct calculi in high-risk patients." ]

[ "Thirty-four patients with suspected common bile duct stones were randomized to undergo endoscopic cholangiography and stone removal prior to open cholecystectomy or to have open cholecystectomy, operative cholangiography, and common bile duct exploration. Sixteen underwent the first protocol, and 18 the second. Analysis of the ability to clear stones from the common bile duct, morbidity, mortality, hospital stay, length of operation, and hospital cost showed no difference in outcome between patients treated by either method. These data suggest there is neither an advantage nor a disadvantage to treating patients with suspected duct stones by precholecystectomy endoscopic cholangiography and stone removal.", "To compare surgical treatment (ST) with endoscopic management (EM) in patients with suspected common bile duct stones.\n Two hundred twenty eligible patients originating from 18 surgery units. Patients enrolled in this multicenter randomized study had clinical symptoms that included jaundice, mild pancreatitis (Ranson score < or = 2), or mild acute cholangitis; biliary colic (with increased alkaline phosphatase levels); and common bile duct stones or a common bile duct diameter of 1 cm or larger on ultrasonography.\n Two hundred two patients were randomly assigned to either ST (n=105) or EM (n=97) during a 5-year period. Both groups were comparable with respect to age, sex, American Society of Anesthesiologists score, and clinical presentation.\n The rates of early postoperative additional procedures necessary to deal with the impossibility to perform the initial procedure, complications, and retained stones after ST or EM. Subsidiary endpoints were intention-to-treat analyses of mortality and of major complications and the duration of hospital stay.\n Surgical treatment was associated with a significantly (P<.001) lower rate of 1 or 2 additional procedures (8% vs 29%) due to a significantly lower rate of the impossibility to perform the initial procedure (0% vs 5%) (P<.05), major complications (4% vs 13%) (P<.05), and retained stones (6% vs 16%) (P<.04). Minor complications occurred more often in patients having ST (4%) than in those having EM (0%) (P<.01). Cholecystectomy was performed routinely in 102 patients having ST and electively in 36 patients having EM. There was 1 death in each group initially. On an intention-to-treat analysis, 3 deaths (3.1%) occurred after EM and 1 (0.9%) after ST; this difference was not statistically significant (P=.56). Major complications occurred in 4% of patients having ST compared with 1 1% of patients having EM (P<.002). The median duration of hospital stay was 16 days in patients having ST and 12 days in those having EM; this difference was not statistically significant (P=.09).\n Whether an additional cholecystectomy is performed routinely or electively, the high risk of additional procedures after EM precludes its use as the optimal therapy in patients with symptomatic common bile duct stones, except in those with severe cholangitis.", "Prospectively evaluate whether for patients having laparoscopic cholecystectomy with failed trans-cystic duct clearance of bile duct (BD) stones they should have laparoscopic choledochotomy or postoperative endoscopic retrograde cholangiography (ERCP).\n Clinical management of BD stones found at laparoscopic cholecystectomy in the last decade has focused on pre-cholecystectomy detection with ERCP clearance in those with suspected stones. This clinical algorithm successfully clears the stones in most patients, but no stones are found in 20% to 60% of patients and rare unpredictably severe ERCP morbidity can result in this group. Our initial experience of 300 consecutive patients with fluoroscopic cholangiography and intraoperative clearance demonstrated that, for the pattern of stone disease we see, 66% of patients' BD stones can be cleared via the cystic duct with dramatic reduction in morbidity compared to the 33% requiring choledochotomy or ERCP. Given the limitations of the preoperative approach to BD stone clearance, this trial was designed to explore the limitations, for patients failing laparoscopic trans-cystic clearance, of laparoscopic choledochotomy or postoperative ERCP.\n Across 7 metropolitan hospitals after failed trans-cystic duct clearance, patients were intraoperatively randomized to have either laparoscopic choledochotomy or postoperative ERCP. Exclusion criteria were: ERCP prior to referral for cholecystectomy, severe cholangitis or pancreatitis requiring immediate ERCP drainage, common BD diameter of less than 7 mm diameter, or if bilio-enteric drainage was required in addition to stone clearance. Drain decompression of the cleared BD was used in the presence of cholangitis, an edematous ampulla due to instrumentation or stone impaction and technical difficulties from local inflammation and fibrosis. The ERCP occurred prior to discharge from hospital. Mechanical and extracorporeal shockwave lithotripsy was available. Sphincter balloon dilation as an alternative to sphincterotomy to allow stone extraction was not used. Major endpoints for the trial were operative time, morbidity, retained stone rate, reoperation rate, and hospital stay.\n From June 1998 to February 2003, 372 patients with BD stones had successful trans-cystic duct clearance of stones in 286, leaving 86 patients randomized into the trial. Total operative time was 10.9 minutes longer in the choledochotomy group (158.8 minutes), with slightly shorter hospital stay 6.4 days versus 7.7 days. Bile leak occurred in 14.6% of those having choledochotomy with similar rates of pancreatitis (7.3% versus 8.8%), retained stones (2.4% versus 4.4%), reoperation (7.3% versus 6.6%), and overall morbidity (17% versus 13%).\n These data suggest that the majority of secondary BD stones can be diagnosed at the time of cholecystectomy and cleared trans-cystically, with those failing having either choledochotomy or postoperative ERCP. However, because of the small trial size, a significant chance exists that small differences in outcome may exist. We would avoid choledochotomy in ducts less than 7 mm measured at the time of operative cholangiogram and severely inflamed friable tissues leading to a difficult dissection. We would advocate choledochotomy as a good choice for patients after Billroth 11 gastrectomy, failed ERCP access, or where long delays would occur for patient transfer to other locations for the ERCP.", "Our objective is to compare the results of laparoscopic cholecystectomy (LC) and common bile duct (CBD) exploration to those of endoscopic stone extraction and LC in patients with CBD lithiasis based on a prospective randomized study.\n From April 1997 until August 2000, 78 patients were assigned in two groups. Group A (n'36) patients underwent laparoscopic either direct or trancystic duct, CBD exploration and LC. Group B (n'42) patients were referred for endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) for duct clearance and at a later stage LC was performed. Selection of patients of both groups was done, considering prognostic factors of a preliminary study.\n Laparoscopic duct clearance was achieved in 85.7% of patients while the respective percentage for the combined approach was 84.3%.\n Laparoscopic CBD exploration is not yet established as the gold standard procedure for choledocholithiasis and there is the need for further randomized trials and possibly future meta-analyses.", "Role of endoscopic sphincterotomy (ES) in high risk patients with choledocholithiasis is established but its role in good risk patients is unclear.\n A prospective randomized trial of endoscopic sphincterotomy followed by surgery (ES + S) versus surgery alone (SA) in good risk patients with choledocholithiasis.\n A tertiary level referral hospital in north India; July 1991 to October 1993.\n Thirty three out of 60 patients with choledocholithiasis were found suitable for randomization--16 were randomised to ES + S group and 17 to SA group.\n Common bile duct clearance was achieved in 11/13 (85%) patients in ES + S group and in 13/15 (87%) in SA group. Major complications occurred in 4/13 (31%) patients in ES + S group and 3/16 (19%) patients in SA group. These differences were not statistically significant, but patients in ES + S group were exposed to morbidity twice, procedure related morbidity of ES being 23%. No significant differences were observed in hospital stay and cost of treatment.\n Results of this trial do not support use of precholecystectomy ES in good risk patients with choledocholithiasis, since it did not offer any advantage over surgery alone.", "One hundred and twenty patients with known common bile duct stones were entered into a prospective randomised study of preoperative endoscopic sphincterotomy and stone clearance (group 1) versus surgery alone (group 2). Five patients were incorrectly entered; the 55 patients randomised to group 1 and the 60 randomised to group 2 were well matched with respect to clinical features and biochemical and medical risk factors. In group 1 endoscopic stone clearance was successful in 50 patients (91%); five of these patients refused elective surgery, though this was subsequently necessary in one. In group 2 common bile duct stones were cleared surgically in 54 of 59 patients (91.5%); one patient was treated by endoscopic sphincterotomy alone because of a myocardial infarct. The overall major complication rate in group 1 was 16.4% and included two deaths; in group 2 this was 8.5% and included one death. The minor complication rate in group 1 was 16.4% and that in group 2 13.6%. These differences in outcome were not significant. Despite a significant reduction in total hospital stay of patients in group 1, these results do not support the routine use of preoperative endoscopic sphincterotomy in patients having biliary surgery for stones in the common bile duct.", "A prospective randomized trial was conducted of preoperative endoscopic sphincterotomy and surgery (ES&S) or surgery alone (SA) in 52 patients with cholecystolithiasis and choledocholithiasis that were candidates for elective surgery. After ES&S 65% of patients were stone free. Eighty-eight per cent of patients with SA were stone free after surgery (p less than 0.05). Three patients in each group had residual stones at the completion of the operation. Five of these six had more than 20 common bile duct (CBD) stones. There was one episode of major hemorrhage in a patient in each group and no deaths. Costs were essentially equal for the individual patient with a successful ES as compared to SA. Societal costs of a program of preoperative endoscopic retrograde cholangiopancreatography and ES would be higher because of the cost of screening for patients with CBD stones. These results do not support preoperative ES as a technique for clearance of the CBD of stones on the basis of efficacy, morbidity rate, or cost.", "The management of stones in the common bile duct in the laparoscopic era is controversial. The three major options are preoperative endoscopic retrograde cholangiography (ERCP), laparoscopic exploration of the common bile duct (LECBD), or postoperative ERCP.\n Between August, 1995, and August, 1997, 471 laparoscopic cholecystectomies were done in our department. In 427 (91%), satisfactory peroperative cholangiography was obtained. In 80 (17%) of these cases there were stones in the common bile duct, 40 patients were randomised to LECBD and 40 to postoperative ERCP. If LECBD failed, patients had either open exploration of the common bile duct or postoperative ERCP. If one postoperative ERCP failed, the procedure was repeated until the common bile duct was cleared of stones or an endoprosthesis was placed to prevent stone impaction. The primary endpoints were duct-clearance rates, morbidity, operating time, and hospital stay. Analyses were by intention to treat.\n Age and sex distribution of patients was similar in the randomised groups. Duct clearance after the first intervention was 75% in both groups. By the end of treatment, duct clearance was 100% in the laparoscopic group compared with 93% in the ERCP group. Duration of treatment was a median of 90 min (range 25-310) in the laparoscopic group (including ERCPs for failed LECBD) compared with 105 min (range 60-255) in the postoperative ERCP group (p = 0.1, 95% CI for difference -5 to 40). Hospital stay was a median of 1 day (range 1-26) in the laparoscopic group compared with 3.5 days (range 1-11) in the ERCP group (p = 0.0001, 95% CI 1-2).\n LECBD is as effective as ERCP in clearing the common bile duct of stones. There is a non-significant trend to shorter time in the operating theatre and a significantly shorter hospital stay in patients treated by LECBD.", "Eighty-three patients with bile duct calculi were entered in a prospective randomized study of endoscopic sphincterotomy (ES) and stone removal (group 1) versus surgery alone (group 2), and were followed for more than 5 years. In group 1 endoscopic stone clearance was successful in 35 of 39 patients. Thirteen patients subsequently had cholecystectomy with (n = 7) or without (n = 6) biliary symptoms and one had a cholecystostomy for acute cholecystitis. Two patients have had mild biliary colic or pancreatitis. Two patients died from gallbladder carcinoma after 9 days and 18 months. In group 2 bile duct stones were cleared surgically in 37 of 41 patients. Late complications occurred in two patients (incisional hernia and recurrent stone). One patient with gallbladder carcinoma was cured and another died after 16 months. Early major and minor complications occurred in three and four respectively of 39 patients in group 1, and in three and six respectively of 41 patients in group 2. There were no deaths. During follow-up the total morbidity rate reached 28 percent (11 of 39) and 5 percent (two of 41) (P = 0.005) and the non-biliary related mortality rate was 31 percent (12 of 39) and 10 percent (four of 41) (P = 0.02) in groups 1 and 2 respectively. Nine patients in group 1 and two in group 2 died from heart disease (P = 0.02). Total hospital stay was 2-42 (median 13) days and 6-36 (median 16) days in groups 1 and 2 respectively (P not significant). Endoscopic and surgical treatment of bile duct calculi in middle-aged and elderly patients with gallbladder in situ are equally effective in the long term. However, the significantly increased mortality rate from heart disease in patients treated endoscopically compared with those treated surgically might speak in favour of operation.", "Morbidity and mortality after surgical treatment of bileduct stones increase with age and associated diseases. A proposed alternative therapy is endoscopic sphincterotomy (ES) with the gallbladder left in situ, and we elected to compare this option with standard open surgery in high-risk patients.\n 98 patients (mean age 80 years) with symptoms likely to be due to bileduct stones or a recent episode of biliary pancreatitis were randomised to be treated either by open cholecystectomy with operative cholangiography and (if necessary) bileduct exploration (n=48) or by endoscopic sphincterotomy alone (n=50).\n The procedure was accomplished successfully in 94% of the surgery group and 88% of the ES group, and there were no significant differences in immediate morbidity (23% vs 16%) or mortality (4% vs 6%). During mean follow-up of 17 months biliary symptoms recurred in three surgical patients, none of whom underwent repeat surgery, and in 10 ES patients, seven of whom had biliary surgery. By multivariate regression analysis endoscopic sphincterotomy was an independent predictor of recurrent biliary symptoms (odds ratio 6.9; 95% Cl 1.46 to 32.54).\n In elderly or high-risk patients, surgery is preferable to endoscopic sphincterotomy with the gallbladder left in situ as a definitive treatment for bileduct stones or non-severe biliary pancreatitis." ]

[ "10072411", "18679151", "9332329", "10864055", "15530193", "9709879" ]

[ "Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group.", "Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial.", "A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients.", "Use of amphotericin B colloidal dispersion in children.", "Randomized comparison between fluconazole and itraconazole for the treatment of candidemia in a pediatric intensive care unit: a preliminary study.", "Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia." ]

[ "In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity.\n We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy.\n The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P=0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P<0.001).\n Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity.", "Invasive candidiasis is increasingly prevalent in premature infants and seriously ill children, and pediatric data on available antifungal therapies are lacking.\n We conducted a pediatric substudy as part of a double-blind, randomized, multinational trial to compare micafungin (2 mg/kg) with liposomal amphotericin B (3 mg/kg) as first-line treatment of invasive candidiasis. Treatment success was defined as clinical and mycologic response at the end of therapy. Statistical analyses were descriptive, as the sample size meant that the study was not powered for hypothesis testing.\n One hundred six patients were included in the intent-to-treat population; and 98 patients-48 patients in the micafungin group and 50 patients in the liposomal amphotericin B group-in the modified intent-to-treat population. Baseline characteristics were balanced between treatment groups. Overall, 57 patients were <2 years old including 19 patients who were premature at birth; and 41 patients were 2 to <16 years old. Most patients (91/98, 92.9%) had candidemia, and 7/98 (7.1%) patients had other forms of invasive candidiasis. Treatment success was observed for 35/48 (72.9%) patients treated with micafungin and 38/50 (76.0%) patients treated with liposomal amphotericin B. The difference in proportions adjusted for neutropenic status was -2.4% [95% CI: (-20.1 to 15.3)]. Efficacy findings were consistent, independent of the neutropenic status, the age of the patient, and whether the patient was premature at birth. Both treatments were well tolerated, but with a lower incidence of adverse events that led to discontinuation in the micafungin group (2/52, 3.8%) compared with the liposomal amphotericin B group (9/54, 16.7%) (P = 0.05, Fisher exact test).\n Micafungin seems to be similarly effective and as safe as liposomal amphotericin B for the treatment of invasive candidiasis in pediatric patients. (ClinicalTrials.gov number, NCT00106288).", "One hundred and thirty-four adults and 204 children were randomized in two prospective, parallel comparative multicentre trials to receive either conventional amphotericin B 1 mg/kg/d (c-AMB), liposomal amphotericin B 1 mg/kg/d(L-AMB1) or liposomal amphotericin B 3 mg/ kg/d (L-AMB3). Patients were entered if they had a pyrexia of unknown origin (PUO) defined as temperature of 38 degrees C or more, not responding to 96 h of systemic broad-spectrum antibiotic treatment, and neutropenia (< 0.5 x 10(9)/l). The safety and toxicity of liposomal amphotericin B was compared with that of conventional amphotericin B. Efficacy of treatment was assessed, with success defined as resolution of fever for 3 consecutive days (< 38 degrees C) without the development of any new fungal infection. Clinical and laboratory parameters were collected for safety analysis. In both the paediatric and adult populations, L-AMB treated patients had a 2-6-fold decrease in the incidence (P < or = 0.01) of test-drug-related side-effects, compared to c-AMB. Severe trial-drug-related side-effects were seen in 1% of L-AMB treated patients, in contrast to 12% of patients on c-AMB (P < 0.01). Nephrotoxicity, in the patient subset not receiving concomitant nephrotoxic agents, defined as a doubling from the patients baseline serum creatinine level, was not observed in the L-AMB1 arm whereas the incidence was 3% in patients on L-AMB3 and 23% in those on c-AMB (P < 0.01). Moreover, time to develop nephrotoxicity was longer in both L-AMB arms than c-AMB (P < 0.01). Severe hypokalaemia was observed less frequently in both L-AMB arms (P < 0.01). Analysis was by intention-to-treat and included all patients randomized. Success was defined by a minimum of 3 consecutive days with fever (< 38 degrees C) continuing to study end indicated by recovery of neutrophils to 0.5 x 10(9)/l. Addition of systemic antifungal therapy or development of systemic fungal infection were failures as was persistent fever to study end. Efficacy assessments indicated success in 49% of the total group treated with c-AMB, 58% of patients responded to L-AMB1 and 64% to L-AMB3. A statistically significant difference was found between c-AMB and L-AMB3 (P = 0.03) but a Kaplan-Meier analysis of time to differvescence of fever showed there was no significant difference between the arms. It was concluded that liposomal amphotericin at either 1 or 3 mg/kg/d was significantly safer than conventional amphotericin B in children and adults. The main aim of this open-label study was to compare safety between the three trial arms. However, we provide evidence for an equivalent or possibly superior efficacy of liposomal amphotericin with regard to resolution of fever of unknown origin. Subsequent trials should compare amphotericin preparations in defined fungal infections.", "To describe the experience with a new lipid-based amphotericin product (amphotericin B colloidal dispersion or ABCD) in children with fever and neutropenia who are at high risk for fungal infection.\n Forty-nine children with febrile neutropenia were treated in a prospective, randomized trial comparing ABCD with amphotericin B. An additional 70 children with presumed or proven fungal infection were treated with 5 different open-label studies of ABCD. Patients were registered into these studies for reasons of: 1) failure to respond to amphotericin B; 2) development of nephrotoxicity or preexisting renal impairment; or 3) willingness to participate in a dose-escalation study. Extensive data detailing response and toxicity were collected from each patient.\n In the randomized trial, there was significantly less renal toxicity in the children receiving ABCD than in those receiving amphotericin B (12.0% vs. 52.4% [P = 0.003]). Other adverse symptoms were not significantly different. In the additional open-label studies, although 80% of patients receiving ABCD reported some adverse symptom, the majority of these were infusion related, and nephrotoxicity was reported in only 12% of these patients.\n ABCD was well-tolerated at doses up to 5 times greater then those usually tolerated with amphotericin B. Renal toxicity was markedly less than expected, and there were no other unexpected severe toxicities. Further randomized studies are needed to further define the role of this and other liposomal products in children.", "Candida bloodstream infections have shown an increase in hospitalized patients, especially those receiving intensive care. The effectiveness of various azoles, especially itraconazole, in treatment of candidemia has not been fully evaluated. Our objective was to compare the efficacy and safety of enterally administered itraconazole vs. fluconazole in treatment of candidemia.\n Randomized, double-blind, controlled trial.\n Pediatric intensive care unit of a referral and teaching hospital.\n Forty-three pediatric patients with candidemia,\n Patients received either fluconazole (n = 22) or itraconazole (n = 21), about 10 mg/kg orally or through a gastric tube, and were monitored for clinical and mycological cure (sterile fungal blood culture), blood counts, and liver and renal functions.\n The clinical characteristics of two groups were comparable. The cure rate was similar in both the groups: itraconazole 17 of 21 (81%) and fluconazole 18 of 22 (82%). Crude mortality rate (itraconazole 9.5% and fluconazole 13.6%) was also comparable in two groups of patients. The frequency of electrolyte disturbance was very low and similar in both the groups. Blood urea, creatinine, liver enzymes, and serum bilirubin were not adversely affected.\n Itraconazole was as effective as fluconazole in nosocomial candidiasis in children receiving intensive care and was devoid of serious side effects.", "We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment." ]

[ "20776417", "7901636", "12495257", "12173139", "10465076", "20435345", "11303488", "12097669", "10037634", "12891825", "15956998", "16359410", "16579803", "5889786", "11488938", "15531679" ]

[ "DIET AS A PROPHYLACTIC AGENT AGAINST PUERPERAL SEPSIS.", "Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia.", "Effect of low-dosage vitamin A and riboflavin on iron-folate supplementation in anaemic pregnant women.", "Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi.", "Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group.", "Effect of vitamin A supplementation in women of reproductive age on maternal survival in Ghana (ObaapaVitA): a cluster-randomised, placebo-controlled trial.", "Weekly supplementation with iron and vitamin A during pregnancy increases hemoglobin concentration but decreases serum ferritin concentration in Indonesian pregnant women.", "Vitamin A and iron status are improved by vitamin A and iron supplementation in pregnant Indonesian women.", "Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in Nepal. The NNIPS-2 Study Group.", "Red palm oil supplementation: a feasible diet-based approach to improve the vitamin A status of pregnant women and their infants.", "Effect of vitamin supplementation to HIV-infected pregnant women on the micronutrient status of their infants.", "Maternal vitamin A supplementation and immunity to malaria in pregnancy in Ghanaian primigravids.", "Randomised trial of vitamin A supplementation in pregnant women in rural Malawi found to be anaemic on screening by HemoCue.", "Inluence of vitamin A on human colostrum and early milk.", "Impact of vitamin A supplementation on anaemia and plasma erythropoietin concentrations in pregnant women: a controlled clinical trial.", "Zinc plus beta-carotene supplementation of pregnant women is superior to beta-carotene supplementation alone in improving vitamin A status in both mothers and infants." ]

[ "nan", "Nutritional anaemia, thought to be caused by iron deficiency, affects 50-70% of pregnant women in the developing world. The influence of vitamin A and iron supplementation was studied in anaemic pregnant women in West Java, in a randomised, double-masked, placebo-controlled field trial. 251 women aged 17-35 years, parity 0-4, gestation 16-24 weeks, and haemoglobin between 80 and 109 g/L were randomly allocated to four groups: vitamin A (2.4 mg retinol) and placebo iron tablets; iron (60 mg elemental iron) and placebo vitamin A; vitamin A and iron; or both placebos, all daily for 8 weeks. Maximum haemoglobin was achieved with both vitamin A and iron supplementation (12.78 g/L, 95% Cl 10.86 to 14.70), with one-third of the response attributable to vitamin A (3.68 g/L, 2.03 to 5.33) and two-thirds to iron (7.71 g/L, 5.97 to 9.45). After supplementation, the proportion of women who became non-anaemic was 35% in the vitamin-A-supplemented group, 68% in the iron-supplemented group, 97% in the group supplemented with both, and 16% in the placebo group. Improvement in vitamin A status may contribute to the control of anaemic pregnant women.", "A double-blind, placebo, controlled trial was conducted in Banyudono subdistrict, Boyolali regency, Central Java province, Indonesia. The aim of the study was to determine whether adding low-dosage vitamin A and riboflavin can enhance the effect of iron-folate supplementation in anaemic pregnant women. From July to November 2000, 202 pregnant women were screened for anaemia (haemoglobin < 11.0 g/dL). One hundred and three pregnant women (51%) were found to be anaemic and were then allocated alternately into four groups. Over a period of 60 days, group IF (n = 29) received iron-folate tablets (200 mg FeSO4 and 250 microg folic acid) + 5 mg glucose: group IFR (n = 22) received iron-folate tablets + 5 mg riboflavin; group IFA (n = 29) received iron-folate tablets + 2.75 mg retinyl palmitate (equal to 5000 IU vitamin A); and group IFRA (n = 23) received iron-folate tablets + 5 mg riboflavin + 2.75 mg retinyl palmitate. At the end of the study 19 pregnant women (18.4%) were excluded from the analysis because of various reasons. Statistical analysis was based on 84 women (81.5%): group IF, n = 25; group IFR, n = 22; group IFA, n = 18; and group IFRA, n = 19. Haemoglobin measurements were carried out using the Technicon H1* (cyanmethaemoglobin method). All groups showed a significant increase in haemoglobin concentration (P < 0.05), except group IFA (P > 0.05), with the highest increment being in group FR. Multiple comparisons only showed significant differences between group IFR and group IFA (P < 0.05). It can be concluded that iron-folate supplementation can increase haemoglobin concentrations in anaemic pregnant women. Adding riboflavin tends to enhance the effect of iron-folate supplementation, but this is not the case with adding vitamin A.", "Vitamin A is essential for immunity and growth. A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia, low birth weight, growth failure, HIV transmission, and mortality. Women received daily doses of iron and folate, either alone or combined with vitamin A (3 mg retinol equivalent), from 18-28 weeks' gestation until delivery. In the vitamin A and control groups, respectively, the mean (+/-SE) birth weights were 2895+/-31 g and 2805+/-32 g (P=.05), the proportions of low-birth-weight infants were 14.0% and 21.1% (P=.03), the proportions of anemic infants at 6 weeks postpartum were 23.4% and 40.6% (P<.001), and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6% and 27.8% (P=.76) and 27.7% and 32.8% (P=.21). Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia, but it did not affect perinatal HIV transmission.", "Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome. We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1.\n In Durban, South Africa 728 pregnant HIV infected women received either vitamin A (368) or placebo (360) in a randomized, double-blind trial. The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery. HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis. Results are reported on mother-to-child transmission rates up to 3 months of age.\n There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [20.3%; 95% confidence interval (CI), 15.7-24.9] and placebo groups (22.3%; 95% CI, 17.5-27.1), nor were there differences in foetal or infant mortality rates between the two groups. Women receiving vitamin A supplement were, however, less likely to have a preterm delivery (11.4% in the vitamin A and 17.4% in the placebo group; P = 0.03) and among the 80 preterm deliveries, those assigned to the vitamin A group were less likely to be infected (17.9%; 95% CI, 3.5-32.2) than those assigned to the placebo group (33.8%; 95% CI, 19.8-47.8).\n Vitamin A supplementation, a low-cost intervention, does not appear to be effective in reducing overall mother-to-child transmission of HIV; however, its potential for reducing the incidence of preterm births, and the risk of mother-to-child transmission of HIV in these infants needs further investigation.", "A previous trial in Nepal showed that supplementation with vitamin A or its precursor (betacarotene) in women of reproductive age reduced pregnancy-related mortality by 44% (95% CI 16-63). We assessed the effect of vitamin A supplementation in women in Ghana.\n ObaapaVitA was a cluster-randomised, double-blind, placebo-controlled trial undertaken in seven districts in Brong Ahafo Region in Ghana. The trial area was divided into 1086 small geographical clusters of compounds with fieldwork areas consisting of four contiguous clusters. All women of reproductive age (15-45 years) who gave informed consent and who planned to remain in the area for at least 3 months were recruited. Participants were randomly assigned by cluster of residence to receive a vitamin A supplement (25 000 IU retinol equivalents) or placebo capsule orally once every week. Randomisation was blocked and based on an independent, computer-generated list of numbers, with two clusters in each fieldwork area allocated to vitamin A supplementation and two to placebo. Capsules were distributed during home visits undertaken every 4 weeks, when data were gathered on pregnancies, births, and deaths. Primary outcomes were pregnancy-related mortality and all-cause female mortality. Cause of death was established by verbal post mortems. Analysis was by intention to treat (ITT) with random-effects regression to account for the cluster-randomised design. Adverse events were synonymous with the trial outcomes. This trial is registered with ClinicalTrials.gov, number NCT00211341.\n 544 clusters (104 484 women) were randomly assigned to vitamin A supplementation and 542 clusters (103 297 women) were assigned to placebo. The main reason for participant drop out was migration out of the study area. In the ITT analysis, there were 39 601 pregnancies and 138 pregnancy-related deaths in the vitamin A supplementation group (348 deaths per 100 000 pregnancies) compared with 39 234 pregnancies and 148 pregnancy-related deaths in the placebo group (377 per 100 000 pregnancies); adjusted odds ratio 0.92, 95% CI 0.73-1.17; p=0.51. 1326 women died in 292 560 woman-years in the vitamin A supplementation group (453 deaths per 100 000 years) compared with 1298 deaths in 289 310 woman-years in the placebo group (449 per 100 000 years); adjusted rate ratio 1.01, 0.93-1.09; p=0.85.\n The body of evidence, although limited, does not support inclusion of vitamin A supplementation for women in either safe motherhood or child survival strategies.\n UK Department for International Development, and USAID.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "We investigated whether weekly iron supplementation was as effective as the national daily iron supplementation program in Indonesia in improving iron status at near term in pregnancy. In addition, we examined whether weekly vitamin A and iron supplementation was more efficacious than weekly supplementation with iron alone. One group of pregnant women (n = 122)was supplemented weekly with iron (120 mg Fe as FeSO4) and folic acid (500 microg); another group (n = 121) received the same amount of iron and folic acid plus vitamin A [4800 retinol equivalents (RE)]. A third (\"daily\") group (n = 123), participating in the national iron plus folic acid supplementation program, was also recruited. Data on subjects with complete biochemical data are reported (n = 190). At near term, hemoglobin concentrations increased, whereas serum ferritin concentrations decreased significantly in the weekly vitamin A and iron group, suggesting that vitamin A improved utilization of iron for hematopoiesis. Iron status in the weekly iron group was not different from that of the \"daily\" group. However, iron status decreased with daily supplementation if <50 iron tablets were ingested. Serum transferrin receptor concentrations increased in all groups (P < 0.01). Serum retinol concentrations were maintained in the weekly vitamin A and iron group, but decreased in the other two groups (P < 0.01). Thus, delivery of iron supplements on a weekly basis can be as effective as ona daily basis if compliance can be ensured. Addition of vitamin A to the supplement improved hemoglobin concentration.", "In Indonesia, deficiencies of vitamin A and iron are of public health concern during pregnancy. We sought to determine the effects of vitamin A and iron supplementation on the vitamin A and iron status of pregnant Indonesian women. The women (n = 27) were randomly assigned to four groups. The modified relative dose response (MRDR) test for vitamin A status and hemoglobin, hematocrit and ferritin values were determined at baseline. Thereafter, daily supplements were administered: placebo [Pl] (n = 7), 8.4 micromol vitamin A [A] (n = 7), 1.07 mmol iron [Fe] (n = 5), and 8.4 micromol vitamin A plus 1.07 mmol iron [A + Fe] (n = 8). Post-treatment tests were performed after 8 wk. The MRDR value was reduced, i.e., vitamin A status improved, more markedly by the combination of vitamin A and iron than by either nutrient alone (P = 0.034). The decrease in the MRDR relative to baseline was significant in the A + Fe group (P = 0.008). Iron status was also significantly improved in these women (P < 0.05) with both iron and vitamin A supplementation. The mechanism of the enhancing effect of iron on the vitamin A-induced reduction in the MRDR is not known.", "To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as beta carotene.\n Double blind, cluster randomised, placebo controlled field trial.\n Rural southeast central plains of Nepal (Sarlahi district).\n 44 646 married women, of whom 20 119 became pregnant 22 189 times.\n 270 wards randomised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo, vitamin A (7000 micrograms retinol equivalents) or beta carotene (42 mg, or 7000 micrograms retinol equivalents) for over 31/2 years.\n All cause mortality in women during pregnancy up to 12 weeks post partum (pregnancy related mortality) and mortality during pregnancy to 6 weeks postpartum, excluding deaths apparently related to injury (maternal mortality).\n Mortality related to pregnancy in the placebo, vitamin A, and beta carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yielding relative risks (95% confidence intervals) of 0. 60 (0.37 to 0.97) and 0.51 (0.30 to 0.86). This represented reductions of 40% (P<0.04) and 49% (P<0.01) among those who received vitamin A and beta carotene. Combined, vitamin A or beta carotene lowered mortality by 44% (0.56 (0.37 to 0.84), P<0.005) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births, or by 40% (P<0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups.\n Supplementation of women with either vitamin A or beta carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia.", "This double-blinded, randomized, controlled study was designed to study the effect of dietary supplementation with red palm oil during pregnancy on maternal and neonatal vitamin A status. A total of 170 women were recruited at 16 to 24 weeks of gestation and randomly assigned to an experimental group that received red palm oil to supply approximately one recommended dietary amount (RDA) (2,400 micrograms) of beta-carotene or to a control group that received an equivalent volume of groundnut oil. The women received the oils for a period of 8 weeks, starting at 26 to 28 weeks of gestation and extending to 34 to 36 weeks of gestation. The mean postintervention (34 to 36 weeks) levels of serum retinol were 1.20 +/- 0.22 (SD) mumol/L (95% CI, 1.15-1.25) in women receiving red palm oil and 0.73 +/- 0.15 mumol/L (95% CI, 0.69-0.77) in their infants; these levels were significantly higher than those in women receiving groundnut oil (1.07 +/- 0.26 mumol/L; 95% CI, 1.01-1.13; p < .01) and their infants (0.62 +/- 0.17 mumol/L; 95% CI, 0.57-0.67; p < .001). A significantly lower proportion of women in the red palm oil group than in the control group had vitamin A deficiency (serum retinol levels < 0.7 mumol/L) after intervention (1.5% vs. 9.7%). The proportion of women having anemia was significantly lower (p < .01) in the red palm oil-supplemented group (80.6%) than in the control group (96.7%). The mean birthweight and gestational age of the infants did not differ significantly between the two groups. An increased risk of low birth-weight (p = .003) and preterm delivery (p = .000) was observed with decreasing serum retinol levels in the third trimester of pregnancy. These results show that red palm oil supplementation significantly improved maternal and neonatal vitamin A status and reduced the prevalence of maternal anemia. Maternal vitamin A status in the later part of pregnancy is significantly associated with fetal growth and maturation. Hence red palm oil, a rich source of bioavailable vitamin A, could be used as a diet-based approach for improving vitamin A status in pregnancy.", "We examined whether supplementation with vitamin A and/or vitamins B, C, and E to HIV-infected women during pregnancy and lactation is related to increased concentrations of vitamins A, B12, and E in their infants during the first 6 months of life.\n We carried out a randomized clinical trial among 716 mother-infant pairs in Dar-es-Salaam, Tanzania. Women were randomly allocated to receive a daily oral dose of one of four regimens: vitamin A, multivitamins (B, C, and E), multivitamins including A, or placebo. Supplementation started at first prenatal visit and continued after delivery throughout the breastfeeding period. The serum concentration of vitamins A, E and B12 was measured in infants at 6 weeks and 6 months postpartum.\n Maternal vitamin A supplementation increased serum retinol in the infants at 6 weeks (mean difference=0.09 micromol/l, P<0.0001) and 6 months (mean difference=0.06 micromol/l, P=0.0002), and decreased the prevalence of vitamin A deficiency, but had no impact on serum vitamins E or B12. Multivitamins increased serum vitamin B12 at 6 weeks and 6 months (mean differences=176 pmol/l, P<0.0001 and 127 pmol/l, P<0.0001, respectively) and vitamin E (mean differences=1.8 micromol/l, P=0.0008 and 1.1 micromol/l, P=0.004, respectively) and decreased the prevalence of vitamin B12 deficiency.\n Vitamin supplementation to HIV-1-infected women is effective in improving the vitamin status of infants during the first 6 months of age.", "Vitamin A supplementation is believed to enhance immune responses to infection but few studies have assessed its effects on anti-malarial immunity, especially during pregnancy when women are at increased risk from both vitamin A deficiency and pregnancy-associated malaria. The pathological effects of malaria in pregnancy are believed to be due to the sequestration of parasites in the placenta mediated via binding of variant surface antigens (VSA) expressed on the surface of P. falciparum infected red blood cells to placental chondroitin sulphate A (CSA).\n We conducted a randomized double-blind controlled trial of vitamin A supplementation in 98 primigravid Ghanaian women to investigate the effects of vitamin A supplementation on levels of IgG antibodies binding to VSA of a clinical, P. falciparum placental isolate and to two isolates selected (or not) for adherence to CSA in vitro (anti-VSACSA IgG or anti-VSA IgG). Placental malarial infection was determined by placental blood smear and histology.\n Vitamin A supplementation was non-significantly associated with a decreased risk of active or chronic-active placental malarial infection compared to past, resolved infection at delivery, as determined by histology (OR=0.42, P=0.13--adjusted for level of education). After adjustment for differences in baseline values, levels of anti-VSACSA IgG to a placental, CSA-adherent isolate (EJ-24) but not to two isolates selected for CSA-adhesion in vitro (FCR3CSA and BusuaCSA), were significantly lower in women receiving vitamin A supplementation than in women receiving placebo (P=0.002). There was no apparent effect of vitamin A supplementation to levels of Ab to non-CSA-adherent parasite isolates.\n The data suggest that the reduction in the levels of anti-VSACSA antibodies to the known placental malaria isolate may reflect reduced intensity or duration of placental parasitaemia in women receiving vitamin A supplementation. These observations are of potential public health significance and deserve further investigation.", "To assess the effects of vitamin A supplementation in women with anaemia during pregnancy.\n Single-centre randomised controlled trial.\n Rural community in southern Malawi, central Africa.\n Seven hundred women with singleton pregnancies at 12-24 weeks measured by ultrasound scan and with haemoglobin <11.0 g/dl by HemoCue screening method. Analysis was by intention to treat. All received iron and folate, and sulphadoxine/pyrimethamine for antimalarial prophylaxis.\n Women were randomised to receive oral supplementation with daily 5000 or 10,000 iu vitamin A, or placebo.\n Anaemia, as assessed by Coulter counter, severe anaemia, iron status and indices of infection.\n Vitamin A deficiency was, in this rural population, less common than predicted. Vitamin A supplementation had no significant impact on anaemia, severe anaemia, iron status and indices of infection. Vitamin A stores were less likely to be depleted at the end of pregnancy in supplemented groups.\n Vitamin A supplementation programmes to reduce anaemia should not be implemented in similar antenatal populations in rural sub-Saharan Africa unless evidence emerges of positive benefit on substantive clinical outcomes. Introducing public health interventions of unknown benefit and with unclear biological mechanisms can divert scarce resources from clinical and social interventions more likely to impact maternal mortality.", "nan", "Although studies suggest that vitamin A or its metabolites influence the synthesis of erythropoietin in vitro and in animal models, it is unclear whether vitamin A supplementation increases plasma erythropoietin concentrations in humans.\n To determine whether daily vitamin A supplementation increases plasma erythropoietin concentrations in pregnant women with a high prevalence of anaemia.\n A randomized, double-blind, controlled clinical trial was conducted to examine the effect of daily vitamin A (3000 microg retinol equivalent), iron (30 mg), and folate (400 microg) versus iron (30 mg) and folate (400 microg) (control) on haemoglobin and plasma erythropoietin concentrations in 203 pregnant women in Malawi, Africa.\n Mean gestational age at enrollment was 23 wk, at which time 50% of the women were anaemic (haemoglobin <110 g/L). Mean (+/-SEM) change in haemoglobin from enrollment to 38 wk was 4.7+/-1.6 g/L (p=0.003) and 7.3+/-2.3 g/L (p=0.003) in the vitamin A and control groups, respectively. Mean change in plasma erythropoietin concentrations from enrollment to 38 wk was 2.39+/-5.00 (p=0.63) and -2.87+/-3.92 IU/L (p=0.46) in the vitamin A and controls groups, respectively. There were no significant differences between vitamin A and control groups in the slope of the regression line between log10 erythropoietin and haemoglobin at enrollment or 38 wk, and between enrollment and follow-up within either group.\n Vitamin A supplementation does not appear to increase haemoglobin and plasma erythropoietin concentrations among pregnant women with a high prevalence of anaemia in Malawi.", "Deficiencies of vitamin A, iron, and zinc are prevalent in women and infants in developing countries. Supplementation during pregnancy can benefit mother and infant.\n We examined whether supplementation during pregnancy with iron and folic acid plus beta-carotene or zinc or both improves the micronutrient status of mothers and infants postpartum.\n Pregnant women (n = 170) were supplemented daily only during pregnancy with beta-carotene (4.5 mg), zinc (30 mg), or both or placebo plus iron (30 mg) and folic acid (0.4 mg) in a randomized, double-blind, placebo-controlled trial. Micronutrient status was assessed 1 and 6 mo postpartum.\n Six months postpartum, plasma retinol concentrations were higher in the women who received zinc during pregnancy than in women who did not. Infants born to mothers supplemented with beta-carotene + zinc had higher plasma retinol concentrations, with the frequency of vitamin A deficiency reduced by >30% compared with the other 3 groups. Breast-milk beta-carotene concentrations were higher in all women supplemented with beta-carotene, but breast-milk retinol concentrations were higher only in women who received beta-carotene + zinc. Zinc concentrations did not differ among groups in mothers and infants.\n Zinc supplementation during pregnancy improved the vitamin A status of mothers and infants postpartum, which indicates a specific role of zinc in vitamin A metabolism. Addition of both beta-carotene and zinc to iron supplements during pregnancy could be effective in improving the vitamin A status of mothers and infants." ]

[ "17050564" ]

[ "Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial." ]

[ "Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract infection in infancy. To date, there is no effective therapy for RSV bronchiolitis. In order to investigate the efficacy of clarithromycin in the treatment of RSV bronchiolitis, the present authors conducted a randomised, double-blind, placebo-controlled trial comparing clarithromycin with placebo in 21 infants with a diagnosis of RSV bronchiolitis. The infants were randomised to receive clarithromycin or placebo daily for 3 weeks. Levels of interleukin (IL)-4, IL-8, eotaxin, and interferon-gamma were determined in plasma, before and after treatment, using ELISA. Six months after treatment, parents were surveyed as to whether their child had experienced wheezing within the previous 6 months. Treatment with clarithromycin was associated with a statistically significant reduction in the length of hospital stay, the duration of need for supplemental oxygen and the need for beta(2)-agonist treatment. There were significant decreases in plasma IL-4, IL-8 and eotaxin levels after 3 weeks of treatment with clarithromycin. Readmission to the hospital within 6 months after discharge was significantly lower in the clarithromycin group. In conclusion, clarithromycin has statistically significant effects on the clinical and laboratory findings in respiratory syncytial virus bronchiolitis. Therefore, clarithromycin treatment may be helpful in reducing the short-term effects of respiratory syncytial virus bronchiolitis." ]

[ "16887443", "14634864", "1343079", "2264475" ]

[ "Early prednisone therapy in Henoch-Schönlein purpura: a randomized, double-blind, placebo-controlled trial.", "Henoch-Schönlein purpura nephritis: course of disease and efficacy of cyclophosphamide.", "Effectiveness of early prednisone treatment in preventing the development of nephropathy in anaphylactoid purpura.", "Prophylaxis and therapy of glomerulonephritis in the course of anaphylactoid purpura. The results of a polycentric clinical trial." ]

[ "To evaluate the efficacy of early prednisone therapy in preventing renal and treating extrarenal and renal symptoms in Henoch-Schönlein purpura (HSP) in a placebo-controlled trial.\n A total of 171 patients (84 treated with prednisone and 87 receiving placebo) were included and followed up for 6 months. The endpoints were renal involvement at 1, 3, and 6 months and healing of extrarenal symptoms. The analyses were performed on an intent-to-treat basis.\n Prednisone (1 mg/kg/day for 2 weeks, with weaning over the subsequent 2 weeks) was effective in reducing the intensity of abdominal pain (pain score, 2.5 vs 4.8; P = .029) and joint pain (4.6 vs 7.3; P = .030). Prednisone did not prevent the development of renal symptoms but was effective in treating them; renal symptoms resolved in 61% of the prednisone patients after treatment, compared with 34% of the placebo patients (difference = 27%; 95% confidence interval = 3% to 47%; P = .024).\n The general use of prednisone in HSP is not supported, but patients with disturbing symptoms may benefit from early treatment, because prednisone reduces extrarenal symptoms and is effective in altering (but not preventing) the course of renal involvement.", "Nephritis in Henoch-Schönlein purpura (HSP) is the primary cause of morbidity and mortality. Although many therapeutic regimens have been reported to be effective, no therapy has been shown in a controlled trial to be beneficial. Fifty-six patients with histopathologically severe HSP nephritis were randomized to receive supportive therapy with or without cyclophosphamide, 90 mg/m(2)/day for 42 days. Patients were classified according to status at final follow-up: Fully Recovered 48.2%, Persistent Abnormalities 39.3%, or ESRD/Death 12.5%. There were no differences in onset data or outcome between the two trial groups or in outcome between trial and 23 non-trial patients followed concurrently. Therefore, data from trial and non-trial patients were combined for further analysis. There was no correlation between outcome and age, blood pressure, serum total protein, or serum albumin. Although rates of proteinuria did not correlate with outcome, all those with progression to ESRD had nephrotic levels of proteinuria at onset. Only five of 28 patients with nephrotic levels of proteinuria and severe onset histopathology recovered fully. No patient with crescents in 50% or more of glomeruli went on to full recovery. Recurrence of non-renal symptoms did not correlate with outcome. Nephrotic syndrome, decreased GFR, and more severe histopathology at onset, as well as persistence of urinary abnormalities for several years, are ominous signs.", "A prospective study was performed to verify whether early administration of prednisone could be useful in preventing the development of nephropathy in anaphylactoid purpura. Only patients without signs of nephropathy upon initial presentation entered into the study. A total of 84 patients received delta-prednisone (1 mg/kg per day per os for 2 weeks), and 84 patients did not receive steroids. The patients were followed for 24-36 months. None of the 84 patients treated with steroids and 10 (11.9%) of the 84 control patients developed nephropathy 2-6 weeks after the acute episode. In 2 other patients of the untreated group, signs of renal involvement appeared 2 and 6 years after the acute episode respectively. The difference in the prevalence of nephropathy between the two groups is highly significant (P less than 0.001).", "nan" ]