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[ "8942885", "14623704", "16243127", "17668530", "10365928", "19551353", "19588640", "16706244", "6446314", "2953312", "2945705", "6222756", "18289334", "17367893", "9466083", "18705632", "11606923", "9645635", "12789172", "12001006", "7880791", "18561584", "58258", "6219689", "15019322", "3063043", "1356459", "3541803", "11049707", "1524917", "380736", "3890436", "16047874", "10598760", "16378561", "6735625", "9114186", "1590682", "9132982", "1677063", "10476745", "3287815", "18374301" ]

[ "The efficacy of topical metronidazole in the treatment of ocular rosacea.", "A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized 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.", "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.", "A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea.", "Efficacy of topical cyclosporine for the treatment of ocular 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.", "Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea.", "A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea.", "Topical metronidazole therapy for rosacea.", "Topical metronidazole in the treatment of rosacea.", "A double-blind study of I% metronidazole cream versus systemic oxytetracycline therapy for rosacea.", "Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial.", "Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea.", "A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea.", "Comparative study of some treatment modalities of rosacea.", "Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea.", "Topical metronidazole maintains remissions 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 metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea.", "Placebo controlled trial of fusidic acid gel and oxytetracycline for recurrent blepharitis and rosacea.", "Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea.", "Treatment of rosacea by metronidazole.", "Treatment of rosacea with i% metronidazole cream. A double-blind study.", "A randomized trial of topical cyclosporin 0.05% in topical steroid-resistant atopic keratoconjunctivitis.", "Failure of topically applied antibiotics, added to systemic prophylaxis, to reduce perineal wound infection in abdominoperineal excision of the rectum.", "Fosfomycin/metronidazole compared with doxycycline/metronidazole for the prophylaxis of infection after elective colorectal surgery. A randomised double-blind multicentre trial in 517 patients.", "Single-dose chemoprophylaxis in elective colorectal surgery. A comparison between doxycycline plus metronidazole and doxycycline.", "A prospective, randomized, double-blind studyof single high dose versus multiple standard dose gentamicin both in combination withmetronidazole for colorectal surgicalprophylaxis.", "A double-blind study of the efficacy of metronidazole gel in the treatment of malodorous fungating tumours.", "A double-blind trial of a single intravenous dose of metronidazole as prophylaxis against wound infection following appendicectomy.", "Single-dose intravenous metronidazole v. doxycycline prophylaxis in colorectal surgery. An open prospective, randomized trial.", "Combination sodium sulfacetamide 10% and sulfur 5% cream with sunscreens versus metronidazole 0.75% cream for rosacea.", "Double-blind comparison of azelaic acid 20% cream and its vehicle in treatment of papulo-pustular rosacea.", "The treatment of acute infectious conjunctivitis with fusidic acid: a randomised controlled trial.", "Systemic prophylaxis with gentamicin-metronidazole in appendicectomy and colorectal surgery: a prospective controlled clinical study.", "A comparison of oral azithromycin with topical oxytetracycline/polymyxin for the treatment of trachoma in children.", "Multicenter prospective randomized trial comparing ceftazidime plus co-trimoxazole with chloramphenicol plus doxycycline and co-trimoxazole for treatment of severe melioidosis.", "Multicenter comparison of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine hydrochloride, and allantoin in the treatment of symptomatic trichomoniasis.", "Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis.", "A comparison of chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline with doxycycline alone as maintenance therapy for melioidosis.", "Failure of single-dose metronidazole prophylaxis in colorectal surgery. No benefit from high dosage or combination with nalidixic acid.", "Clinical cure of bacterial conjunctivitis with azithromycin 1%: vehicle-controlled, double-masked clinical trial." ]

[ "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.", "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).", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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 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 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.", "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.", "A prospective, randomised, double blind, partial crossover, placebo controlled trial has been conducted to compare the performance of topical fusidic acid gel (Fucithalmic) and oral oxytetracycline as treatment for symptomatic chronic blepharitis. Treatment success was judged both by a reduction in symptoms and clinical examination before and after therapy. Seventy five per cent of patients with blepharitis and associated rosacea were symptomatically improved by fusidic acid gel and 50% by oxytetracycline, but fewer (35%) appeared to benefit from the combination. Patients with chronic blepharitis of other aetiologies did not respond to fusidic acid gel but 25% did benefit from oxytetracycline and 30% from the combination. Our results demonstrate the need to investigate patients with blepharitis for concomitant rosacea as they respond well to targeted therapy.", "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.", "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.", "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.", "To evaluate the short-term efficacy and safety of topical cyclosporin A 0.05% in the treatment of patients with severe, steroid-resistant atopic keratoconjunctivitis (AKC).\n Multicenter, placebo-controlled, double-masked, randomized trial.\n Twenty-two patients with AKC refractory to topical steroid treatment.\n Patients were randomly assigned (1:1) to treatment with topical 0.05% cyclosporin A eyedrops or a placebo (artificial tears) for a period of 28 days, 6 times daily during the first 2 weeks and 4 times daily during the last 2 weeks.\n Symptoms (itching, tearing, discomfort, mucous discharge, and photophobia) and signs (bulbar conjunctival hyperemia, upper tarsal conjunctival papillae, punctate keratitis, corneal neovascularization, cicatrizing conjunctivitis, and blepharitis) of AKC recorded on the day of enrollment and at the end of the treatment period.\n A composite score computed by summing the severity grade over all 5 symptoms and 6 signs of AKC for each patient indicated a greater improvement in the cyclosporin A group relative to the placebo at the end of the 4-week treatment period (P = 0.048 and P = 0.002, for symptoms and signs, respectively). No adverse effects of the treatment with cyclosporin A 0.05% eyedrops were observed.\n Topical cyclosporin A 0.05% seems to be safe and have some effect in alleviating signs and symptoms of severe AKC refractory to topical steroid treatment.", "In a prospective, randomized trial, prophylactic use of topical antibiotics in addition to systemic prophylaxis was studied in patients undergoing abdominoperineal amputation of the rectum. All patients received gentamicin 80 mg and metronidazole 500 mg intravenously at induction of anesthesia, followed by the same dose 8 hourly for 48 hours. In accordance with the randomization, half of the patients were additionally given gentamicin 160 mg + metronidazole 400 mg topically into the perineal wound at closure. Perineal wound infection appeared in 19 of the 41 patients who received both systemic and topical prophylaxis, and in 18 of the 38 with only systemic antibiotics. Cell-mediated immunity was preoperatively assessed with a skin test (Multitest) in all but three patients. Impairment of cell-mediated immunity was associated with significantly heightened rate of wound infection, and these patients did not benefit from topical antibiotics.", "To find out if fosfomycin together with metronidazole was any better than doxycycline with metronidazole for the prophylaxis of infection before elective colorectal operations.\n Multicentre, double blind, random control trial.\n Nine Swedish hospitals. SUBJECTS-559 patients admitted for elective colorectal operations.\n Fosfomycin 8 g and metronidazole 1 g before operation and fosfomycin 8 g eight hours afterwards, or doxycycline 400 mg and metronidazole 1 g before operation, and placebo eight hours afterwards.\n Incidence of all types of infection, mortality, and side effects.\n There were no significant differences between the groups for any of the outcome measures studied, the overall abdominal infection rates (wound, deep, and septicaemia) being 4.6% and 7.4%, and the remote infection rates (pneumonia, urinary tract, and central venous line) 15.1% and 12.8%, respectively. Of the predictors studied, only duration of operation was significantly related to risk of infection.\n The combination of fosfomycin and metronidazole was as safe and effective as that of doxycycline and metronidazole in preventing infections after elective colorectal operations.", "In a prospective, randomized double-blind study either 400 mg of doxycycline + 1500 mg of metronidazole (D + M) or 400 mg of doxycycline (D) alone were given intravenously as a single preoperative dose to patients admitted for elective colorectal surgery. A comparison of the rate of postoperative septic complications was made. After excluding drop-out patients, 261 patients remained for evaluation. In 135 patients with D + M treatment there were four postoperative septic complications (3.0%). In 126 patients with D treatment 20 septic complications related to the surgical procedure occurred (15.9%). The difference is highly significant (p less than 0.005). Most postoperative infections were superficial wound infections (14 of 24 patients), and the mean hospital stay in the two treatment groups was equal. Bacteriologic studies showed a highly significant reduction in anaerobes in cultures from perioperative intra-abdominal fluid in the D + M treatment group. The study has thus showed that the addition of metronidazole, an efficient agent against anaerobic bacteria, to an antimicrobial agent against aerobic bacteria significantly reduces postoperative septic complications in elective colorectal surgery.", "Single, high dose regimens of gentamicin plus metronidazole for colorectal surgical prophylaxis have not been adequately studied. Patients received single high dose gentamicin (4.5 mg/kg) plus metroni-dazole (500 mg) preoperatively or multiple standard dose gentamicin (1.5 mg/kg) plus metronidazole (500 mg) preoperatively and every 8h for 24h postoperatively. The deep surgical site infection (SSI) rates were 8.1% (6/74) and 6.9% (5/72) in the single high dose and multiple standard dose groups, respectively (P= 0.94). There was a trend towards fewer superficial SSIs in the single high dose group with infection rates of 18.9% (14/74) vs. 30.6% (22/72) (P= 0.05). Diabetes mellitus (odds ratio = 7.04) and surgery duration of longer than 3h (odds ratio = 5.46) were independent risk factors for the development of SSIs. A subset analysis of prolonged operations found significantly fewer superficial SSIs in the single high dose group than in the multiple standard dose group with rates of 22.2% (6/27) vs. 55% (11/20), respectively (P= 0.021). Single high dose gentamicin plus metronidazole preoperatively was at least as effective as the multiple standard dose regimen and may be more effective for prolonged operations.\n Copyright 2000 The Hospital Infection Society.", "A double-blind placebo-controlled trial was undertaken to assess the value of topical metronidazole gel preparation in the palliation of the offensive odour of fungating tumours. This 5 day trial was followed by a 6 day period during which all patients received the active gel. Subjective odour assessments were performed by both patients and medical staff. 11 patients were entered and the randomisation was then halted because of an obvious overall benefit over the whole 11 days. There was a non-significant trend in favour of the active treatment during the initial double-blind placebo-controlled phase of the trial, and no side-effects were observed.", "One hundred patients undergoing appendicectomy through a right iliac fossa incision were randomized to receive normal saline or 500 mg metronidazole as an intravenous infusion during the operation. One patient in the saline group developed an erythematous rash. There were 13 wound infections (as defined by the discharge of pus), 12 (out of 51) in the saline group and 1 (out of 49) in the metronidazole group. Bacteroides spp. were frequently cultured from the lumen of removed appendices and from pus obtained from infected wounds. This work supports the value of metronidazole but suggests that a single-dose regimen is adequate for prophylaxis.", "In an open prospective, randomized study of antimicrobial prophylaxis in colorectal surgery, using a single intravenous dose, metronidazole (1 g) was more effective than doxycycline (0.2 g). The difference in infection rates (2/41 = 5% v. 7/33 = 21%) was statistically significant. Prolonged administration of either agent (2-7 days) yielded results comparable to those with single doses. Five emergency cases were admitted to the study. In two of them, a metronidazole-based therapeutic regimen prevented postoperative infection, whereas infection occurred in all 3 patients given doxycycline therapy. The total infection rate after elective surgery was 4% with metronidazole and 25% with doxycycline prophylaxis. The infections in the metronidazole group were superficial and caused by Escherichia coli, whereas half of the infections in the doxycycline group were intra-abdominal and due to intestinal aerobic and/or anaerobic bacteria. In contrast to doxycycline, therefore, metronidazole prevented postoperative anaerobic infection and was associated with low incidence of aerobic infection.", "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.", "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.", "Acute infectious conjunctivitis is a common disorder in primary care. Despite a lack of evidence regarding the effectiveness of topical antibiotics for the treatment of acute infectious conjunctivitis, most patients presenting in primary care with the condition receive topical antibiotics. In The Netherlands, fusidic acid is most frequently prescribed.\n To assess the effectiveness of fusidic acid gel compared to placebo for acute infectious conjunctivitis.\n Double-blind randomised placebo-controlled trial.\n Twenty-five Dutch primary care centres.\n Adults presenting with a red eye and either (muco)purulent discharge or glued eyelid(s) were allocated to either one drop of fusidic acid gel 1% or placebo, four times daily during one week. The main outcome measure was the difference in recovery rates at 7 days. Secondary outcome measures were difference in bacterial eradication rates, a survival time analysis of the duration of symptoms, and the difference in recovery rates in culture-positive and culture-negative patients.\n One hundred and eighty-one patients were randomised and 163 patients were analysed. Forty-five of the 73 patients in the treatment and 53 of the 90 patients in the placebo group recovered (adjusted risk difference = 5.3% [95% confidence interval {CI} = -11 to 18]). There was no difference between the median duration of symptoms in the two groups. At baseline, the prevalence of a positive bacterial culture was 32% (58/181). The bacterial eradication rate was 76% in the treatment and 41% in the placebo group (risk difference = 35% [95% CI = 9.3 to 60.4]). In culture positive patients, the treatment effect tended to be strong (adjusted risk difference = 23% [95% CI = -6 to 42]).\n At 7 days, cure rates in the fusidic acid gel and placebo group were similar, but the confidence interval was too wide to clearly demonstrate their equivalence. These findings do not support the current prescription practices of fusidic acid by GPs.", "A prospective, randomized, clinical study was carried out in 188 patients undergoing appendicectomy or colorectal surgery to test the efficacy of prophylactic, parenterally-administered antibiotics in the prevention of infection. The results show the effectiveness of the association gentamicin-metronidazole (9.4% of infections), compared to the control group with no antibiotics (39.1% of infections), X2 = 14.1; P less than 0.001).", "Trachoma, an infectious keratoconjunctivitis caused by Chlamydia trachomatis, is a leading cause of preventable blindness in developing countries. In this study we compared oral azithromycin with oxytetracycline/polymyxin eye ointment (once daily for 5 days every 4 weeks; total of six treatment cycles) for the treatment of active endemic trachoma in 168 rural Egyptian children. A suspension of azithromycin was administered to children as a dose of 20 mg/kg by one of three schedules: a single dose, one dose a week for 3 weeks, and one dose every 4 weeks for a total of six doses. The children's clinical status and chlamydial infection rates were evaluated for 1 year. The clinical cure rates were 35% 2 months after initial treatment, 16% at 8 months (during the annual autumn epidemic of purulent conjunctivitis), and 47% at 1 year. The pretreatment chlamydial infection rate of 33% (determined by direct immunofluorescence) decreased to 5% at 2 months and was 9% at 12 months. There were no significant clinical or laboratory differences among the four treatment groups. Thus, 1-6 doses of azithromycin were equivalent to 30 days of topical oxytetracycline/polymyxin ointment and may offer an effective alternative means of controlling endemic trachoma.", "A prospective randomized trial was conducted at Srinagarind and Khon Kaen hospitals. Ceftazidime (100 mg/kg of body weight per day) and co-trimoxazole (trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) therapy was compared with conventional therapy (chloramphenicol, 100 mg/kg/day; doxycycline, 4 mg/kg/day; trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) in the treatment of 64 patients with bacteriologically confirmed cases of severe melioidosis who were admitted during September 1986 to January 1989. Of 61 evaluable patients (3 were excluded because of severe drug allergies), 42 were septicemic, and 31 of these patients had the most severe form, disseminated septicemic melioidosis. Their cumulative mortalities on day 7 were compared. There were significantly lower overall mortalities from melioidosis, septicemic melioidosis, and disseminated septicemic melioidosis in the group receiving the new treatment compared with those in the group receiving the conventional treatment (47 versus 18.5% [P = 0.039], 57.7 versus 25% [P = 0.039], and 82.3 versus 30.7% [P = 0.006], respectively); but the differences could have been influenced by the greater severity of illness, e.g., shock at initial presentation, in the patients who received the conventional treatment. Among patients with disseminated septicemia and initial shock, there was no significant difference in mortality between the regimens. Both regimens effectively eradicated bacteria from the circulation within 24 h (97 versus 96%, respectively). We recommend ceftazidime and co-trimoxazole as the drugs of choice for treatment of severe melioidosis, especially in those patients with disseminated septicemia.", "Trichomonas vaginalis is a common vaginal pathogen. Oral metronidazole is the drug of choice for the treatment of trichomoniasis. Oral metronidazole, however, may cause unpleasant side effects and is contraindicated during the first trimester of pregnancy. In vitro studies and preliminary clinical data have suggested that intravaginal clotrimazole may be effective against this pathogen.\n To compare the efficacy of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine, and allantoin (AVC suppositories) in the treatment of women with symptomatic trichomoniasis.\n In a multicenter, open-label trial conducted in 1982 and 1983, 168 symptomatic women with microscopically evident vaginal trichomoniasis were randomized to receive any of 2 g of metronidazole as a single oral dose, two 100-mg clotrimazole vaginal tablets once a day for 7 days, or vaginal suppositories containing 1.05 g of sulfanilamide, 14 mg of aminacrine hydrochloride, and 140 mg of allantoin (AVC suppositories) twice a day for 7 days. Wet mounts and cultures were repated at 1 to 2 and 4 to 6 weeks after completion of treatment.\n The number of patients who had positive cultures after treatment were 40/45 (88.9%) in the clotrimazole group, 35/43 (81.4%) in the AVC suppository group, and 9/45 (20%) in the metronidazole group (P < 0.001). All treatments were associated with a reduction in reported symptoms. Oral metrohidazole was more effective in reducing symptoms than either of the topical preparations. Adverse events, mostly mild or moderate in severity, were reported by 7 (14.6%) of 48 patients who had received oral metronidazole and 4 (7.8%) of 51 women who used AVC suppositories. There were no adverse events reported by the 50 women who used clotrimazole vaginal tablets.\n Oral metronidazole was more effective in eradicating T. vaginalis than clotrimazole vaginal tablets or AVC vaginal suppositories. All three regimens reduced symptoms; oral metronidazole was more effective in reducing symptoms than either topical preparation.", "A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.", "A prospective, open, randomized, comparative treatment trial was conducted to compare the therapeutic efficacy of the conventional four-drug combination (chloramphenicol, trimethoprim-sulfamethoxazole, and doxycycline) with that of doxycycline alone in oral maintenance treatment of melioidosis. Adult Thai patients with culture-confirmed melioidosis were randomized to receive treatment with either regimen for a minimum of 12 weeks, usually following intravenous treatment of severe disease. The main outcome measure was culture-confirmed relapse. One hundred sixteen patients were enrolled; 109 had culture-confirmed melioidosis, and 87 were considered evaluable (43 had received doxycycline). Culture-confirmed relapse occurred in one patient randomized to the conventional regimen and in 11 (25.6%) randomized to the doxycycline regimen (P = .009), and treatment failed for 8 (18.2%) versus 20 (46.5%), respectively (P = .009). Adverse effects occurred in 26% of patients overall. Doxycycline alone cannot be recommended for a first-line regimen of oral maintenance treatment of melioidosis.", "In an open prospective study of postoperative infectious complications, patients undergoing elective colorectal surgery were randomly allocated to one of three groups receiving parenteral single-dose antimicrobial prophylaxis (1 g or 3 g metronidazole or 1 g metronidazole + 3 g nalidixic acid). Because of an unacceptably high rate of surgical infection in all three groups (36%, 29% and 39%, p greater than 0.1) among the first 103 evaluable patients, the study was discontinued. Nalidixic acid--though effective in in vitro tests of bacterial susceptibility--thus was found to be of little or no value as prophylaxis against Gram-negative infection. As the observed infection rate when metronidazole was given at the start of operation was seven-fold that previously found in the same department when 1 g metronidazole was administered 3-4 hours preoperatively (28/103 vs. 2/50, p less than 0.01), the timing of metronidazole prophylaxis was assumed to be potentially important for its ability to protect also against aerobic postoperative infection.", "To analyze the effect of azithromycin 1% ophthalmic solution in DuraSite (InSite Vision, Inc, Alameda, California, USA) on bacterial conjunctivitis.\n Prospective, randomized, vehicle-controlled, parallel-group, double-masked multicenter clinical study.\n Eligible male or female participants with a clinical diagnosis of acute bacterial conjunctivitis were randomized to either 1% azithromycin in DuraSite or vehicle for five days. Infected eyes were dosed twice daily on days 1 and 2 and once daily on days 3 through 5. Conjunctival cultures were obtained at baseline, visit 2 (day 3 or 4), and visit 3 (day 6 or 7). The primary end point was clinical resolution of signs and symptoms (rating of zero on ocular discharge, bulbar and palpebral injection) at visit 3. Efficacy measures were clinical resolution and bacterial eradication as evaluated in the per-protocol population. Safety was assessed by adverse events, slit-lamp findings, and ophthalmoscopy.\n Two hundred and seventy-nine participants (n = 130, 1% azithromycin in DuraSite; n = 149, vehicle), age one to 96 years, were evaluated for efficacy. Clinical resolution with azithromycin ophthalmic solution was statistically significant compared with that of vehicle (P = .030) at visit 3. Bacterial eradication rates with azithromycin ophthalmic solution reached 88.5% at visit 3 (P < .001) and included some pathogens resistant to azithromycin in vitro. Overall, adverse event rates were similar in both treatment groups.\n Azithromycin 1% ophthalmic solution in DuraSite showed statistically significant differences in clinical resolution and bacterial eradication rates when compared with vehicle. Because it was well tolerated in this population, it may be a viable treatment option for children and adults with bacterial conjunctivitis." ]

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[ "Efficacy of a single computer-tailored e-mail for smoking cessation: results after 6 months.", "Web-based smoking-cessation programs: results of a randomized trial.", "Comparing internet assistance for smoking cessation: 13-month follow-up of a six-arm randomized controlled trial.", "Using the internet to assist smoking prevention and cessation in schools: a randomized, controlled trial.", "Design and pilot evaluation of an internet smoking cessation program.", "Comparing two web-based smoking cessation programs: randomized controlled trial.", "Efficacy of an internet program for smoking cessation during and after inpatient rehabilitation treatment: a quasi-randomized controlled trial.", "Computer-tailored smoking cessation intervention in a general population setting in Germany: outcome of a randomized controlled trial.", "Long-term effectiveness of computer-generated tailored feedback in smoking cessation.", "A randomized controlled trial of multiple tailored messages for smoking cessation among callers to the cancer information service.", "Toward evidence-based Internet interventions: A Spanish/English Web site for international smoking cessation trials.", "Evaluation of a Dutch community-based smoking cessation intervention.", "Randomized controlled trial of a computer-based, tailored intervention to increase smoking cessation counseling by primary care physicians.", "A theory-based video messaging mobile phone intervention for smoking cessation: randomized controlled trial.", "The effectiveness of personally tailored computer-generated advice letters for smoking cessation.", "A randomised control study of a fully automated internet based smoking cessation programme.", "Web-based support as an adjunct to group-based smoking cessation for adolescents.", "The effectiveness of personalized smoking cessation strategies for callers to a Quitline service.", "Evaluation of an Internet virtual world chat room for adolescent smoking cessation.", "Happy ending: a randomized controlled trial of a digital multi-media smoking cessation intervention." ]

[ "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.", "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.", "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.", "To evaluate the impact of a classroom-based, Web-assisted tobacco intervention addressing smoking prevention and cessation with adolescents.\n A two-group randomized control trial with 1,402 male and female students in grades 9 through 11 from 14 secondary schools in Toronto, Canada. Participants were randomly assigned to a tailored Web-assisted tobacco intervention or an interactive control condition task conducted during a single classroom session with e-mail follow-up. The cornerstone of the intervention was a five-stage interactive Web site called the Smoking Zine (http://www.smokingzine.org) integrated into a program that included a paper-based journal, a small group form of motivational interviewing, and tailored e-mails.\n Resistance to smoking, behavioral intentions to smoke, and cigarette use were assessed at baseline, postintervention, and three- and six-month follow-up. Multilevel logistic growth modeling was used to assess the effect of the intervention on change over time.\n The integrated Smoking Zine program helped smokers significantly reduce the likelihood of having high intentions to smoke and increased their likelihood of high resistance to continued cigarette use at 6 months. The intervention also significantly reduced the likelihood of heavy cigarette use adoption by nonsmokers during the study period.\n The Smoking Zine intervention provided cessation motivation for smokers most resistant to quitting at baseline and prevented nonsmoking adolescents from becoming heavy smokers at 6 months. By providing an accessible and attractive method of engaging young people in smoking prevention and cessation, this interactive and integrated program provides a novel vehicle for school- and population-level health promotion.", "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.", "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 test the feasibility and efficacy of an internet program for smoking cessation during and after inpatient treatment in rehabilitation centers.\n A total of 7574 consecutively admitted inpatients from three German rehabilitation centers were assessed for smoking status. Daily smokers or former daily smokers who regularly used the internet and e-mail were proactively invited for study participation. Out of 749 eligible patients, 477 (64%) participated in the study and were randomly assigned to an intervention or an assessment only control group based on the calendar week of admission. Patients of the intervention group had the possibility to use an internet program for smoking cessation for a period of six months. The program provided at least one but up to seven individual counseling sessions through a computer expert system, informational websites and a message board.\n At six-months follow-up, seven-day point prevalence smoking abstinence was twice as high in the intervention group as in the control group (OR=2.0; CI 1.1-3.8; p=.02).\n Proactive recruitment of smokers in combination with the provision of an internet program for smoking cessation allow for an inexpensive and effective smoking cessation support during and after inpatient rehabilitation treatment.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "This study reports the outcome of a randomized controlled trial testing a computer-tailored smoking cessation intervention based on the transtheoretical model in a general population setting in Germany. Participants of the smoking intervention study were recruited from an existing general population health examination survey in a university hospital. The sample consisted of 611 current and former smokers at baseline, and of 485 participants in the core group of baseline daily cigarette smokers. Follow-ups were conducted 6, 12, 18, and 24 months after baseline. The intervention was designed for both current and former smokers, involved up to three individualized feedback letters, and was created using expert-system technology. Based on 7-day point-prevalence abstinence and 6-month prolonged abstinence as the outcome measures, the study identified no significant differences between the intervention and control groups. Modeling the full longitudinal data in generalized estimation equation analyses, using different nonresponse procedures, and adjusting for covariates did not alter the results. We conclude that the computer-tailored transtheoretical model-based smoking cessation intervention, as delivered in this study and in this special setting, was ineffective.", "Although tailored interventions consisting of only a few pages of information lead to more quitting than no intervention in the short term, the long-term efficacy of a single tailored intervention still has to be proven. In the present study smokers were reactively recruited and randomly allocated to one of four intervention conditions: (1) outcome information, (2) self-efficacy enhancing information, (3) both sorts of information or (4) no information. Smokers in the three experimental groups received computer-generated tailored feedback containing the condition-specific information, by mail. The results from the 14 months follow-up can be summarized as follows. Compared to the no information condition, all three experimental conditions led to significantly more smokers who had engaged in 24-h quit attempts. However, no experimental condition led to more 7-day quitting than the no information condition. With regard to continuous abstinence, the experimental condition offering a combination of outcome information and self-efficacy enhancing information had a significant effect, compared to the no information condition. It is concluded that a minimal six-page tailored intervention can be beneficial in supporting smokers to quit smoking, even after 14 months.", "Self-help materials computer-tailored to the specific needs of smokers have shown promise as a high-reach, low-cost intervention for smoking cessation. Adding tailored cessation materials to telephone-based cessation counseling may be a way of generating greater efficacy in promoting and maintaining cessation. The objective of this study is to assess the efficacy of adding different types of behavioral smoking cessation materials to brief telephone-based cessation counseling.A total of 1,978 smokers calling the National Cancer Institute's (NCI's) Cancer Information Service (CIS) for help in quitting smoking initially received brief cognitive-behavioral cessation counseling from a CIS information specialist. Following a baseline interview administered by the information specialist, subjects were randomly assigned to one of four conditions, each delivered by U.S. mail: a single, untailored smoking cessation guide (SU); a single, tailored smoking cessation guide (ST); a series of four (multiple) printed materials tailored only to baseline data (MT); and a series of four (multiple) printed materials tailored to baseline as well as retailored using 5-month interim progress data (MRT). The primary outcome measure was 7-day point prevalence abstinence rates assessed using a computer-assisted telephone interview (CATI) at 12-month follow-up.At 12-month follow-up, using intent-to-treat, imputed, and per-protocol analyses, no differences were found among the four experimental conditions (linear trend), or when the ST, MT, and MRT groups were compared with the control (SU) group. Participants in the two multiple message group conditions combined (MT + MRT), however, had significantly higher abstinence rates than participants in the two single message group conditions combined (SU + ST). Moreover, among subjects who reported quitting at the 5-month follow-up, participants receiving the MRT materials reported higher abstinence rates at 12 months than the other three groups combined (SU + ST + MT). The results of this study support the effectiveness, over and above a single telecounseling interaction, of multiple tailored print material contacts on cessation. These effects, however may be due to tailoring, or the longitudinal nature of the two multiple tailored conditions, or both. The strongest evidence for tailoring occurred in the MRT condition for relapse prevention, suggesting that print materials tailored to interim progress may be especially effective in this context. The qualities of specific psychosocial and communication elements in tailored materials should receive attention in future research.", "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.", "Until 1990, smoking cessation interventions in the Netherlands were limited. The utility and effectiveness of community-based smoking cessation programs have not been examined.\n In a treatment city (Den Bosch) a multicomponent community-based smoking cessation intervention was implemented in which local mass media and general practitioners draw smokers' attention to a local quit line. Telephone counselors advised applicants on their choice between self-help and group treatment and optional telephone counseling. Another Dutch city (Apeldoorn) served as a control. Population samples of smokers (n = 547 and n = 546) were interviewed three times at approximately 7-month intervals. Self-help manual requesters (n = 84) and group participants (n = 83) were interviewed before and 6 months after treatment.\n Treatment modalities were successful; 13% of self-help manual requesters and 22% of group participants were abstinent after 6 months. On a population level the intervention resulted in significantly higher recall of self-help manual and group program in the treatment city. A modest intervention effect on prevalence of abstinence was found at the community level.\n Treatment modalities were effective within their participants, but the intervention effectiveness on a community level was limited. No significant difference was found between quit rates after 14 months (7% in treatment city and 9% in control city). Several system failures could be identified. However, probably the intervention effect was seriously confounded by two national governmental publicity campaigns introducing and reinforcing a mandatory smoking ban and a series of national campaigns initiated by the united Dutch tobacco producers opposing the ban.", "The primary care visit represents an important venue for intervening with a large population of smokers. However, physician adherence to the Smoking Cessation Clinical Guideline (5As) remains low. We evaluated the effectiveness of a computer-tailored intervention designed to increase smoking cessation counseling by primary care physicians.\n Physicians and their patients were randomized to either intervention or control conditions. In addition to brief smoking cessation training, intervention physicians and patients received a one-page report that characterized the patients' smoking habit and history and offered tailored recommendations. Physician performance of the 5As was assessed via patient exit interviews. Quit rates and smoking behaviors were assessed 6 months postintervention via patient phone interviews. Intervention effects were tested in a sample of 70 physicians and 518 of their patients. Results were analyzed via generalized and mixed linear modeling controlling for clustering.\n Intervention physicians exceeded controls on \"Assess\" (OR 5.06; 95% CI 3.22, 7.95), \"Advise\" (OR 2.79; 95% CI 1.70, 4.59), \"Assist-set goals\" (OR 4.31; 95% CI 2.59, 7.16), \"Assist-provide written materials\" (OR 5.14; 95% CI 2.60, 10.14), \"Assist-provide referral\" (OR 6.48; 95% CI 3.11, 13.49), \"Assist-discuss medication\" (OR 4.72;95% CI 2.90, 7.68), and \"Arrange\" (OR 8.14; 95% CI 3.98, 16.68), all p values being < 0.0001. Intervention patients were 1.77 (CI 0.94, 3.34,p = 0.078) times more likely than controls to be abstinent (12 versus 8%), a difference that approached, but did not reach statistical significance, and surpassed controls on number of days quit (18.4 versus 12.2, p < .05) but not on number of quit attempts.\n The use of a brief computer-tailored report improved physicians' implementation of the 5As and had a modest effect on patients' smoking behaviors 6 months postintervention.", "Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones. This social cognitive theory-based intervention (called \"STUB IT\") used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques.\n The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation.\n A randomized controlled trial was conducted with 6-month follow-up. Participants had to be 16 years of age or over, be current daily smokers, be ready to quit, and have a video message-capable phone. Recruitment targeted younger adults predominantly through radio and online advertising. Registration and data collection were completed online, prompted by text messages. The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date, role model, and timing of messages. Extra messages were available on demand to beat cravings and address lapses. The control group also set a quit date and received a general health video message sent to their phone every 2 weeks.\n The target sample size was not achieved due to difficulty recruiting young adult quitters. Of the 226 randomized participants, 47% (107/226) were female and 24% (54/226) were Maori (indigenous population of New Zealand). Their mean age was 27 years (SD 8.7), and there was a high level of nicotine addiction. Continuous abstinence at 6 months was 26.4% (29/110) in the intervention group and 27.6% (32/116) in the control group (P = .8). Feedback from participants indicated that the support provided by the video role models was important and appreciated.\n This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone. However, there was sufficient positive feedback about the ease of use of this novel intervention, and the support obtained by observing the role model video messages, to warrant further investigation.\n Australian New Zealand Clinical Trials Registry Number: ACTRN12606000476538; http://www.anzctr.org.au/trial_view.aspx?ID=81688 (Archived by WebCite at http://www.webcitation.org/5umMU4sZi).", "To assess the effectiveness of a new computer-generated tailored advice programme designed to be used by smokers and recent quitters having problems staying stopped.\n Randomized trial comparing a series of questionnaire assessments leading to tailored computer-generated advice letters mailed at strategically relevant times, to a no extra treatment control sent standardized printed self-help materials.\n Victoria, Australia.\n A total of 1058 smokers or recent quitters recruited from callers to the Quitline.\n Smoking status and sustained abstinence at 12-month follow-up, plus extent of participation in the intervention.\n Using a conservative analysis (missing data coded as a treatment failure), 6-month sustained abstinence was reported by significantly more participants in the computer-generated tailored advice (20%) than the standard printed materials condition (12%) at 12-month follow-up OR 1.82 (1.31-2.55)). Group differences in point prevalence abstinence (28% intervention, 25% control) were not significant. Among participants in the tailored advice condition, 6-month sustained abstinence was associated with the number of advice letters received.\n The provision of a series of tailored, computer-generated advice letters resulted in greater rates of sustained cessation than for controls. A dose-response relationship was found, with increased compliance with the intervention associated with improved cessation outcomes. The programme appears to have much of its effect by preventing relapse.", "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.", "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 assess the effectiveness of a program of computer-generated tailored advice for callers to a telephone helpline, and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation.\n Randomized controlled trial comparing: (1) untailored self-help materials; (2) computer-generated tailored advice only, and (3) computer-generated tailored advice plus callback telephone counselling. Assessment surveys were conducted at baseline, 3, 6 and 12 months.\n Victoria, Australia.\n A total of 1578 smokers who called the Quitline service and agreed to participate.\n Smoking status at follow-up; duration of cessation, if quit; use of nicotine replacement therapy; and extent of participation in the callback service.\n At the 3-month follow-up, significantly more (chi2(2) = 16.9; P < 0.001) participants in the computer-generated tailored advice plus telephone counselling condition were not smoking (21%) than in either the computer-generated advice only (12%) or the control condition (12%). Proportions reporting not smoking at the 12-month follow-up were 26%, 23% and 22%, respectively (NS) for point prevalence, and for 9 months sustained abstinence; 8.2, 6.0, and 5.0 (NS). In the telephone counselling group, those receiving callbacks were more likely than those who did not to have sustained abstinence at 12 months (10.2 compared with 4.0, P < 0.05). Logistic regression on 3-month data showed significant independent effects on cessation of telephone counselling and use of NRT, but not of computer-generated tailored advice.\n Computer-generated tailored advice did not enhance telephone counselling, nor have any independent effect on cessation. This may be due to poor timing of the computer-generated tailored advice and poor integration of the two modes of advice.", "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.", "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." ]

[ "17556431", "16113617", "19968378", "17984403", "9366660", "17581445", "15169696" ]

[ "Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial.", "A randomized effectiveness trial of brief cognitive-behavioral therapy for depressed adolescents receiving antidepressant medication.", "Randomized controlled trial of a family cognitive-behavioral preventive intervention for children of depressed parents.", "A randomized controlled trial of fluoxetine and cognitive behavioral therapy in adolescents with major depression, behavior problems, and substance use disorders.", "A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression.", "A pilot randomized controlled trial of combined trauma-focused CBT and sertraline for childhood PTSD symptoms.", "A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents." ]

[ "To determine whether a combination of a selective serotonin reuptake inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical care is more effective in the short term than an SSRI and clinical care alone in adolescents with moderate to severe major depression.\n Pragmatic randomised controlled superiority trial.\n 6 outpatient clinics in Manchester and Cambridge.\n 208 adolescents, aged 11-17, with moderate to severe major or probable major depression who had not responded to a brief initial intervention. Adolescents with suicidality, depressive psychosis, or conduct disorder were included.\n 103 adolescents received an SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial lasted 12 weeks, followed by a 16 week maintenance phase.\n Change in score on the Health of the Nation outcome scales for children and adolescents (primary outcome) from baseline with 12 weeks as the primary and 28 weeks as the follow-up end point. Secondary measures were change in scores on the mood and feelings questionnaire, the revised children's depression rating scale, the children's global assessment scale, and the clinical global impression improvement scale.\n At 12 weeks the treatment effect for the primary outcome was -0.64 (95% confidence interval -2.54 to 1.26, P=0.50). In a longitudinal analysis, there was no difference in effectiveness of treatment for the primary (average treatment effect 0.001, -1.52 to 1.52, P=0.99) or secondary outcome measures. On average there was a decrease in suicidal thoughts and self harm. There was no evidence of a protective effect of cognitive behaviour therapy on suicidal thinking or action. By 28 weeks, 57% were much or very much improved with 20% remaining unimproved.\n For adolescents with moderate to severe major depression there is no evidence that the combination of CBT plus an SSRI in the presence of routine clinical care contributes to an improved outcome by 28 weeks compared with the provision of routine clinical care plus an SSRI alone.\n Current Controlled Trials ISRCNT 83809224.", "To test a collaborative-care, cognitive-behavioral therapy (CBT) program adjunctive to selective serotonin reuptake inhibitor (SSRI) treatment in HMO pediatric primary care.\n A randomized effectiveness trial comparing a treatment-as-usual (TAU) control condition consisting primarily of SSRI medication delivered outside the experimental protocol (n = 75) versus TAU SSRI plus brief CBT (n = 77). Participants were identified by a recent dispense of SSRI medication followed by telephone screening. Adolescents with a diagnosis of major depressive disorder (n = 152) were enrolled. The CBT program employed cognitive restructuring and/or behavioral activation training. Therapists consulted with prescribing pediatricians to improve medication adherence.\n Through 1-year follow-up, the authors found CBT advantages on the Short Form-12 Mental Component Scale (p = .04), reductions in TAU outpatient visits (p = .02), and days' supply of all medications (p = .01). No effects were detected for major depressive disorder episodes; a nonsignificant trend favoring CBT was detected on the Center for Epidemiology Depression Scale (p = .07).\n The authors detected a weak CBT effect, possibly rendered less significant by the small sample and likely attenuated by the unexpected reduction in SSRI pharmacotherapy in the CBT condition. Small, incremental improvements over monotherapy, such as observed in this study, most likely represent the new norm in adolescent depression treatment research.", "A family cognitive-behavioral preventive intervention for parents with a history of depression and their 9-15-year-old children was compared with a self-study written information condition in a randomized clinical trial (n = 111 families). Outcomes were assessed at postintervention (2 months), after completion of 4 monthly booster sessions (6 months), and at 12-month follow-up. Children were assessed by child reports on depressive symptoms, internalizing problems, and externalizing problems; by parent reports on internalizing and externalizing problems; and by child and parent reports on a standardized diagnostic interview. Parent depressive symptoms and parent episodes of major depression also were assessed. Evidence emerged for significant differences favoring the family group intervention on both child and parent outcomes; strongest effects for child outcomes were found at the 12-month assessment with medium effect sizes on most measures. Implications for the prevention of adverse outcomes in children of depressed parents are highlighted.", "To evaluate the effect of fluoxetine hydrochloride vs placebo on major depressive disorder, substance use disorder (SUD), and conduct disorder (CD) in adolescents receiving cognitive behavioral therapy (CBT) for SUD.\n Randomized controlled trial.\n A single-site study conducted between May 2001 and August 2004.\n One hundred twenty-six adolescents aged 13 to 19 years recruited from the community and meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic criteria for current major depressive disorder, lifetime CD, and at least 1 nontobacco SUD.\n Sixteen weeks of fluoxetine hydrochloride, 20 mg/d, or placebo, with CBT.\n For depression, Childhood Depression Rating Scale-Revised and Clinical Global Impression Improvement; for SUD, self-reported nontobacco substance use and urine substance use screen results in the past 30 days; and for CD, self-reported symptoms in the past 30 days.\n Fluoxetine combined with CBT had greater efficacy than did placebo and CBT according to changes on the Childhood Depression Rating Scale-Revised (effect size, 0.78) but not on the Clinical Global Impression Improvement treatment response (76% and 67%, respectively; relative risk, 1.08). There was an overall decrease in self-reported substance use (4.31 days; 95% confidence interval, 2.12-6.50) and CD symptoms (relative risk, 1.20; 95% confidence interval, 0.82-1.59), but neither difference between groups was statistically significant. The proportion of substance-free weekly urine screen results was higher in the placebo-CBT group than in the fluoxetine-CBT group (mean difference, 2.10; 95% confidence interval, 0.37-4.15).\n Fluoxetine and CBT had greater efficacy than did placebo and CBT on one but not both depression measures and was not associated with greater decline in self-reported substance use or CD symptoms. The CBT may have contributed to higher-than-expected treatment response and mixed efficacy findings, despite its focus on SUD.", "Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blind trials of antidepressants (largely tricyclic agents) have yet to reveal that any antidepressant is more effective than placebo. This article is of a randomized, double-blind, placebo-controlled trial of fluoxetine in children and adolescents with depression.\n Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic major depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks. Randomization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks, followed 1 week later by a 1-week, single-blind placebo run-in. Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children's Depression Rating Scale--Revised, a measure of the severity depressive symptoms.\n Of the 96 patients, 48 were randomized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) receiving placebo were rated \"much\" or \"very much\" improved on the Clinical Global Impressions scale at study exit (chi 2 = 5.1, df = 1, P = .02). Significant differences were also noted in weekly ratings of the Children's Depression Rating Scale--Revised after 5 weeks of treatment (using last observation carried forward). Equivalent response rates were found for patients aged 12 years and younger (n = 48) and those aged 13 years and older (n = 48). However, complete symptom remission (Children's Depression Rating Scale--Revised < or = 28) occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients.\n Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression. Complete remission of symptoms was rare.", "To examine the potential benefits of adding a selective serotonin reuptake inhibitor, sertraline, versus placebo, to trauma-focused cognitive-behavioral therapy (TF-CBT) for improving posttraumatic stress disorder and related psychological symptoms in children who have experienced sexual abuse.\n Twenty-four 10- to 17-year-old female children and adolescents and their primary caretakers were randomly assigned to receive TF-CBT + sertraline or TF-CBT + placebo for 12 weeks.\n Both groups experienced significant improvement in posttraumatic stress disorder and other clinical outcomes from pre- to posttreatment with no significant group x time differences between groups except in Child Global Assessment Scale ratings, which favored the TF-CBT + sertraline group.\n Only minimal evidence suggests a benefit to adding sertraline to TF-CBT. A drawback of adding sertraline was determining whether TF-CBT or sertraline caused clinical improvement for children with comorbid depression. Current evidence therefore supports an initial trial of TF-CBT or other evidence-supported psychotherapy for most children with PTSD symptoms before adding medication.", "Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents. The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression.\n An 8-week, randomized, double-blind, placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children (ages 7-11) and adolescents (ages 12-17) with major depressive disorder. Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Patients (N=174) were treated initially with placebo or 20 mg/day of citalopram, with an option to increase the dose to 40 mg/day at week 4 if clinically indicated. The primary outcome measure was score on the Children's Depression Rating Scale-Revised; the response criterion was defined as a score of < or =28.\n The overall mean citalopram dose was approximately 24 mg/day. Mean Children's Depression Rating Scale-Revised scores decreased significantly more from baseline in the citalopram treatment group than in the placebo treatment group, beginning at week 1 and continuing at every observation point to the end of the study (effect size=2.9). The difference in response rate at week 8 between placebo (24%) and citalopram (36%) also was statistically significant. Citalopram treatment was well tolerated. Rates of discontinuation due to adverse events were comparable in the placebo and citalopram groups (5.9% versus 5.6%, respectively). Rhinitis, nausea, and abdominal pain were the only adverse events to occur with a frequency exceeding 10% in either treatment group.\n In this population of children and adolescents, treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated." ]

[ "15084618", "18485252", "2679397", "12649101" ]

[ "Phase III randomized trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer.", "Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer.", "[Prevention of stomatitis induced by anti-cancer drugs].", "Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study." ]

[ "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 evaluate the efficacy of pure natural honey as prophylaxis against radiochemotherapy-induced mucositis, through clinical scoring of oral and oropharyngeal mucositis, and culturing of pathogenic oral and oropharyngeal microbes.\n The study was done in Assiut University Hospital, Egypt, between January 2005 and July 2006. Forty patients diagnosed with head and neck cancer were entered into the trial. Enrolled patients were randomised to either the treatment group, receiving concomitant chemotherapy and radiotherapy (with a significant area of directly visible oral and/or oropharyngeal mucosa included in the radiation fields) plus prior topical application of pure natural honey, or the control group, receiving concomitant chemotherapy and radiotherapy without honey. Patients were evaluated clinically every week to assess development of radiation mucositis. Aerobic cultures and candida colonisation assessment were undertaken, via oral and oropharyngeal swabs, prior to and at the completion of irradiation, and when infection was evident.\n In the treatment group, no patients developed grade four mucositis and only three patients (15 per cent) developed grade three mucositis. In the control group, 13 patients (65 per cent) developed grade three or four mucositis (p < 0.05). Candida colonisation was found in 15 per cent of the treatment group and 60 per cent of the control group, either during or after radiotherapy (p = 0.003). Positive cultures for aerobic pathogenic bacteria were observed in 15 per cent of the treatment group and 65 per cent of the control group, during or after radiotherapy (p = 0.007).\n This study shows that prophylactic use of pure natural honey was effective in reducing mucositis resulting from radiochemotherapy in patients with head and neck cancer.", "A randomized control trial study was carried out to evaluate the effect of allopurinol mouth wash on stomatitis induced by chemotherapy in gynecologic patients. Chemotherapeutics used consisted of 5-FU+CDDP (PF) given to 10 patients and vincristine and actinomycin-D+cyclophosphamide (VAC) given to 5. Allopurinol mouth wash was prepared for patients to rinse their mouth with the solution 4-5 times daily before and after treatment with anti-cancer drugs. The Japan Society For Cancer Therapy's criteria for stomatitis were used. In the control group, stomatitis occurred in 9 of the 10 patients receiving PF therapy and in all of the 5 receiving VAC. In contrast, stomatitis was observed in only 2 of the 10 patients receiving PF therapy and 2 of the 5 VAC in the allopurinol-treated group. Allopurinol mouth wash showed a marked effect on stomatitis induced by chemotherapy.", "The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy.\n Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery.\n The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS).\n We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied." ]

[ "12074203", "1520054", "2669346", "59150", "9048790", "15808033", "2051002", "2043179", "1457907", "15808032", "3555580", "6346830", "11816439", "8021700", "16525097", "1298631" ]

[ "Effectiveness of quinine in treating muscle cramps: a double-blind, placebo-controlled, parallel-group, multicentre trial.", "Treatment of nocturnal leg cramps. A crossover trial of quinine vs vitamin E.", "Placebo-controlled trial of quinine therapy for nocturnal leg cramps.", "Prevention of muscle cramps in haemodialysis patients by quinine sulphate.", "Randomised controlled trial of hydroquinine in muscle cramps.", "Managing nocturnal leg cramps--calf-stretching exercises and cessation of quinine treatment: a factorial randomised controlled trial.", "A randomized controlled trial of quinidine in the treatment of cirrhotic patients with muscle cramps.", "[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.", "N-of-1 trials of quinine efficacy in skeletal muscle cramps of the leg.", "A quinine a day keeps the leg cramps away?", "A double-blind comparison of quinine sulphate and placebo in muscle cramps.", "Randomized comparison of quinine-clindamycin versus artesunate in the treatment of falciparum malaria in pregnancy.", "Efficacy of hydroquinine in preventing frequent ordinary muscle cramp outlasts actual administration.", "Effective treatment of uncomplicated Plasmodium falciparum malaria with azithromycin-quinine combinations: a randomized, dose-ranging study.", "Quinine loading dose in severe Falciparum malaria at Kenyatta National Hospital, Kenya." ]

[ "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.", "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.", "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.", "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.", "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.", "Quinine is a common treatment for nocturnal leg cramps but has potential side effects. An uncontrolled study suggested that calf-stretching exercises could prevent nocturnal leg cramps (night cramps) but these findings have never been confirmed.\n To assess the effect of calf-stretching exercises and cessation of quinine treatment for patients with night cramps taking quinine.\n Randomised controlled trial.\n Twenty-eight general practices in southern England.\n One hundred and ninety-one patients prescribed quinine for night cramps were randomised to one of four groups defined by two \"advice\" factors: undertake exercises and stop quinine. After 6 weeks they were advised that they could take quinine and undertake the exercises freely. Documentation of cramp at 12 weeks was achieved in 181 (95%) patients. Main outcome measures were: symptom burden score, and frequency of night cramps and quinine usage.\n At 12 weeks there was no significant difference in number of cramps in the previous 4 weeks (exercise = 1.95, 95% confidence interval [CI] = -3.01 to 6.90; quinine cessation = 3.45, 95% CI = -1.52 to 8.41) nor symptom burden or severity of cramps. However, after 12 weeks 26.5% (95% CI = 13.3% to 39.7%) more patients who had been advised to stop quinine treatment reported taking no quinine tablets in the previous week (odds ratio [OR] = 3.32, 95% CI = 1.37 to 8.06), whereas advice to do stretching exercises had no effect (OR = 0.73, 95% CI = 0.27 to 1.98).\n Calf-stretching exercises are not effective in reducing the frequency or severity of night cramps. Advising those on long-term repeat prescriptions to try stopping quinine temporarily will result in no major problems for patients, and allow a significant number to stop medication.", "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.", "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.", "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.", "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.", "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.", "In areas where multidrug-resistant Plasmodium falciparum (MDR-Pf) is prevalent, only quinine is known to be safe and effective in pregnant women. On the western border of Thailand, 7 days of supervised quinine (30 mg/kg daily) cures two-thirds of P. falciparum-infected women in the 2nd and 3rd trimesters of pregnancy. Artesunate is effective against MDR-Pf and the limited data on its use in pregnancy suggest it is safe. An open randomized comparison of supervised quinine (10 mg salt/kg every 8 h) in combination with clindamycin (5 mg/kg every 8 h) for 7 days (QC7) versus artesunate 2 mg/kg per day for 7 days (A7) was conducted in 1997-2000 in 129 Karen women with acute uncomplicated falciparum malaria in the 2nd or 3rd trimesters of pregnancy. There was no difference in the day-42 cure rates between the QC7 (n = 65) and A7 (n = 64) regimens with an efficacy of 100% in both, confirmed by parasite genotyping. The A7 regimen was also associated with less gametocyte carriage; the average person-gametocyte-weeks for A7 was 3 (95% CI 0-19) and for QC7 was 39 (95% CI 21-66) per 1000 person-weeks, respectively (P < 0.01). There was no difference in gastrointestinal symptoms between the groups but there was significantly more tinnitus in the QC7 group compared to the A7 group (44.9% vs 8.9%; RR 5.1; 95% CI 1.9-13.5; P < 0.001). The favourable results with quinine-clindamycin mean that there is a useful back-up treatment for women with falciparum malaria who experience quinine and artesunate failures in pregnancy. Adherence to the 7-day regimen and cost (US$18.50 per treatment) are likely to be the main obstacles to this regimen.", "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.", "Azithromycin, the most potent antimalarial macrolide antibiotic, is synergistic with quinine against Plasmodium falciparum in vitro. We assessed combinations of azithromycin and quinine against uncomplicated P. falciparum malaria at the Armed Forces Research Institute of Medical Sciences-Kwai River Clinical Center along the Thailand-Myanmar border, an area with a high prevalence of multidrug-resistant P. falciparum. Four regimens were assessed in an open-label dose-ranging design involving 61 volunteers. All received oral quinine (Q; 30 mg/kg/day divided every 8 hours for 3 days) with oral azithromycin (Az; 500 mg twice a day for 3 days, 500 mg twice a day for 5 days, or 500 mg three times a day for 3 days). A comparator group received quinine and doxycycline (Dx; 100 mg twice a day for 7 days). Study observation was 28 days per protocol. Sixty volunteers completed the study. Seven days of QDx cured 100% of the volunteers. One failure occurred in the lowest QAz regimen (on day 28) and none occurred in either of the two higher Az regimens. Cinchonism occurred in nearly all subjects. Overall, the azithromycin regimens were well tolerated, and no volunteers discontinued therapy. Three- and five-day azithromycin-quinine combination therapy appears safe, well tolerated, and effective in curing drug-resistant P. falciparum malaria. Further evaluation, especially in pediatric and obstetric populations, is warranted.", "From July 1989 to February 1990, 17 non-pregnant patients with severe falciparum malaria, aged 14 years and above received an initial intravenous quinine dihydrochloride loading dose of 20 mg/kg in 500 mls of normal saline or 5% dextrose infused over 4 hours followed by 100mg/kg infused 8 hourly for at least 24 hours. Sixteen comparable controls were similarly treated but without an initial loading dose. Oral quinine bisulfate 10mg/kg 8 hourly was substituted for a total of 7 days when patients were well enough. There was no significant difference in clinical and parasitological response between the two groups. Fever clearance time in hours was 44.00 +/- 13.92 (mean +/- SD) in the study group and 51.43 +/- 19.63 (mean +/- SD) in the control group (p > 0.05). Parasite clearance time in hours was 42.40 +/- 9.75 (mean +/- SD) in the study group and 47.05 +/- 7.69 (mean +/- SD) in the control group (p > 0.05). One patient from each group died. Mild toxic effects were common in both groups. Transient partial hearing loss occurred significantly more in the study than control group (p < 0.05). Hypoglycaemia during treatment occurred in 3 (18%) patients in the study group and 1 (6%) in the control group. The mean trough and peak plasma quinine levels in 3 patients per group was persistently higher than 9mg/L after first infusion. We conclude that though fairly well tolerated, quinine loading dose appears to have no advantage over the standard treatment for severe falciparum malaria at Kenyatta National Hospital, Nairobi, Kenya." ]

[ "16801465", "12137603", "17975231", "8167383", "10082500", "17591533", "15923569", "11431176", "14990637", "13678870", "8996151", "19176895", "12939417", "2200559", "22659994", "1296590", "10740141", "15917336", "15326237", "15659494", "11320369", "9314638", "9269212", "10955375", "10051289", "15077078", "10652036", "16421418", "11255809", "9848785", "17425758", "18371477", "11855793", "11092994", "8382753", "11347755", "1325010", "12761258", "11565518", "11328912", "9294465", "10690979", "8750152", "8335810", "11115082", "11573655" ]

[ "Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial.", "[The effects of angiotensin-converting enzyme inhibitor on IgA nephropathy and the influencing factors].", "N-acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre-existing moderate renal insufficiency.", "ACE inhibitor mediated reductions in renal size and microalbuminuria in normotensive, diabetic subjects.", "ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients.", "ACE inhibitors and persistent left ventricular hypertrophy after renal transplantation: a randomized clinical trial.", "Successful implementation of the randomized discontinuation trial design: an application to the study of the putative antiangiogenic agent carboxyaminoimidazole in renal cell carcinoma--CALGB 69901.", "Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy.", "Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines.", "Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial.", "Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer.", "Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial.", "A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis.", "Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases.", "A combination of galantamine and memantine modifies cognitive function in subjects with amnestic MCI.", "Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial.", "Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors.", "Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short-term, randomized, controlled trial.", "Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial.", "Docetaxel and continuous-infusion fluorouracil versus epirubicin, cisplatin, and fluorouracil for advanced gastric adenocarcinoma: a randomized phase II study.", "ADEPT: Addition of the AT1 receptor antagonist eprosartan to ACE inhibitor therapy in chronic heart failure trial: hemodynamic and neurohormonal effects.", "Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria.", "Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. The EUCLID Study Group.", "Meta-analysis of observed mortality data from all-controlled, double-blind, multiple-dose studies of losartan in heart failure. Losartan Heart Failure Mortality Meta-analysis Study Group.", "Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure.", "A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial.", "Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients.", "Multicycle dose-intensive chemotherapy for women with high-risk primary breast cancer: results of International Breast Cancer Study Group Trial 15-95.", "Prophylactic actinomycin D for high-risk complete hydatidiform mole.", "The antiproteinuric effect of angiotensin antagonism in human IgA nephropathy is potentiated by indomethacin.", "Enalapril/amlodipine combination in cyclosporine-treated renal transplant recipients: a prospective randomized trial.", "The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.", "Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study.", "Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy.", "Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants.", "Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes.", "Treatment of arterial hypertension in diabetic humans: importance of therapeutic selection.", "Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial.", "Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.", "The effect of ACE inhibitor and angiotensin II receptor antagonist therapy on serum uric acid levels and potassium homeostasis in hypertensive renal transplant recipients treated with CsA.", "Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group.", "Randomized pilot trial of postoperative aspirin in subarachnoid hemorrhage.", "Randomised study using IFN-alpha versus IFN-alpha plus coumarin and cimetidine for treatment of advanced renal cell cancer.", "Short-term effects of early intravenous treatment with a beta-adrenergic blocking agent or a specific bradycardiac agent in patients with acute myocardial infarction receiving thrombolytic therapy.", "ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis.", "Haemodynamic and renal effects of intravenous enalaprilat during coronary artery bypass graft surgery in patients with ischaemic heart dysfunction." ]

[ "Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function.\n We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13).\n Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.", "OBJECTIVE To investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) on IgA nephropathy(IgAN) and the factors influencing the therapeutic effects. METHODS 131 cases with IgAN diagnosed by renal biopsy were randomly divided into two groups: ACEI group (benazepril 10 mg/d) and non-ACEI group as control. The pathological changes in the kidney were analyzed using Lee SMK. RESULTS After 1 month treatment of ACEI, the levels of proteinuria and serum cholesterol decreased significantly, meanwhile those of serum albumin and total protein increased obviously in patients with IgAN(P < 0.05). The proteinuria level at the 3rd month after treatment was lower than that at the 1st month, but was same as that at the 18th month. While in the control group the proteinuria level increased and the clearance of creatinine decreased continuously during the observation (P < 0.05). The effects correlated positively with mesangial proliferation and negatively with course of the disease glomerular sclerosis in glomerulus and changes of small arterioles in the kidney. Normal blood pressare normal renal function I approximately II degree of Lee SMK I degee of interstitial changes minimal changes of small arterioles and mild glomerular sclerosis predicted better response to ACEI treatment than hypertension renal insufficiency V degree of Lee SMK IV degee of interstitial changes severe changes of small arterioles and massive glomerular sclerosis. CONCLUSIONS It is suggested that benezepril could definitely reduce the excretion of urinary protein and protect renal function of patients with IgAN and should be used as earlier as possible. Mesangial prolife ration glomerular sclerosis in glomerulus changes of small arterioles in kidney and course of the disease are the major influencing factors of ACEI treatment on IgAN.", "N-acetylcysteine may prevent acute kidney injury after cardiac surgery. To determine if N-acetylcysteine warrants definitive evaluation in a large multicentre trial, we evaluated its effects on a surrogate outcome, estimated glomerular filtration rate (eGFR), in a randomized trial.\n One-hundred-seventy-seven cardiac surgery patients with moderate pre-existing renal insufficiency (eGFR <or= 60 mLxmin(-1)) were recruited in a blinded (patients, clinicians, data-collectors) placebo-controlled randomized trial. Eighty-nine were randomized to N-acetylcysteine (100 mgxkg(-1) i.v. bolus, 20 mgxkg(-1)xhr(-1) infusion until four hours after cardiopulmonary bypass), and 88 to placebo. The primary outcome was the percent change in eGFR during the first 72 postoperative hours. Secondary outcomes included renal replacement therapy, mortality, atrial fibrillation, vasoactive medications, and adverse effects. A future multicentre trial was deemed to be warranted if N-acetylcysteine was associated with a percent change in eGFR that was 3.8 better (small benefit), and with an upper 95% confidence interval including 9.5 (moderate benefit).\n The median percent change in eGFR was 5.2% better (absolute difference) in the N-acetylcysteine arm (95% confidence interval 2.4% worse to 12.1% better; P=0.22). With regard to secondary outcomes, all-cause mortality was lower in the N-acetylcysteine arm (0% vs 8%; P=0.007).\n N-acetylcysteine did not cause a statistically significant improvement in postoperative eGFR in this single-centre study. Nonetheless, its treatment effect was consistent with a plausible small-to-moderate benefit. Given this finding, N-acetylcysteine should be definitively evaluated in a large randomized trial.", "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.", "Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the beta-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after 24 months in the atenolol group; P=NS for both groups). After 24 months, the change in urinary albumin excretion from baseline was -10+/-15 mg/d in the quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function.", "Interventional studies of left ventricular hypertrophy (LVH) in renal transplant recipients are scarce and to date evaluated only patients immediately after renal transplantation.\n Randomized controlled trial that assessed the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in regressing persistent LVH after successful transplantation.\n 70 renal transplant recipients (47 men; age, 30 to 68 years) without diabetes previously randomly assigned to either cyclosporine or tacrolimus therapy, with LVH persisting 3 to 6 months after transplantation.\n Subjects were randomly assigned to either lisinopril (ACE-inhibitor group; 36 patients) or no therapy (control group; 34 subjects).\n Main outcome was change in left ventricular mass index (LVMi) at month 18.\n A consistent decrease in both systolic (SBP) and diastolic blood pressure (DBP) was observed in both groups (between-group differences, -1.7 +/- 3.3 mm Hg; 95% confidence interval [CI], -4.8 to 8.2; P = 0.6 for SBP; 0.3 +/- 2.2 mm Hg; 95% CI, -4.8 to 4.1; P = 0.9 for DBP), whereas LVMi regressed more in the ACE-inhibitor group (between-group difference, 10.1 +/- 16.3 g/m(2.7); 95% CI, 4.2 to 16.1; P < 0.01). A significant interaction of ACE inhibitors with cyclosporine in affecting LVMi change was shown by means of post hoc multiple regression analysis (P < 0.01; differences between cyclosporine and tacrolimus group, 13.3 +/- 3.9 g/m(2.7); 95% CI, 5.3 to 21.2; P < 0.01 in the ACE-inhibitor group; 3.7 +/- 4.2 g/m(2.7); 95% CI, -4.7 to 12.2; P = 0.4 in the control group).\n Single-center study with small sample size. Interaction of ACE inhibitors with cyclosporine treatment emerged from post hoc analysis.\n A prolonged course of ACE-inhibitor therapy is effective in regressing the persistent LVH of renal transplant recipients by mechanisms independent of effects on BP. This regression seems to be at least in part the effect of an interaction between ACE inhibitors and cyclosporine.", "To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design.\n Recruited patients had a performance status of 0 to 2, minimal neuropathy or cerebellar dysfunction, measurable disease, and normal organ function. Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response. Protocol treatment was discontinued for unacceptable toxicity or progressive disease; patients with stable disease at the 16-week evaluation point were randomly assigned in a double-blind manner to continued CAI or placebo. The primary end point was the stable disease rate in the randomized groups.\n A total of 368 patients were accrued and received therapy. Ninety percent had a performance status of 0 or 1, 80% underwent a prior nephrectomy, and 41% had received no prior systemic therapy. Serious or life-threatening toxicity was experienced by 34%, with asthenia (15%) and neuropsychiatric difficulties (7%) being most common. At the randomization point, 51% of patients had progressed, 30% withdrew, 1% experienced a partial response, and 17% had stable disease and were randomly assigned. A Bayesian futility analysis utilizing the first 49 randomly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9% even under the most optimistic a priori assumptions, and further trial accrual was halted.\n CAI is inactive in RCC. The RDT design should be further explored for evaluating activity of putative disease stabilizing agents.", "Angiotensin-converting enzyme (ACE) inhibitors and AT1-receptor antagonists (ARAs) are widely administered to reduce urinary protein loss and slow the progression of proteinuric nephropathy to end-stage renal failure. Our group recently observed that the combination of ACE inhibitors and ARAs may have an additive antiproteinuric effect, which may occur because ACE inhibitors do not completely reduce angiotensin II (Ang II) production. Ang II is also produced by chymase. Thus, combination therapy better antagonizes the effects of Ang II. The purpose of this study is to ascertain whether the additive antiproteinuric effect of ACE inhibitors plus ARAs is dose dependent and related to the drug-induced reduction in systemic blood pressure. Therefore, enalapril (E; 10 mg/d) and losartan (LOS; 50 mg/d) were randomly administered alone and then in association; initial dosages were doubled when drugs were administered alone and in association. To determine the influence of the drug-dependent effect on reducing blood pressure and the reduction in urinary proteinuria, both ambulatory and office blood pressures were recorded. E and LOS administered alone reduced proteinuria by the same extent; no further reduction was observed when E and LOS alone were administered at a doubled dose. When E and LOS were coadministered, proteinuria decreased by a greater extent compared with E and LOS alone; an additional reduction in proteinuria was observed when combined therapy doses were doubled. The reduction in proteinuria was not correlated with clinical through blood pressure; however, reductions in diastolic and mean ambulatory blood pressures significantly correlated with the decrease in proteinuria, as well as with creatinine clearance. In conclusion, this study shows that combination therapy with E and LOS has an additive dose-dependent antiproteinuric effect that is likely induced by the drug-related reduction in systemic blood pressure. In normotensive proteinuric patients, it is likely that even a small reduction in systemic blood pressure may affect intraglomerular hemodynamics by a great extent because efferent arteriole regulation is hampered more completely by the coadministration of ACE inhibitors and ARAs.", "To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer.\n This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure.\n There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m(2); P =.55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (-8.59 v 1.85 g/cm(2); P =.033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P =.11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P =.0003) and fatigue (10% v 0%; P =.013).\n Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions.", "Angiotensin-converting-enzyme (ACE) inhibitors improve outcome of patients with chronic heart failure (CHF). A substantial proportion of patients, however, experience no benefit from ACE inhibitors because of previous intolerance. We aimed to find out whether candesartan, an angiotensin-receptor blocker, could improve outcome in such patients not taking an ACE inhibitor.\n Between March, 1999, and March, 2001, we enrolled 2028 patients with symptomatic heart failure and left-ventricular ejection fraction 40% or less who were not receiving ACE inhibitors because of previous intolerance. Patients were randomly assigned candesartan (target dose 32 mg once daily) or matching placebo. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was by intention to treat.\n The most common manifestation of ACE-inhibitor intolerance was cough (72%), followed by symptomatic hypotension (13%) and renal dysfunction (12%). During a median follow-up of 33.7 months, 334 (33%) of 1013 patients in the candesartan group and 406 (40%) of 1015 in the placebo group had cardiovascular death or hospital admission for CHF (unadjusted hazard ratio 0.77 [95% CI 0.67-0.89], p=0.0004; covariate adjusted 0.70 [0.60-0.81], p<0.0001). Each component of the primary outcome was reduced, as was the total number of hospital admissions for CHF. Study-drug discontinuation rates were similar in the candesartan (30%) and placebo (29%) groups.\n Candesartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors.", "We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin, and methotrexate (FAMTX) in previously untreated patients with advanced esophagogastric cancer.\n Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were randomized and analyzed for survival, tumor response, toxicity, and quality of life (QL).\n The overall response rate was 45% (95% confidence interval [CI], 36% to 54%) with ECF and 21% (95% CI, 13% to 29%) with FAMTX (P = .0002). Toxicity was tolerable and there were only three toxic deaths. The FAMTX regimen caused more hematologic toxicity and serious infections, but ECF caused more emesis and alopecia. The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX (P = .0009); at 1 year, 36% (95% CI, 27% to 45%) of ECF and 21% (95% CI, 14% to 29%) of FAMTX patients were alive. The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX (P = .00006). The global QL scores were better for ECF at 24 weeks, but the remaining QL data showed no differences between either arm of the study. Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $975 per life-year gained.\n The ECF regimen results in a survival and response advantage, tolerable toxicity, better QL and cost-effectiveness compared with FAMTX chemotherapy. This regimen should now be considered the standard treatment for advanced esophagogastric cancer.", "Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms.\n In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function.\n The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%).\n Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.", "To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS.\n A double-blind, placebo-controlled, multicenter randomized clinical trial was conducted. Participants with ALS (n = 296) were randomized (2:1) to receive topiramate (maximum tolerated dose up to 800 mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function as measured by the maximum voluntary isometric contraction (MVIC) strength of eight arm muscle groups. Secondary endpoints included safety and the rate of decline of forced vital capacity (FVC), grip strength, ALS functional rating scale (ALSFRS), and survival.\n Patients treated with topiramate showed a faster decrease in arm strength (33.3%) during 12 months (0.0997 vs 0.0748 unit decline/month, p = 0.012). Topiramate did not significantly alter the decline in FVC and ALSFRS or affect survival. Topiramate was associated with an increased frequency of anorexia, depression, diarrhea, ecchymosis, nausea, kidney calculus, paresthesia, taste perversion, thinking abnormalities, weight loss, and abnormal blood clotting (pulmonary embolism and deep venous thrombosis).\n At the dose studied, topiramate did not have a beneficial effect for patients with ALS. High-dose topiramate treatment was associated with a faster rate of decline in muscle strength as measured by MVIC and with an increased risk for several adverse events in patients with ALS. Given the lack of efficacy and large number of adverse effects, further studies of topiramate at a dose of 800 mg or maximum tolerated dose up to 800 mg/day are not warranted.", "Survival benefit from hepatic artery embolization (HAE) or hepatic arterial infusion chemotherapy (HAI) in patients with unresectable colorectal liver metastases has not previously been assessed in a randomized controlled trial. Sixty-one patients were randomized, 20 to receive no treatment, 22 to receive HAE, and 19 to receive HAI with 5-fluorouracil and degradable starch microspheres. Both treatments were acceptable to the patients in terms of low treatment morbidity rate. Median survival from diagnosis of metastases was 9.6 months for controls, 8.7 months for the HAE group and 13.0 months in the HAI group. There was no apparent survival benefit for the HAE group. The increased survival in the HAI group was observed in all the subgroups analysed but failed to reach statistical significance. The greatest observed benefit was achieved in the subgroup with less than 50 per cent hepatic replacement with tumour at presentation (median survival from diagnosis 10.0 months for controls, 10.2 months for HAE and 23.6 months for HAI); 36 per cent of patients developed extrahepatic disease recurrence. No significant benefit has been shown from either HAE or HAI, but a more carefully selected group of patients with only low volume hepatic disease may benefit from HAI therapy.", "Mild cognitive impairment (MCI) is etiologically heterogeneous, and a substantial proportion of MCI subjects will develop different dementia disorders. One subtype of this syndrome, amnestic MCI, occurs preferentially but not exclusively in prodromal AD and is characterized by defined deficits of episodic memory.\n For a 2-year, double-blinded, placebo-controlled study MCI patients, presenting with an amnestic syndrome but not necessarily based on presumed prodromal AD were randomized.\n Patients received (a) a combination of 16 mg galantamine plus 20 mg memantine, or (b) 16 mg galantamine alone or (c) placebo.\n The primary objective was to explore the differential impact of these interventions on the progression to dementia and on cognitive changes as measured by the ADAScog.\n After recruitment of 232 subjects, the trial was halted before reaching the planned sample size, because safety concerns arose in other studies with galantamine in MCI. This resulted in a variable treatment duration of 2-52 weeks. The statistical analysis plan was amended for studying cognitive effects of discontinuing the study medication, which was done separately for galantamine and memantine, and under double-blind conditions. There was one death, no unexpected severe adverse events, and no differences of severe adverse events between the treatment arms. The cognitive changes on the ADAScog were not different among the groups. Only for the subgroup of amnestic MCI with presumed AD etiology, a significant improvement of ADAScog score over placebo before the discontinuation of medication was observed, while amnestic MCI presumably due to other etiologies showed no cognitive changes with broad variation. Cognitive improvement was numerically larger in the combination treatment group than under galantamine alone. Patients who received placebo declined as expected. Discontinuation of galantamine, either as part of the combination regimen or as mono treatment, resulted in a transient decline of the ADAScog score in amnestic MCI of presumed AD etiology, while discontinuation of Memantine did not change the cognitive status.\n In an interrupted trial with amnestic MCI subjects the combination of galantamine plus memantine were generally well tolerated. In the subgroup of MCI subjects with presumed AD etiology, a cognitive benefit of a short-term combination treatment of galantamine plus memantine was observed, and cognitive decline occurred after discontinuation of galantamine.", "A multicentric randomized study that compared patients who received intrahepatic arterial infusion (HAI) to a group of patients who did not receive HAI (control group) was performed for unresectable hepatic metastases from primary colorectal carcinoma.\n One hundred sixty-six patients were assigned randomly to HAI of floxuridine (5 fluoro-2'deoxyuridine [FUDR]) 0.3 mg/kg/d for 14 days every 4 weeks or to the control group; this latter group, depending on the investigator's choice, was either under observation or received systemic fluorouracil (5-FU). The same regimen of systemic 5-FU also was administered to the HAI group in the event of extrahepatic progression. No crossover from the control group to the HAI group was permitted. The mean duration of follow-up was 54 months (range, 31 to 72), and 163 patients were analyzed.\n A significant improvement was observed in the survival rate for the 81 patients assigned to HAI group (P less than .02) with a 1-year survival rate of 64% versus 44% in the control group (82 patients). The 2-year survival rate was 23% versus 13%. The median survival was 15 months versus 11 months for the HAI group and the control group, respectively. Survival was better for patients with a less than 30% liver involvement, and for those treated in more specialized centers. The hepatotoxic effects of HAI were observed in 47 patients (chemical hepatitis [n = 28], and biliary sclerosis [n = 19]). The 1-year rate of sclerosing cholangitis was equal to 25%. Gastrointestinal toxicity was infrequent and consisted of gastritis or diarrhea.\n Therapy with HAI of FUDR improves the survival of patients with liver metastases over colorectal carcinoma. However, the methods that are used to diminish the toxicity of HAI and efficient systemic chemotherapy, such as a combination of 5-FU and leucovorin, are required to prevent extrahepatic metastases.", "Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors.\n Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%).\n The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%).\n Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.", "Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy (DN), albuminuria and progression of renal disease are not completely halted by these agents. Therefore, it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches. This study tested the hypothesis that the combination of pentoxifylline (PTF) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect. Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for >1 yr were randomly assigned to receive the addition of 1200 mg of PTF daily (n = 30) or to a control group (n = 31). Baseline characteristics were similar between groups, and correlation analysis showed a significant association between urinary albumin excretion (UAE) and urinary TNF-alpha (R = 0.53, P < 0.001). After 4 mo, albuminuria showed a significant decrease in patients who received PTF, from 900 mg/24 h (466 to 1542 mg/d) to 791 mg/24 h (309 to 1400 mg/d; P < 0.001), whereas no significant changes were observed in the control group: 920 mg/24 h (450 to 1489 mg/d) at baseline, and 900 mg/24 h (428 to 1800 mg/d) at the end of the study. The mean percentage variation of UAE in the treatment and control groups was -16.7 and 5.5%, respectively (between-group comparison, P < 0.001). This additive antiproteinuric effect was not dependent on changes in BP or metabolic control. However, both serum and urinary levels of TNF-alpha also decreased in patients who received PTF, from 6.4 pg/ml (2.1 to 9.7) and 16 pg/mg (8 to 29) at baseline to 4.6 pg/ml (0.4 to 9) and 14.2 pg/mg (3 to 26) at the end of the study, respectively (P < 0.01), without significant variations in control patients. Moreover, regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-alpha in patients who were treated with PTF (R = 0.49, P < 0.001). In conclusion, administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-alpha excretion.", "To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI).\n A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations.\n Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient.\n Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.", "A combination of docetaxel and fluorouracil (DF) was evaluated in an outpatient setting and compared with epirubicin, cisplatin, and fluorouracil (ECF), which served as an internal control arm to avoid selection bias.\n Patients with metastatic or locally advanced gastric adenocarcinoma without prior chemotherapy were randomly assigned to receive either ECF (epirubicin 50 mg/m(2) day 1, cisplatin 60 mg/m(2) day 1, and fluorouracil 200 mg/m(2) days 1 through 21, every 3 weeks) or DF (docetaxel 75 mg/m(2) day 1, and fluorouracil 200 mg/m(2) days 1 through 21, every 3 weeks).\n Ninety patients were randomly assigned. Toxicity was rarely severe. Major toxic effects included diarrhea, stomatitis, and leukopenia in the DF arm and nausea, vomiting, and leukopenia in the ECF arm. Forty-three of 45 patients in each arm were assessable. In the DF arm, two patients (4.4%, intent to treat) experienced a confirmed complete tumor remission as best response, and 15 patients (33.3%) experienced a confirmed partial remission (overall response rate [ORR], 37.8%; 95% CI, 25.9% to 51.9%). Two patients (4.4%) in the ECF arm showed confirmed complete remission, and 14 (31.1%) showed confirmed partial remission (ORR, 35.6%; 95% CI, 24.8% to 48.7%). For the DF and ECF arms, the median survival was 9.5 and 9.7 months, and the median time to tumor progression 5.5 and 5.3 months, respectively.\n DF can be safely given in an ambulant setting. Compared with ECF, the dual combination of DF shows promising efficacy and may be an alternative treatment option that avoids cisplatin.", "Persistent activation of the renin-angiotensin-aldosterone-system (RAAS) is known to occur in patients with chronic heart failure (CHF) despite treatment with angiotensin-converting enzyme inhibitor (ACE) therapy. When added to ACE inhibitors, angiotensin II type 1 (AT1) antagonists may allow more complete blockade of the RAAS and preserve the beneficial effects of bradykinin accumulation not seen with AT1 receptor blockade alone.\n Thirty-six patients with stable New York Heart Association class II-IV CHF receiving ACE inhibitor therapy were randomly assigned in a double-blind manner to receive either eprosartan, a specific competitive AT1 receptor antagonist (400 to 800 mg daily, n = 18) or placebo (n = 18) for 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF) as measured by radionuclide ventriculography, and secondary measures were central hemodynamics assessed by Swan-Ganz catheterization and neurohormonal effects.\n There was no change in LVEF with eprosartan therapy (mean relative LVEF percentage change [SEM] +10.5% [9.3] vs +10.1% [5.0], respectively; difference, 0.4; 95% confidence interval [CI], -20.8 to 21.7; P =.97). Eprosartan was associated with a significant reduction in diastolic blood pressure and a trend toward a reduction in systolic blood pressure compared with placebo (-7.3 mm Hg [95% CI, -14.2 to -0.4] diastolic; -8.9 mm Hg [95% CI, -18.6 to 0.8] systolic). No significant change in heart rate or central hemodynamics occurred during treatment with eprosartan compared with placebo. A trend toward an increase in plasma renin activity was noted with eprosartan therapy. Eprosartan was well tolerated, with an adverse event profile similar to placebo, whereas kidney function remained unchanged.\n When added to an ACE inhibitor, eprosartan reduced arterial pressure without increasing heart rate. There was no change in LVEF after 2 months of therapy with eprosartan.", "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.", "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.", "Clinical studies of heart failure utilizing losartan, an angiotensin-II receptor antagonist, found that this drug is well tolerated and demonstrates hemodynamic, neurohormonal, and symptomatic improvement. To assess all-cause mortality in heart failure patients treated with losartan, a meta-analysis including 1,896 patients was performed on 6 controlled, double-blind, multiple-dose studies, regardless of sample size or duration of follow-up. A combination of logarithmic (log) odds ratios with a continuity correction was utilized for the meta-analysis. Treatment groups were comparable with regard to demographic characteristics, heart failure characteristics, and concomitant cardiovascular therapies. Concomitant use of open-label angiotensin-converting enzyme (ACE) inhibitors was not allowed in any study. The mean left ventricular ejection fraction obtained in individual studies ranged from 23% to 31%. Seven hundred forty patients were randomized to control therapy and 1,154 patients were randomized to losartan therapy. There were 36 deaths (3.12%) in the losartan groups compared with 47 in the control groups (6.35%) during the double-blind periods. The odds of dying in the losartan groups were 0.51 times (0.31 to 0.81) that of dying in the control groups (p = 0.004). In this analysis, treatment with losartan provided a beneficial effect upon survival. However, because the number of deaths in these studies is relatively small and the follow-up relatively short, a large confirmatory study is needed to assess the mortality benefit of losartan compared with an ACE inhibitor.", "Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT1) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT1 receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown.\n Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V(O2)) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V(O2) at baseline and after 3 and 6 months were 13.5+/-0.6, 15.1+/-1.0, and 15.7+/-1.1 mL. kg-1. min-1, respectively, in patients receiving losartan and 14.1+/-0.6, 14.3+/-0.9, and 13.6+/-1.1 mL. kg-1. min-1, respectively, in patients receiving placebo (P<0.02 for treatment group-by-time interaction). Functional class improved by at least one NYHA class in 9 of 16 patients receiving losartan and 1 of 17 patients receiving placebo.\n Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors.", "Atrial fibrillation (AF) frequently occurs after cardiac surgical procedures, and beta-blockers, sotalol, and amiodarone may reduce the frequency of AF after open heart surgery. This pilot trial was designed to test whether each of the active oral drug regimens is superior to placebo for prevention of postoperative AF and whether there are differences in favor of 1 of the preventive strategies.\n We conducted a randomized, double-blinded, placebo-controlled trial in which patients undergoing cardiac surgery in the absence of heart failure and without significant left ventricular dysfunction (n = 253; average age, 65 +/- 11 years) received oral amiodarone plus metoprolol (n = 63), metoprolol alone (n = 62), sotalol (n = 63), or placebo (n = 65). Patients receiving combination therapy (amiodarone plus metoprolol) and those receiving sotalol had a significantly lower frequency of AF (30.2% and 31.7%; absolute difference, 23.6% and 22.1%; odds ratios [OR], 0.37 [95% CI, 0.18 to 0.77, P <.01 vs placebo] and 0.40 [0.19 to 0.82, P =.01 vs placebo]) compared with patients receiving placebo (53.8%). Treatment with metoprolol was associated with a 13.5% absolute reduction of AF (P =.16; OR, 0.58 [0.29 to 1.17]. Treatment effects did not differ significantly between active drug groups. Adverse events including cerebrovascular accident, postoperative ventricular tachycardia, nausea, and dyspepsia, in hospital death, postoperative infections, and hypotension, were similar among the groups. Bradycardia necessitating dose reduction or drug withdrawal occurred in 3.1% (placebo), 3.2% (combined amiodarone and metoprolol; P =.65 vs placebo), 12.7% (sotalol; P <.05 vs placebo), and 16.1% (metoprolol; P <.05 vs placebo). Patients in the placebo group had a nonsignificantly longer length of hospital stay as compared with the active treatment groups (13.1 +/- 8.9 days vs 11.3 +/- 7; P =.10), with no significant difference between the active treatment groups.\n Oral active prophylaxis with either sotalol or amiodarone plus metoprolol may reduce the rate of AF after cardiac surgery in a population at high risk for postoperative AF. Treatment with metoprolol alone resulted in a trend to a lower risk for postoperative AF.", "Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients.\n In hypertensive type 2 diabetic patients, treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, the long-term renal effects of ACE inhibitors in these patients remain inconclusive. In 1989, we commenced a placebo-controlled, double-blind, randomized study to examine the anti-albuminuric effects of enalapril versus nifedipine (slow release) in 102 hypertensive, type 2 diabetic patients. These patients have been followed up for a mean trial duration of 5.5 +/- 2.2 years. We examined the determinants, including the effect of ACE inhibition on clinical outcomes in these patients.\n After a six-week placebo-controlled, run-in period, 52 patients were randomized double-blind to receive nifedipine (slow release) and 50 patients to receive enalapril. After the one-year analysis, which confirmed the superior anti-albuminuric effects of enalapril (-54%) over nifedipine (+11%), all patients were continued on their previously assigned treatment with informed consent. They were subdivided into normoalbuminuric (N = 43), microalbuminuric (N = 34), and macroalbuminuric (N = 25) groups based on two of three 24-hour urinary albumin excretion (UAE) measurements during the run-in period. Renal function was shown by the 24-hour UAE, creatinine clearance (CCr), and the regression coefficient of the yearly plasma creatinine reciprocal (beta-1/Cr). Clinical endpoints were defined as death, cardiovascular events, and/or renal events (need for renal replacement therapy or doubling of baseline plasma creatinine).\n In the whole group, patients treated with enalapril were more likely to revert to being normoalbuminuric (23.8 vs. 15.4%), and fewer of them developed macroalbuminuria (19.1 vs. 30.8%) compared with the nifedipine-treated patients (P < 0.05). In the microalbuminuric group, treatment with enalapril (N = 21) was associated with a 13.0% (P < 0.01) reduction in 24-hour UAE compared with a 17.3% increase in the nifedipine group (N = 13). In the macroalbuminuric patients, enalapril treatment (N = 11) was associated with stabilization compared with a decline in renal function in the nifedipine group, as shown by the beta-1/Cr (0.65 +/- 4.29 vs. -1.93 +/- 2.35 1/micromol x 10-3, P < 0.05) after adjustment for baseline values. Compared with the normoalbuminuric and microalbuminuric patients, those with macroalbuminuria had the lowest mean CCr (75.5 +/- 24.1 vs. 63.5 +/- 21.3 vs. 41.9 +/- 18.5 mL/min, P < 0.001) and the highest frequency of clinical events (4.7 vs. 5.9 vs. 52%, P < 0. 001). On multivariate analysis, beta-1/Cr (R2 = 0.195, P < 0.001) was independently associated with baseline HbA1c (beta = -0.285, P = 0.004), whereas clinical outcomes (R2 = 0.176, P < 0.001) were independently related to the mean low-density lipoprotein cholesterol (beta = 2.426, P = 0.018), high-density lipoprotein cholesterol (beta = -8.797, P = 0.03), baseline UAE (beta = 0.002, P = 0.04), and mean CCr during treatment (beta = -0.211, P = 0.006).\n In this prospective cohort analysis involving 102 hypertensive, type 2 diabetic patients with varying degrees of albuminuria followed up for a mean duration of five years, we observed the importance of good metabolic and blood pressure control on the progression of albuminuria and renal function. Treatment with enalapril was associated with a greater reduction in albuminuria than with nifedipine in the entire patient group, and especially in those with microalbuminuria. In the macroalbuminuric patients, the rate of deterioration in renal function was also attenuated by treatment with enalapril.", "To compare adjuvant dose-intensive epirubicin and cyclophosphamide chemotherapy administered with filgrastim and progenitor cell support (DI-EC) with standard-dose anthracycline-based chemotherapy (SD-CT) for patients with early-stage breast cancer and a high risk of relapse, defined as stage II disease with 10 or more positive axillary nodes; or an estrogen receptor-negative or stage III tumor with five or more positive axillary nodes.\n Three hundred forty-four patients were randomized after surgery to receive seven cycles of SD-CT over 22 weeks, or three cycles of DI-EC (epirubicin 200 mg/m2 plus cyclophosphamide 4 gm/m2 with filgrastim and progenitor cell support) over 6 weeks. All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS).\n After a median follow-up of 5.8 years (range, 3 to 8.4 years), 188 DFS events had occurred (DI-EC, 86 events; SD-CT, 102 events). The 5-year DFS was 52% for DI-EC and 43% for SD-CT, with hazard ratio of DI-EC compared with SD-CT of 0.77 (95% CI, 0.58 to 1.02; P = .07). The 5-year overall survival was 70% for DI-EC and 61% for SD-CT, with a hazard ratio of 0.79 (95% CI, 0.56 to 1.11; P = .17). There were eight cases (5%) of anthracycline-induced cardiomyopathy (two fatal) among those who received DI-EC. Women with hormone receptor-positive tumors benefited significantly from DI-EC.\n There was a trend in favor of DI-EC with respect to disease-free survival. A larger trial or meta-analysis will be required to reveal the true effect of dose-intensive therapy.", "To evaluate the effectiveness of one course of prophylactic actinomycin D in reducing the malignant sequelae requiring chemotherapy in high-risk complete hydatidiform mole (CHM).\n A double-blind, randomized, controlled clinical trial was carried out at King Chulalongkorn Memorial Hospital. Sixty cases of CHM classified as high risk were recruited and randomly allocated to a chemoprophylactic or control group. Within one week after evacuation of molar tissues, actinomycin D was administered in the chemoprophylactic group. Patients in the control group were given only intravenous fluid and analgesic drugs. The number of patients with malignant sequelae who required therapeutic chemotherapy after evacuation of hydatidiform mole in each group was recorded.\n The incidence of malignant sequelae was 13.8% (95% confidence interval [CI] = 3.9-31.7%) in the chemoprophylactic group and 50.0% (95% CI = 31.3-68.7%) in the control group. The risk reduction of malignant sequelae with one course of actinomycin D chemoprophylaxis in high-risk CHM was 72.4% (95% CI = 26.7-89.6%) (P = .005). The side effects of prophylactic chemotherapy were stomatitis, nausea/vomiting, sore throat with oral ulcer and hair loss.\n One course of actinomycin D given as chemoprophylaxis decreased by 72.4% malignant sequelae after evacuation of molar tissue in patients with high-risk CHM. This may be particularly beneficial in patients with high-risk CHM who cannot be followed closely, whose compliance is in question and for whom hormonal follow-up is not available or unreliable.", "Evidence is available from animal and human studies that protein traffic through the glomerular capillary has a pathogenetic role in subsequent renal damage and that angiotensin-converting enzyme (ACE) inhibitors appear superior to other drugs in lowering proteinuria and the rate of renal function decline. This study compares the effect of ACE inhibition or angiotensin II (AngII) receptor blockade on urinary protein excretion and renal hemodynamics in 20 patients with IgA glomerulonephritis randomized to receive enalapril (20 mg/d) or irbesartan (100 mg/d) for 28 d in a double-blind study with two parallel groups. This study also evaluated whether addition of indomethacin (75 mg twice a day) to each of the two treatments resulted in a more potent antiproteinuric effect. Enalapril alone reduced total protein excretion (61% change from baseline) and fractional clearance of albumin without changes in GFR and minor elevation in renal plasma flow. Also, patients randomized to receive the AngII receptor antagonist irbesartan for 28 d had lower proteinuria (55% change from baseline) and fractional clearance of albumin at the end of the treatment period with similar renal hemodynamic changes. When indomethacin was added to enalapril treatment, a further significant reduction in urinary proteins and fractional albumin clearance was observed. In patients given irbesartan, the addition of indomethacin further reduced proteinuria and fractional clearance of albumin. The combined therapy with enalapril or irbesartan and indomethacin did not significantly affect GFR and renal plasma flow compared with baseline. These findings indicate that in patients with IgA glomerulonephritis the antiproteinuric effect of blocking AngII activity by either ACE inhibitors or AngII receptor antagonists is potentiated by indomethacin, an effect that occurred without impairment of renal function.", "Most hypertensive renal transplant recipients require two or more antihypertensive medications to achieve blood pressure control. However, which medications must be combined is still a matter of debate.\n A prospective randomized open-label blinded evaluation trial comparing the six-month effects of the amlodipine-enalapril combination (n = 32) vs. enalapril alone (n = 33) and vs. amlodipine alone (n = 34) on arterial pressure, renal function, albuminuria and tolerability.\n At six months, diastolic arterial pressure was more adequately controlled (i.e., <90 mmHg) in the combination group than in the amlodipine and enalapril groups (100% vs. 82.4% and 84.8%, respectively, p = 0.038). The same trend was observed for systolic arterial pressure (65.6% vs. 58.8% and 51.5%, NS). The six-month change in albuminuria was similar in the combination group and in the enalapril group (-64.7% vs. -59.5%); however, patients in the combination group exhibited a greater reduction in albuminuria than in the amlodipine group (-64.7% vs. -29.0%, p = 0.002). As compared with baseline values, serum creatinine and potassium remained unchanged in the combination group, whereas they increased by 9 +/- 12 micromol/L (p = 0.01) and by 0.2 +/- 0.4 mmol/L (p < 0.01), respectively, in the enalapril group. The cyclosporine trough levels remained unchanged in the combination group, but increased in the amlodipine group.\n Angiotensin-converting enzyme inhibitor (ACEI)-calcium-channel blocker (CCB) combination controls arterial pressure more adequately than ACEI alone or CCB alone, reduces albuminuria and may prevent the ACEI-induced initial rise in serum creatinine.", "Mild and moderate chronic kidney disease (CKD) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention (PCI). Therapy with clopidogrel decreases adverse events in large patient populations. Therefore, we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD.\n Two thousand two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed. Patients were randomly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopidogrel 75 mg/d for a year versus a placebo loading dose at the time of the PCI procedure and clopidogrel 75 mg/d for 28 days and placebo for the remainder of a year. Patients were categorized by their estimated creatinine clearance (>90 [normal, n = 999], 60-89 [mild CKD, n = 672], <60 mL/min [moderate CKD, n = 331]).\n Diminished renal function was associated with worse outcomes. Patients with normal renal function who received 1 year of clopidogrel had a marked reduction in death, myocardial infarction, or stroke compared with those who received placebo (10.4% vs 4.4%, P < .001), whereas patients with mild and moderate CKD did not have a significant difference in outcomes with clopidogrel therapy versus placebo (mild: 12.8% vs 10.3%, P = .30; moderate: 13.1% vs 17.8%, P = .24). Clopidogrel use was associated with an increased relative risk of major or minor bleeding, but this increased risk was not different based on renal function (relative risk 1.2, 1.3, 1.1).\n Clopidogrel in mild or moderate CKD patients may not have the same beneficial effect as it does in patients with normal renal function, but was not associated with a greater relative risk of bleeding based on renal function. Further studies are needed to define the role of clopidogrel therapy in patients with CKD.", "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.", "The urinary podocyte is postulated to be a marker for estimation of the severity of active glomerular injury and a predictor of disease progression in children with glomerulonephritis. Non-dihydropyridine calcium antagonist, including verapamil, reduce proteinuria to an extent similar to that of the angiotensin-converting enzyme inhibitor (ACEI), including trandolapril, but to a greater extent than other antihypertensives. Angiotensin (Ang) II receptor antagonists, including candesartan cilexetil, show potent and long-term preventive effects against the progression of renal injury. The aim of the present study is to assess whether verapamil, trandolapril and candesartan cilexetil affect proteinuria and urinary podocytes in patients with IgA nephropathy. Thirty-two normotensive patients aged 18-54 years with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (1-3 g/day), and normal renal function (creatinine clearance >80 ml/min) were studied. Twenty patients with diffuse mesangial proliferative glomerulonephritis (non-IgA PGN) and 20 healthy controls were also included in this study. The number of urinary podocytes in patients with advanced IgA nephropathy (n = 16) was significantly higher than that in patients with the disease in the mild stage (n = 16) (p < 0.01) or in patients with non-IgA PGN (p < 0.01). Urinary podocytes were not detected in healthy controls. The 32 patients with IgA nephropathy were randomly divided into four treatment groups: those treated with verapamil (120 mg/day, n = 8); those treated with trandolapril (2 mg/day, n = 8); those treated with candesartan cilexetil (8 mg/day, n = 8), and those given a placebo (n = 8). Treatment continued for 3 months. Antiproteinuric response in the trandolapril group was similar to that in the candesartan cilexetil group (-38 vs. -40%). The action of trandolapril or candesartan cilexetil was greater than that of verapamil (p < 0.01). Reduction in the number of urinary podocytes from baseline was significantly greater in patients treated with trandolapril or candesartan cilexetil than in patients treated with verapamil (p < 0.01). However, there was no difference between patients treated with trandolapril and those treated with candesartan cilexetil. Proteinuria and urinary podocytes were unaffected in the placebo group. These data suggest that urinary podocytes may be a marker of disease activity in adult patients with IgA nephropathy and that trandolapril and candesartan cilexetil are more effective than verapamil in reducing the number of podocytes.\n Copyright 2000 S. Karger AG, Basel", "The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 +/- 2 vs. 120 +/- 4 mm Hg), effective renal plasma flow (285 +/- 26 vs. 248 +/- 33 ml/min/1.73 m2) and glomerular filtration rate (59 +/- 4 vs. 61 +/- 8 ml/min/1.73 m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 +/- 3; CA -13 +/- 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 +/- 0.01% to 0.19 +/- 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "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.", "Some retrospective studies have suggested a beneficial influence of angiotensin-converting enzyme (ACE) inhibitors on the progression of IgA nephropathy (IgAN), but prospective and controlled studies demonstrating this effect are lacking. Forty-four patients with biopsy-proven IgAN, proteinuria > or = 0.5 g/d, and serum creatinine (SCr) < or = 1.5 mg/dl were randomly assigned either to receive enalapril (n = 23) or to a control group (n = 21) in whom BP was controlled with antihypertensives other than ACE inhibitors. Primary outcome was renal survival estimated by a 50% increase in baseline SCr. Secondary outcomes were the presence of a SCr > 1.5 mg/dl at the last visit and the evolution of proteinuria. Baseline clinical findings were similar at baseline between enalapril-treated and control group, and there were no differences in BP control during follow-up. Mean follow-up was 78 +/- 37 mo in the enalapril group and 74 +/- 36 mo in the control group. Three patients (13%) in the enalapril group and 12 (57%) in the control group reached the primary end point (P < 0.05). Kaplan-Meier renal survival was significantly better in enalapril group than in control group: 100% versus 70% after 4 yr and 92% versus 55% after 7 yr (P < 0.05). Three patients in the enalapril group (13%) and 11 (52%) in the control group showed SCr > 1.5 mg/dl at the last visit (P < 0.05). Proteinuria significantly decreased in the enalapril group, whereas it tended to increase in the control group (P < 0.001 between groups). In conclusion, ACE inhibitors significantly improve renal survival in proteinuric IgAN with normal or moderately reduced renal function.", "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.", "The angiotensin II (AT II) type I receptor antagonist losartan has been reported to increase urinary uric acid and potassium excretion. These effects might be beneficial in cyclosporin (CsA)-treated renal transplant recipients, who frequently suffer from hyperuricaemia and hyperkalaemia.\n In this prospective, open, randomized, two-way cross-over study we included 13 hypertensive CsA-treated patients after renal transplantation and administered either the angiotensin-converting enzyme (ACE) inhibitors enalapril or losartan. Laboratory parameters, 24-h urinary protein excretion, and mean 24-h arterial blood pressure (MAP) were checked after 3 weeks treatment with enalapril, after a wash-out period of 2 weeks, and before and after a 3-week treatment course with losartan.\n Both drugs slightly reduced MAP (losartan from 97+/-6 to 94+/-9 and enalapril to 93+/-8 mmHg). Serum potassium levels significantly increased during enalapril therapy (from 4.3+/-0.5 to 4.8+/-0.4 mmol/l, P<0.05), as did, although not significantly, uric acid concentrations (from 7.8+/-1.9 to 8.2+/-1.8 mg/dl, P=0.5). Losartan, on the contrary, only mildly affected serum potassium (4.3+/-0.5 vs 4.5+/-0.5 mmol/l, P=0.25) and serum uric acid decreased (from 7.8+/-2.4 to 7.3+/-1.8 mg/dl, P=0.6). Serum aldosterone and urinary aldosterone excretion were significantly reduced only during ACE inhibitor treatment, which might explain the variable effects on potassium homeostasis.\n Losartan may be a useful agent to reduce blood pressure and serum uric acid levels in renal transplant recipients treated with CSA: Furthermore, in this high-risk population, the effects on serum potassium levels are less marked with losartan than with enalapril.", "To evaluate if the timing of chest irradiation with respect to chemotherapy would influence survival and local and distant control in patients with limited-stage small-cell lung cancer (LSCLC).\n From 1981 to 1989, 199 consecutive patients with LSCLC were randomly allocated to receive initial chest irradiation (ICI; n = 99) or late chest irradiation (LCI; n = 100) given 18 weeks delayed. Both groups received the same nine cycles of combination chemotherapy: three cycles of cisplatin and etoposide and six cycles of cyclophosphamide, doxorubicin, and vincristine. In the first part of the study, prophylactic cranial irradiation (PCI) was only given to patients randomized to ICI, but after inclusion of 42 patients in the LCI arm, the protocol was changed, so that all patients received PCI independent of the timing of the chest irradiation (CI). A total of 157 patients received PCI with a radiation dose of 25 Gy in 11 fractions.\n The timing of radiotherapy had no significant effect on the 2-year overall survival rate (20% after ICI v 19% after LCI, P = .4) or the 2-year in-field recurrence rate (72% after ICI v 68% after LCI, P = .2). Median survival durations were 10.5 (ICI) and 12.0 (LCI) months. Similarly, no difference in the 2-year incidence of CNS recurrences was found between the 2 arms in patients who received PCI (19% after ICI v 13% after LCI, P = .24). Bone marrow toxicity was acceptable, as 15% developed World Health Organization (WHO) grade 4 leukocytopenia and 4% grade 4 thrombocytopenia. Grade 4 leukocytopenia was more pronounced in the ICI group. There was no difference in the frequency and severity of other toxicities between the 2 groups.\n Timing of CI did not significantly influence the incidence of in-field recurrences, CNS recurrences, or overall survival.", "To assess the safety and feasibility of a clinical trial on the effectiveness of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH).\n Several studies have indicated that increased platelet activity might be involved in the pathogenesis of delayed cerebral ischemia (DCI) after SAH.\n Fifty patients who had early surgery (< or =4 days) for a ruptured aneurysm were enrolled in this randomized, double-blind, placebo-controlled trial. Trial medication, consisting of suppositories with 100 mg ASA versus placebo, was started immediately after surgical clipping of the aneurysm and continued for 21 days. End points were functional outcome and quality of life at 4 months, clinical deterioration after operation, development of DCI, hypodense lesion on postoperative CT, and hemorrhagic complications.\n One-third of all patients with aneurysmal SAH were eligible for the trial. Fifteen of 26 patients receiving placebo deteriorated clinically versus 10 of 24 patients receiving ASA; 4 patients in each group deteriorated from DCI. Postoperative hypodensities on CT were observed in 27 patients, distributed equally in both groups. Functional outcome and quality-of-life scores were slightly in favor of patients who had received ASA, but not to a significant degree (p = 0.22). Two patients in the ASA group had an asymptomatic hemorrhagic complication, and one patient in the placebo group had a fatal and another a symptomatic hemorrhagic complication.\n This pilot study shows that a clinical trial of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH) is feasible and probably safe. The effectiveness of ASA on functional outcome and delayed cerebral ischemia has to be studied in a larger trial.", "Treatment results in patients with metastatic renal cell cancer (RCC) are still extremely unsatisfactory. Rates of response to IFN-alpha monotherapy and/or IL-2 mono/combination therapy vary between 10% and 20%. Coumarin (Cum) together with cimetidine (Cim) has yielded objective responses in 20%-33% of patients with RCC, according to two recent phase II studies.\n In the present study 148 patients with metastatic RCC were randomised to receive either IFN-alpha (5 MU 5 x weekly s.c.) + coumarin (100 mg/d p.o.) + cimetidine (3 x 400 mg/d p.o.), or IFN-alpha-monotherapy (5 MU 5 x weekly s.c.).\n Of the 148 patients in the study 137 were evaluable for response. No differences in remission rates (RR IFN-alpha + Cum + Cim 17.1% and IFN-alpha 20.8%) or survival times (median survival 9 months and 8 months, respectively) were found between these two treatment arms.\n This study confirms that INFN-alpha has antitumoral activity in RCC. Adding coumarin + cimetidine to IFN-alpha in the dose and regimen prescribed in this study did not increase response rates or survival.", "This study was conducted to explore mechanisms that could explain the possible clinical benefit of early administration of a beta 1-selective adrenoreceptor blocking agent or a bradycardiac drug as adjunct to thrombolysis in acute myocardial infarction.\n The effects of beta-blockers given concomitantly with thrombolytic therapy in patients with acute myocardial infarction have not been fully examined. The potential role of specific bradycardiac agents lacking negative inotropism as an alternative to beta-blockers in this setting has never been studied in humans.\n In a double-blind study, we examined the effects of early intravenous and continued oral administration of a beta-blocker (atenolol), a specific bradycardiac agent (alinidine) or placebo on left ventricular function, late coronary artery patency, infarct size, exercise capacity and incidence of arrhythmias.\n A total of 292 patients with acute myocardial infarction of < or = 5 h duration and without contraindications to thrombolytic or beta-blocker therapy were studied. Of these, 100 were allocated to treatment with atenolol (5 to 10 mg intravenously followed by 25 to 50 mg orally every 12 h), 98 to alinidine (20 to 40 mg intravenously followed by 20 to 40 mg orally every 8 h) and 94 to placebo. All patients received 100 mg of alteplase over 3 h and full intravenous heparinization. No significant differences in coronary artery patency, global ejection fraction or regional wall motion were observed at 10 to 14 days among the three groups. Likewise, enzymatic and scintigraphic infarct size were also very similar. Neither atenolol nor alinidine was associated with a significant reduction in the incidence of arrhythmias during the 1st 24 h. No significant differences in clinical events were observed, with the exception of a greater incidence of nonfatal pulmonary edema in the atenolol group (6% vs. 1% in the alinidine group and 0% in the placebo group, p = 0.021).\n In the absence of contraindications, the administration of a beta-blocker or a specific bradycardiac agent together with thrombolytic therapy was safe. In this limited number of patients, these agents did not appear to enhance myocardial salvage or preservation of left ventricular function or to reduce the incidence of major arrhythmias in the early phase of infarction.", "It has been postulated that angiotensin-converting enzyme inhibitor/angiotensin receptor antagonist (ACEI/ATRA) may decrease proteinuria in patients with glomerulonephritis by its action on the glomerular basement membrane. We therefore studied the relationship between the response of patients with IgA nephritis (IgAN) to ACEI/ATRA therapy by decreasing proteinuria and its effect on the selectivity index (SI) in these patients.\n Forty-one patients with biopsy-proven IgAN entered a control trial, with 21 in the treatment group and 20 in the control group. The entry criteria included proteinuria of 1 g or more and/or renal impairment. Patients in the treatment group received ACEI/ATRA or both with three monthly increases in dosage. In the control group, hypertension was treated with atenolol, hydrallazine, or methyldopa. The following tests were performed at three monthly intervals: serum creatinine, total urinary protein, SI, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and low molecular weight (LMW) proteinuria.\n After a mean duration of therapy of 13 +/- 5 months, in the treatment group, there was no significant change in serum creatinine, proteinuria, or SI, but in the control group, serum creatinine deteriorated from 1.8 +/- 0.8 to 2.3 +/- 1.1 mg/dL (P < 0.05). Among the 21 patients in the treatment group, 10 responded to ACEI/ATRA therapy determined as a decrease in proteinuria by 30% (responders), and the other 11 did not respond (nonresponders). Among the responders, SI improved from a mean of 0.26 +/- 0.07 to 0.18 +/- 0. 07 (P < 0.001), indicating a tendency toward selective proteinuria. This was associated with an improvement in serum creatinine from mean 1.7 +/- 0.6 to 1.5 +/- 0.6 mg/dL (P < 0.02) and a decrease in proteinuria from a mean of 2.3 +/- 1.1 to 0.7 +/- 0.5 g/day (P < 0. 001). After treatment, proteinuria in the treatment group (1.8 +/- 1. 6 g/day) was significantly less than in the control group (2.9 +/- 1. 8 g/day, P < 0.05). The post-treatment SI in the responder group (0. 18 +/- 0.07) was better than that of the nonresponder group (0.33 +/- 0.11, P < 0.002). Eight out of 21 patients in the treatment group who had documented renal impairment had improved renal function compared with two in the control group (chi2 = 4.4, P < 0. 05). Of the eight patients in the treatment group who improved their renal function, three normalized their renal function compared with one from the control group.\n Our data suggest that ACEI/ATRA therapy may be beneficial in patients with IgAN with renal impairment and nonselective proteinuria, as such patients may respond to therapy with improvement in protein selectivity, decrease in proteinuria, and improvement in renal function. ACEI/ATRA therapy probably modifies pore size distribution by reducing the radius of large unselective pores, causing the shunt pathway to become less pronounced, resulting in less leakage of protein into the urine.", "Renal dysfunction occurring after open heart surgery is multifactorial in origin but activation of the renin-angiotensin system may have a prominent role. Fourteen patients with ischaemic heart dysfunction scheduled for elective coronary artery bypass graft (CABG) surgery were allocated to a treatment group [enalaprilat for 2 days; ACEI (angiotensin-converting enzyme inhibitor) group, n=7] or a control group (n=7). The cardiac index was significantly higher in ACEI-treated patients than in the controls before and after cardiopulmonary bypass (CPB) (P<0.05) and on postoperative day 2 (P<0.05). The systemic vascular resistance was significantly lower in the ACEI-treated patients than in the controls before and after CPB (P<0.05). Renal plasma flow, measured as [131I]orthoiodohippuran clearance (ClH), was higher in the ACEI group than in the control group before CPB, as was endogenous creatinine clearance after CPB (P<0.05). On post-operative day 7, ClH was significantly higher in the ACEI group than in the control group (P<0.05). Plasma renin activity and vasopressin concentration increased in both groups during CPB (P<0.05). The study demonstrates that administration of an i.v. ACEI, enalaprilat, improves cardiac output during CABG surgery in patients with ischaemic heart dysfunction. Moreover, renal perfusion was better maintained during surgery, and this effect was sustained up to post-operative day 7." ]

[ "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." ]

[ "8569016", "8178840", "11226444", "3828253", "16315025", "2548135", "12627044", "7641897", "8487239", "17217318", "3784917", "10739508", "1532445", "12133397", "8429800", "9459084", "9699198", "7936513", "1961129", "15259280", "8941062", "11729332", "9255748", "10076125", "8892714", "16294460", "10515673", "17108847", "9572210", "11731187", "11727357", "8861084", "16504428", "8746882", "3030392", "8550780", "17626056", "12930575", "10515676", "2971597", "11770191", "7589641", "9141548" ]

[ "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.", "Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group.", "Constant estrogen, intermittent progestogen vs. continuous combined hormone replacement therapy: tolerability and effect on vasomotor symptoms.", "Continuous oestrogen-progestogen treatment and serum lipoproteins in postmenopausal women.", "Effects of two different regimens of continuous hormone replacement therapy on endometrial histopathology and postmenopausal uterine bleeding.", "A prospective 1-year study of estrogen and progestin in postmenopausal women: effects on the endometrium.", "Comparison of the difference in histopathology and cell cycle kinetics among the postmenopausal endometrium treated with different progestins in sequential-combined hormone replacement therapy.", "Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial.", "Evaluation of low-dose estrogen and progestin therapy in postmenopausal women. A double-blind, prospective study of sequential versus continuous therapy.", "Monophasic estrogen-progestogen therapy and sexuality in postmenopausal women.", "Oestrogen-progestogen replacement therapy changes body composition in early post-menopausal women.", "Optimizing continuous-combined hormone replacement therapy for postmenopausal women: a comparison of six different treatment regimens.", "Sequential estrogen and progestogen therapy: assessment of progestational effects on the postmenopausal endometrium.", "[Comparative study on two different dosages of conjugated equine estrogen continuously combined with medroxyprogesterone in prevention of postmenopausal osteoporosis].", "A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment.", "Gonadotropin-releasing hormone analogue plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial.", "Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT.", "Assessment of less than monthly progestin therapy in postmenopausal women given estrogen replacement.", "Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause.", "Endometrial safety and tolerability of triphasic sequential hormone replacement estradiol valerate/medroxyprogesterone acetate therapy regimen.", "Comparison of two continuous combined estrogen progestogen regimens in postmenopausal women: a randomized trial.", "Efficacy of every-other-day administration of conjugated equine estrogen and medroxyprogesterone acetate on gonadotropin-releasing hormone agonists treatment in women with endometriosis.", "Comparison of transvaginal ultrasonography and endometrial biopsy in endometrial surveillance in postmenopausal HRT users.", "Progestational effects of combinations of gestodene on the postmenopausal endometrium during hormone replacement therapy.", "The comparative effect on bone density, endometrium, and lipids of continuous hormones as replacement therapy (CHART study). A randomized controlled trial.", "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.", "Adverse endometrial effects during long cycle hormone replacement therapy. Scandinavian Long Cycle Study Group.", "Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women.", "Bleeding pattern and endometrial changes during continuous combined hormone replacement therapy. The Ogen/Provera Study Group.", "Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: a randomized comparative dose-ranging study.", "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.", "17 beta-estradiol and norethisterone acetate in low doses as continuous combined hormone replacement therapy.", "Results from the Estonian postmenopausal hormone therapy trial [ISRCTN35338757].", "Effects of hormone replacement therapy on growth hormone secretion patterns in correlation to somatometric parameters in healthy postmenopausal women.", "Cyproterone acetate, an alternative progestogen in postmenopausal hormone replacement therapy? Effects on serum lipids and lipoproteins.", "Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women.", "Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women.", "Luteinizing hormone affects uterine receptivity independently of ovarian function.", "Comparison of transdermal estradiol and tibolone for the treatment of oophorectomized women with deep residual endometriosis.", "Efficacy of sequential cyclical hormonal therapy in endometrial cancer and its correlation with steroid hormone receptor status.", "Acceptability and patterns of endometrial bleeding in estradiol-based HRT regimens: a comparative study of cyclical sequential combinations of trimegestone or norethisterone acetate.", "Cardiovascular risk factors and combined estrogen-progestin replacement therapy: a placebo-controlled study with nomegestrol acetate and estradiol.", "Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen-Progestin Interventions Study Investigators." ]

[ "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.", "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.", "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.", "Serum lipids and lipoproteins were examined in 44 healthy postmenopausal women every 3 months during 1 year of treatment with either continuous oestrogen-norethisterone acetate or placebo. Total serum cholesterol and LDL-cholesterol levels were reduced by approximately 15% and 20% (P less than 0.001), respectively in the hormone group but were unchanged in the placebo group. Serum triglycerides levels remained constant in both groups. HDL-cholesterol levels were significantly reduced by approximately 10% in the hormone group but significant reductions of 5-10% also occurred in the placebo group so that differences between the two groups were only significant after 3 months of treatment. Vaginal bleedings were experienced during the first 3 months by eight of the 21 women receiving hormones, but in only one woman after 9 months of therapy. The addition of norethisterone acetate to postmenopausal oestrogen therapy in clinically relevant doses had no adverse effects on lipoproteins as previously reported, even though administered continuously. Moreover, the low frequency of bleeding with continuous oestrogen-progestogen therapy would make this an appropriate alternative in postmenopausal replacement therapy.", "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.", "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 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.", "To determine whether treatment of endometriosis with a GnRH analogue (GnRH-a; goserelin) combined with continuous estrogen and progestogen hormone replacement therapy (HRT) would prevent the hypoestrogenic effects, including loss of bone density, while maintaining efficacy for treatment of endometriosis.\n Randomized controlled trial.\n Fifty premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Score for endometriosis implants equal to four or greater) and significant symptoms of dysmenorrhoea, dyspareunia, and other pelvic pain.\n Patients were randomized to receive either goserelin alone, 3.6 mg SC depot every 4 weeks for 24 weeks, or goserelin, 3.6 mg SC depot every 4 weeks for 24 weeks, plus HRT (25 micrograms transdermal 17 beta E2 daily and 5 mg medroxyprogesterone acetate orally daily) for 20 weeks commencing with the second goserelin injection.\n There was a significant reduction in the extent of pelvic endometriosis in both groups, with no difference between the groups. Both groups experienced an improvement in symptoms and signs, again with no difference between groups. Hypoestrogenic side effects of hot flushes and loss of libido were significantly less in the group that received HRT. The amount of bone mineral density loss was significantly less in the HRT group at the lumbar spine, although it was not prevented completely.\n The addition of HRT to GnRH-a for the treatment of endometriosis did not reduce the efficacy of treatment, and adverse hypoestrogenic effects were decreased, although not abolished.", "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)", "This study aimed to evaluate the effects of monophasic estrogen-progestogen therapy on the sexuality and climacteric symptoms of postmenopausal women.\n A prospective, randomised, double-blind, crossover, placebo-controlled, single-centre study was carried out over a total of 12 consecutive months in 40 postmenopausal women with an intact uterus who had no contraindications to hormone therapy. Patients received 17beta-estradiol 2mg in combination with norethisterone acetate 1mg (Cliane) daily for 6 months or one placebo tablet daily for 6 months. The tablets were identical in appearance. After 6 months, the groups were crossed over and the patients were followed up for another 6 months. The groups were homogenous with respect to age, height, bodyweight, body mass index and race. For the statistical analysis, the group receiving hormone therapy was referred to as group A and the placebo group was designated group B, irrespective of the placebo/hormone therapy sequence.\n In group A there were fewer hot flashes (F=22.85, p<0.01) and an improvement in sexual interest (F=5.55, p<0.05). The sequence in which the medication was received resulted in a statistically significant difference with respect to dyspareunia (F=9.65, p<0.01) and satisfaction with the duration of penetration (F=6.58, p<0.05). In the intrapatient analysis of variation with respect to orgasmic capability and the presence of dialogue with partner regarding the couple's sexual life, whether the placebo was taken prior to or following hormone therapy was significant (F=17.12, p<0.001 and F=7.10, p<0.05, respectively).\n Monophasic estrogen-progestogen therapy has a beneficial effect on sexuality and on hot flashes in postmenopausal women.", "Changes in body composition were investigated in a group of 136 post-menopausal women treated for at least 1 yr with combined oestrogen-progestogen therapy at three different doses, or a placebo. The body composition changes were evaluated using the urinary creatinine excretion rate as an indicator of lean body mass, and the changes in daily creatinine excretion were related to the changes in serum oestradiol and oestrone. The urinary creatinine excretion rate was significantly increased (P less than 0.001) in the group receiving high-dose hormones, and the urinary creatinine/body weight ratio was significantly increased (P less than 0.05) in all treated groups as compared with the placebo-group. The body weight remained unchanged in all groups. The relationships between the changes in daily creatinine excretion and the changes in serum oestradiol and serum oestrone were both significant (P less than 0.05). The present study suggests that high-dose post-menopausal hormone therapy changes the body composition by increasing the muscle mass and that, since the body weight remains unchanged, a proportionate decrease in the fat mass seems to occur.", "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.", "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 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.", "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.", "The aim of this study was to determine whether or not continuous combined HRT used with GnRH-a for the treatment of endometriosis can prevent hypoestrogenic side effects associated with GnRH-a.\n Forty premenopausal women with laparoscopically proven endometriosis entered the study. The patients were randomized into two groups. Group I (n = 19) received 3.75 mg i.m. leuprolide acetate (LA) every 4 weeks for 24 weeks. Group II (n = 21) received 3.7 mg LA combined with 1.25 mg oral conjugated equine estrogen (CEE) and 5 mg oral medroxyprogesterone acetate (MA).\n Total revised AFS score as well as total pelvic pain scores decreased significantly (P < .001) in both groups. However, a statistically significant difference of hot flushes and sweating was reported by women receiving LA + HRT as compared to those treated with LA alone (P < .001). Furthermore, the bone loss at the lumbar spine was 4.2% in group I compared to 0.9% in group II at the end of the study.\n This study suggests that 1.25 mg CEE + 5 mg MA is effective in preventing hypoestrogenic side effects caused by GnRH-a, while the treatment of endometriosis is not impaired.", "To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas.\n In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared.\n Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size.\n The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE-MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE-MPA therapy, at the doses used here, promote fibroid growth.", "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.", "The reduction in cardiovascular risk induced by hormone replacement therapy is only partly explained by changes in serum lipids and lipoproteins. As body composition and body fat distribution in particular are independent predictors of cardiovascular disease, we investigated the effect of postmenopausal hormone therapy on body composition parameters directly measured. Sixty-two early postmenopausal women were followed up for 2 years in a prospective, randomized, placebo-controlled study. We found that combined estrogen-progestogen therapy prevented the increase in abdominal fat after menopause (P less than .05), and that this effect was independent of the effect on serum lipids and lipoproteins. The therapy reduced postmenopausal bone loss significantly (P less than .001), whereas it did not have a statistically significant influence on total body fat mass or total lean body mass. The findings of the present study suggest that some of the protective impact of postmenopausal hormone therapy on cardiovascular disease may be explained by the effect on body composition, in particular abdominal fat.", "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.", "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%).", "We performed a randomized controlled study to determine the efficacy of add-backed therapy by every-other-day administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) on GnRH agonists (GnRH-a) treatment in Japanese women with symptomatic endometriosis. At the end of treatment, serum estrone and estradiol levels in the add-back group (n = 11) were significantly higher than those in the control group (n = 10). The assessment of Beecham classification by bimanual examination, serum CA-125 levels, and the frequency of genital bleeding revealed no significant differences between the two groups. The add-back group showed reduced Kupperman indices relative to those of the control group, and could prevent the loss of bone density. These findings led to a conclusion that GnRH-a therapy added back by every-other-day administration of 0.625 mg CEE and 2.5 mg MPA was a safe and effective treatment for Japanese women with endometriosis.\n Copyright 2001 S. Karger AG, Basel", "To compare transvaginal ultrasonography with histological findings in endometrial evaluation of postmenopausal women using hormone replacement therapy and to evaluate endometrial safety of three hormone replacement therapy regimens.\n In a randomized, comparative study in postmenopausal women, endometrial safety was evaluated using (1) no hormone replacement therapy, (2) oral micronized 17 beta-estradiol/oral sequential dydrogesterone, (3) transdermal 17 beta-estradiol/oral sequential dydrogesterone, or (4) oral tibolone. 85 Non-hysterectomised subjects underwent transvaginal ultrasonography immediately before Pipelle biopsy at baseline and subsequently after 12 and 24 months. Endometrial thickness and uterine dimensions were determined by transvaginal ultrasonography, and endometrial thickness (double-layer) was compared with biopsy results.\n Endometrial evaluation was conveniently performed by transvaginal ultrasonography, and endometrial thickness correlated well with biopsy findings. If endometrial thickness was < 5 mm, the endometrial biopsy sample was either inactive/atrophic or insufficient for histopathological diagnosis. Hyperplastic or malignant changes were not reported. After 24 months, endometrial thickness was increased both in the oral (P < 0.001) and transdermal (P < 0.001) 17 beta-estradiol/dydrogesterone groups, whereas with tibolone the change in endometrial thickness was not different from controls.\n transvaginal ultrasonography of the endometrium reliably predicts the histological picture in hormone replacement therapy users. Using 5 mm endometrial thickness as cut-off point, more than 75% of biopsies could be avoided. All three hormone replacement therapies were safe with respect to the endometrium. With sequential 17 beta-estradiol/dydrogesterone the expected progestogen-induced secretory pattern was observed, whereas endometrial histology under tibolone closely mimicked the natural atrophic postmenopausal state.", "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 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 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.", "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.", "During the past few years serious concern has been raised about the safety of combined estrogen/progestogen hormone therapy, in particular about its effects on the breast. Several observations suggest that androgens may counteract the proliferative effects of estrogen and progestogen in the mammary gland. Thus, we aimed to study the effects of testosterone addition on breast cell proliferation during postmenopausal estrogen/progestogen therapy.\n We conducted a 6-month prospective, randomized, double-blind, placebo-controlled study. A total of 99 postmenopausal women were given continuous combined estradiol 2 mg/norethisterone acetate 1 mg and were equally randomly assigned to receive additional treatment with either a testosterone patch releasing 300 microg/24 hours or a placebo patch. Breast cells were collected by fine needle aspiration biopsy at baseline and after 6 months, and the main outcome measure was the percentage of proliferating breast cells positively stained by the Ki-67/MIB-1 antibody.\n A total of 88 women, 47 receiving active treatment and 41 in the placebo group, completed the study. In the placebo group there was a more than fivefold increase (P<0.001) in total breast cell proliferation from baseline (median 1.1%) to 6 months (median 6.2%). During testosterone addition, no significant increase was recorded (1.6% vs 2.0%). The different effects of the two treatments were apparent in both epithelial and stromal cells.\n Addition of testosterone may counteract breast cell proliferation as induced by estrogen/progestogen therapy in postmenopausal women.", "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 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.", "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 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.", "At present the Women's Health Initiative trial is the only reported randomised controlled trial studying the effects of hormone therapy among healthy postmenopausal women. The Women's Health Initiative reports have been criticized for lacking in generalisability, due to the characteristics of the trial population. We aimed to compare the health effects of oral continuous combined hormone therapy with a placebo and non-treatment among healthy Estonian women.\n Eligible women were randomised into a blind group of hormone therapy versus placebo and into a non-blind group of open label hormone therapy versus non-treatment. One thousand seven hundred and seventy-eight postmenopausal women aged 50-64 at the time of sampling were recruited in 1999-2001 at three clinical centers in Estonia. Participants received conjugated equine oestrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5mg/d, or conjugated equine oestrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 5mg/d, if less than 3 years had passed since menopause at recruitment, or matched placebo or non-treatment. Trial treatment was stopped gradually from 1 January 2004 to 31 May 2004.\n After a follow-up period from 2.0 to 5.0 years the combined hazard ratio, stratified by blinding and adjusted for age at recruitment and former oral contraceptive use was 1.12 (95% confidence interval [CI]: 0.90-1.40) for coronary heart disease, 1.24 (95% CI: 0.85-1.82) for cerebrovascular disease, 1.36 (95% CI: 0.73-2.52) for total cancer, and 0.61 (95% CI: 0.42 to 0.89) for bone fractures.\n The results from the Estonian Postmenopausal Hormone Therapy randomised trial are consistent with the Women's Health Initiative findings.", "The aim of the present study was to investigate the influence of a continuous estrogen, cyclic progesterone replacement therapy on the secretion of growth hormone (GH) and IGF I as well as of somatometric-GH correlation patterns.\n The study included 23 healthy postmenopausal women. Of the proband group 13 randomly selected women were treated with orally applicated 2 mg estradiol-valerat (E2V) and 10 mg dydrogesterone for 10 months. Ten women did not receive any hormonal treatment during this time. After 10 months all probands were reexamined and their GH and IGF I secretion, as well as their somatometric-hormonal correlation patterns, compared with those of a fertile control group.\n It could be shown, that in postmenopausal women a 10-month oral hormone replacement therapy led to a significant increase of GH- and IGF I levels, however, the treated postmenopausal women did not reach the levels of the fertile controls. Those women who did not receive any hormonal treatment and the postmenopausal women before HRT showed nearly identical GH- and IGF I levels as well as somatometric-GH correlation patterns.\n The results of the present paper indicate a marked influence of estrogens on GH and IGF I secretion. Furthermore, hormonal replacement therapy (HRT) may influence somatometric GH correlation patterns too.", "Serum lipids and lipoproteins were studied in 76 healthy postmenopausal women treated for 1 year with either oestradiol valerate sequentially combined with the anti-androgenic progestogen cyproterone acetate (CPA) or placebo. The women were examined every 3 months between days 18 and 21 of the tablet cycle, where the progestogen had been added to the oestrogen for at least 6 days. Combined oestrogen-CPA therapy resulted in significantly reduced levels of total serum cholesterol and LDL-cholesterol at all examinations, but serum triglycerides and HDL-cholesterol levels were similar in the two groups. Total serum cholesterol and LDL-cholesterol were reduced by approximately 5% (P less than 0.01) and 8% (P less than 0.01), respectively, after 1 year of combined oestrogen-CPA therapy in comparison with both the initial values and the placebo group but serum triglycerides and HDL-cholesterol levels were unchanged in both groups.", "The present study was undertaken to determine whether the addition of an androgen to estrogen therapy in postmenopausal women would alter the skeletal response as determined by measurements of markers of bone formation and resorption. Postmenopausal women were treated for 9 weeks with either a combination of 1.25 mg esterified estrogen and 2.5 mg methyltestosterone (E+A) or 1.25 mg conjugated equine estrogen (CEE). Both groups showed a similar decrease in urinary excretion of the bone resorption markers, deoxypyridinoline, pyridinoline, and hydroxyproline. Patients treated with CEE showed decreases in the serum markers of bone formation, bone-specific alkaline phosphatase, osteocalcin, and C-terminal procollagen peptide. In contrast, subjects treated with E+A showed increases in these markers of bone formation. CEE increased, and E+A decreased serum levels of sex hormone-binding globulin as well as triglycerides and high density lipoprotein levels. Only CEE significantly reduced low density lipoproteins. Both regimens were effective in reducing postmenopausal somatic symptoms, but only E+A had a significant effect on psychological symptoms. We conclude that short term administration of androgen with estrogen may reverse the inhibitory effects of estrogen on bone formation. Long term studies are needed to determine the relative benefits and risks of the combination of estrogen and androgen and whether this results in greater increases in bone mass and strength.", "To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy).\n Multicentre, randomised, placebo controlled, double blind trial.\n General practices in UK (384), Australia (91), and New Zealand (24).\n Postmenopausal women aged 50-69 years at randomisation. At early closure of the trial, 56,583 had been screened, 8980 entered run-in, and 5692 (26% of target of 22,300) started treatment.\n Oestrogen only therapy (conjugated equine oestrogens 0.625 mg orally daily) or combined hormone therapy (conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily). Ten years of treatment planned.\n Primary outcomes: major cardiovascular disease, osteoporotic fractures, and breast cancer. Secondary outcomes: other cancers, death from all causes, venous thromboembolism, cerebrovascular disease, dementia, and quality of life.\n The trial was prematurely closed during recruitment, after a median follow-up of 11.9 months (interquartile range 7.1-19.6, total 6498 women years) in those enrolled, after the publication of early results from the women's health initiative study. The mean age of randomised women was 62.8 (SD 4.8) years. When combined hormone therapy (n=2196) was compared with placebo (n=2189), there was a significant increase in the number of major cardiovascular events (7 v 0, P=0.016) and venous thromboembolisms (22 v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60)). There were no statistically significant differences in numbers of breast or other cancers (22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40 v 58, 0.69 (0.46 to 1.03)), and overall deaths (8 v 5, 1.60 (0.52 to 4.89)). Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes revealed no significant differences.\n Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause. The results are consistent with the findings of the women's health initiative study and secondary prevention studies. Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause, when the effect may be different.\n Current Controlled Trials ISRCTN 63718836.", "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.", "To compare the effect of HRT with transdermal estradiol and that of treatment with tibolone in post-menopausal women with residual endometriosis.\n 21 women with residual pelvic endometriosis after bilateral oophorectomy with or without hysterectomy were enrolled in the study and were randomized to HRT with transdermal estradiol 50 mg twice weekly (n = 10) associated with cyclic medroxyprogesterone acetate 10 mg daily in women who preserved uterus, and to treatment with tibolone 2.5 mg administered orally once a day (n = 11). The duration of both treatments was scheduled to last at least 12 months. Residual endometriosis was located in the bowel wall in four patients, in the rectovaginal septum in six and deeply in the retroperitoneal pelvic space in six. All women were symptomatic before oophorectomy.\n All the women were followed for 12 months. No patient suspended therapy because of side effects. Four patients of the estradiol group experienced moderate pelvic pain during treatment compared with only one patient in the tibolone group. One patient in the estradiol group reported severe dyspareunia.\n Although our series is very small, it seems that tibolone may be a safe hormonal treatment for post-menopausal women with residual endometriosis.", "Forty-six eligible women with metastatic endometrial cancer were randomly allocated to receive monthly cycles of either CAF (cyclophosphamide, adriamycin, 5-fluorouracil) or CAF plus Provera 200 mg daily for 3 weeks followed cyclically by Tamoxifen 20 mg daily for 3 weeks. Overall response rates of 15 and 43% were seen with CAF and CAF plus hormonal therapy. Using a multivariate analysis of the results, this difference is significant (P value 0.05). In 8 patients with operable endometrial cancer, negative estrogen receptor concentration (ER less than 15 fmole/mg protein) and Grade 3 disease, the clinical course was aggressive in 4 patients with systemic and local relapse. In 10 other similar patients (negative ER and Grade 3) who received adjuvant cyclical hormonal therapy only 1 relapsed and the other 9 are disease-free for an average of more than 31 months. Sequential cyclical hormonal therapy with ER and progesterone receptor analysis has a place in the management of endometrial carcinoma.", "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 assess the effects of oral E2 replacement therapy combined with nomegestrol acetate, a 19-norprogesterone derivative, on cardiovascular risk factors.\n A double-blind randomized prospective study comparing the effect of a placebo and two oral E2-nomegestrol acetate combinations (1 mg-2.5 mg and 1.5 mg-3.75 mg) over a three-cycle trial.\n Department of Internal Medicine and Nutrition, Hotel-Dieu, Paris, France.\n Fifty-seven nonhysterectomized women with natural menopause.\n Blood pressure, renin substrate, glucose, total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides, apoproteins A1 and B, lipoprotein(a), antithrombin III, fibrinogen, plasminogen, prothrombin fragment 1 + 2, protein C, and total and free protein S.\n Both treatments significantly reduced menopausal complaints, total cholesterol, low-density lipoprotein cholesterol and lipoprotein(a). Treatment with the 1.5 mg-3.75 mg combination resulted in a significant increase in apolipoprotein A1. No significant change were observed in other parameters.\n Sequentially combined with oral E2 in hormone replacement therapy, nomegestrol acetate had favorable effects on plasma lipids and lipoproteins. This nonandrogenic progestin decreased lipoprotein(a) levels as observed previously with medroxyprogesterone acetate combined with conjugated equine estrogens.", "Reports from cross-sectional comparisons, nonrandomized prospective studies, and relatively small clinical trials indicate that postmenopausal hormone therapy may slightly decrease the amount of weight typically gained by women during the decade following menopause. Despite this, widespread belief remains that hormone therapy may cause weight gain. We use data from the Postmenopausal Estrogen/Progestin Interventions trial to characterize the impact of postmenopausal hormone therapy on weight and fat distribution and to examine the consistency of this impact among subgroups of women defined by lifestyle, clinical, and demographic factors. The Postmenopausal Estrogen/Progestin Interventions trial was a 3-yr, placebo-controlled, randomized clinical trial of 875 women assessing the effects on cardiovascular risk factors of four hormone regimens: oral conjugated equine estrogen (CEE) therapy (0.625 mg daily alone), CEE in combination with medroxyprogesterone acetate (2.5 mg daily), CEE in combination with medroxyprogesterone acetate (10 mg daily on days 1-12), and CEE in combination with micronized progesterone (200 mg daily on days 1-12). Women randomly assigned to CEE with or without a progestational agent averaged 1.0 kg less weight gain at the end of 3 yr (P = 0.006) than those assigned to placebo. Assignment to CEE was also associated with averages of 1.2 cm less increase in waist girth (P = 0.01) and 0.3 cm less increase in hip (P = 0.07) girth. In regression models that included weight change as a covariate, none of these differences reached statistical significance. There were no significant differences in weight or girth changes among any of the four active hormone regimens. After accounting for the effects of assignment to active hormone therapy and baseline weight, older age (P 0.008) and higher physical activity level at baseline (P = 0.002) were also independently predictive of less weight gain. The impact of hormone therapy on weight gain was similar among subgroups, except for those defined by baseline smoking status (P = 0.04) and physical activity level at home (P = 0.02). Factors that were independently associated with smaller increases in girths were: for waist, greater overall activity (P = 0.005) and Hispanic ethnicity (P = 0.02); and for hip, work activity (P = 0.003) and greater alcohol consumption (P = 0.03). None of these factors significantly affected the observed overall relationships between estrogen and changes in girth." ]

[ "12510471" ]

[ "Effectiveness of prompted voiding in treating urinary incontinence in cognitively impaired homebound older adults." ]

[ "The objective of this study was to examine the short-term effectiveness of prompted voiding (PV) in cognitively impaired homebound older adults.\n This was a prospective, controlled exploratory study with a cross-over design where usual care controls crossed-over to the intervention following an 8-week observation period.\n Adults aged 60 years and older with urinary incontinence and who met Center for Medicare and Medicaid Services criteria for being homebound were referred to the study by home care nurses from 2 large Medicare-approved home health agencies in a large metropolitan county in southwestern Pennsylvania. Nineteen cognitively impaired older adults were randomly assigned to either the PV intervention or a usual care attention control group.\n Measures used included structured continence and medical histories. Older American Research and Service Physical and Instrumental Activities of Daily Living scales, Folstein Mini Mental State Examination, Clock Drawing Test, Geriatric Depression Scale, Performance-Based Toileting Assessment, bladder diaries, and physical examination.\n Nineteen subjects were randomly assigned to a PV (n = 9) or delayed attention-control group (n = 10). Treatment subjects with complete pretreatment and posttreatment data (n = 6) experienced a mean 60% reduction in daytime incontinent episodes compared with a mean 37% reduction among control subjects (n = 10). Following the control phase, subjects crossed over to the treatment protocol. A total of 15 subjects completed the PV protocol. Among all subjects completing the treatment protocol, there was a 22% reduction in daytime incontinent episodes compared with true baseline (immediately following the control phase for those crossing over from the control group).\n The PV intervention resulted in clinically significant reductions in urinary incontinence for many of the participants, which may be achievable for many cognitively impaired homebound older adults." ]

[ "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." ]

[ "17065044", "21596735", "10485722", "9197872", "16616557", "15695996", "16641396", "19527380" ]

[ "Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status.", "Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial.", "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.", "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.", "Vitamins C and E and the risks of preeclampsia and perinatal complications.", "Comparison of effect of daily versus weekly iron supplementation during pregnancy on lipid peroxidation." ]

[ "To investigate maternal and neonatal outcomes after antioxidant supplementation relatively early in pregnancy (8 to 12 weeks) for pregnant women with low antioxidant status.\n A randomized, double-blind, placebo-controlled trial of daily antioxidant supplementation was performed on pregnant women screening positive for low antioxidant status at 8 to 12 weeks of gestation. Low antioxidant status was defined as a superoxidedismutase (SOD) level below 1102 U/g Hb or 164 U/mL. The supplementation group received the following antioxidants daily: vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 microg), C (200 mg), and E (400 IU), folic acid (400 microg), N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg), Fe (30 mg), calcium (800 mg), and selenium (100 microg). The control group received Fe (30 mg) and folic acid (400 microg). Maternal (preeclampsia, abortion, and hypertension) and perinatal outcomes were assessed.\n In the supplementation group (29 subjects), we observed 2 cases of preeclampsia (6.8%, 1 mild and 1 severe), 1 of IUGR (birth weight 2300 g at 38 weeks), and 1 preterm delivery. In the control group (31 subjects), there were 8 abortions, 9 cases of preeclampsia (29%, 6 mild and 3 severe) with perinatal outcome: 3 preterm delivery cases and 1 IUGR (birth weight 2030 g at 39 weeks). Preeclampsia was significantly less frequent in the supplementation group when compared to the control group (2 vs. 9 cases, p = 0.043, OR = 0.18 [95% CI: 0.03, 0.92]). Finally we focused on the prediction of preeclampsia at 8 to 12 weeks. Combined sensitivity of markers of antioxidant status (SOD slutathione peroxidase, [GPx], and total anti-oxidant status [TAS]) was 33% (false-positive rate of 4.5%).\n Antioxidant supplementation was associated with better maternal and perinatal outcome in pregnant women with low antioxidant status than control supplementation with iron and folate alone. In a selected population already screened positive for low SOD, preeclampsia can be detected in 33% of asymptomatic cases in the first trimester using SOD, GPx, and TAS. It seems feasible that panels of both biochemical and molecular markers may be clinically useful in the prediction of this disease.", "To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk.\n Randomised, blinded, placebo controlled clinical trial.\n Tertiary public hospital in Mexico City.\n Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery.\n Supplementation with a medical food-bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo-during pregnancy.\n Development of pre-eclampsia/eclampsia.\n 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ(2) = 19.41; P < 0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ(2) = 3.76; P = 0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P = 0.004; absolute risk reduction 0.09, 0.05 to 0.14).\n Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846.", "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.", "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.", "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 compare the effect of daily versus weekly iron supplementation on lipid peroxidation, hemoglobin levels and maternal and perinatal outcome in non-anemic pregnant women.\n Of 109 women randomly allocated into three groups, 90 completed the study. Group I (n = 30) received daily iron folic acid; Group II (n = 30) received weekly iron folic acid; Group III (n = 30) received daily iron (III)-hydroxide polymaltose complex. Hemoglobin levels, hematological indices, thiobarbituric acid reactive substances (TBARS) and glutathione levels were measured at baseline (14-16 weeks) and at 30-34 weeks. Statistical analysis was done using the anova test.\n Group I had a highly significant increase in TBARS level (0.61 +/- 0.26 micromol/L, P = 0.000) compared to groups II and III in which the change in TBARS was not significant (0.02 +/- 0.06 and 0.007 +/- 0.06 micromol/L, respectively). There was an insignificant fall in glutathione levels in all groups. There was no significant difference in the mean period of gestation, pregnancy complications and neonatal outcome between the three groups. Among 22.2% of women who were non-compliant, Group I had significantly higher incidence of non-compliance (P = 0.016) and side-effects (P = 0.001). Final hemoglobin was higher in Group I than II (11.9 +/- 1.2, 11.3 +/- 0.9, respectively, P = 0.041). The TBARS level was not statistically different between preterm and term deliveries. Nine out of 11 patients who developed hypertension during pregnancy had preeclampsia. The final TBARS level was significantly higher in these women (P = 0.000).\n Daily supplementation with ferrous sulphate results in greater lipid peroxidation than weekly supplementation, the latter is comparable with daily iron (III)-hydroxide polymaltose complex. Lipid peroxidation levels are significantly higher in preeclampsia." ]

[ "9642605" ]

[ "Antibiotic treatment in preterm labor and intact membranes: a randomized, double-blinded, placebo-controlled trial." ]

[ "Although an association between microbial invasion of amniotic cavity and preterm birth has been extensively demonstrated, there is conflicting evidence regarding the benefits of antibiotic therapy in patients with preterm labor and intact membranes. We attempted to assess the efficacy of amoxicillin and erythromycin on pregnancy outcome in those patients. A randomized, double-blinded, placebo-controlled trial was designed and implemented. A total of 196 patients with singleton pregnancies and preterm labor with intact membranes (22-36 weeks) were randomly allocated to receive either antibiotics or placebo, plus adjunctive parenteral tocolysis, and 173 patients (antibiotics group n = 83 vs. placebo group n = 90) completed the treatment. The overall prevalence of microbial invasion of the amniotic cavity was 5.2% (9/173). No significant difference between both groups was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery, and frequency of clinical chorioamnionitis and endometritis. Rate of cesarean section was significantly higher in the placebo group (28% vs. 12%). Regarding neonatal outcome, no significant difference was detected between both groups in neonatal death, respiratory distress syndrome, proven sepsis, and birthweight. Suspected sepsis was significantly more frequent in the placebo group (6/90 vs. 0/78). The results of this trial indicate that amoxicillin and erythromycin do not prolong pregnancy in patients with preterm labor and intact membranes. A significant reduction in the rate of cesarean section was observed in patients receiving antibiotics. A significant reduction in the rate of neonatal suspected sepsis was also demonstrated." ]

[ "12548322", "48000", "3959016", "8598837", "12521850", "8827572", "9621474", "16880306", "7052115", "7078845", "8781697", "19250367", "3480840", "8605125", "2690305", "8610775", "2698591", "17071427", "2646187", "9184950", "7774736", "7956549" ]

[ "A randomized controlled trial of outpatient versus inpatient labour induction with vaginal controlled-release prostaglandin-E2: effectiveness and satisfaction.", "Elective induction of labour. A randomised prospective trial.", "Induction of labor with an electric breast pump.", "Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group.", "Induction of labour: a comparison of two methods with particular concern to patient acceptability.", "Controlled comparison of induction versus expectant care for prelabor rupture of the membranes at term.", "Induction of labor by intracervical prostaglandin gel and oxytocin infusion in primigravid women with unfavorable cervix.", "Morning compared with evening induction of labor: a nested randomized controlled trial. A nested randomized controlled trial.", "Induction of labour: a comparison of a single prostaglandin E2 vaginal tablet with amniotomy and intravenous oxytocin.", "Role of the cervix in the induction of labor.", "Randomised trial of outpatient induction of labor with vaginal PGE2 at 40-41 weeks of gestation versus expectant management.", "Start of induction of labour with oxytocin in the morning or in the evening. A randomised controlled trial.", "Prostaglandin E2 vaginal suppository for induction of labour: an efficient, safe and popular method.", "Induction of labour: a randomised clinical trial of amniotomy versus amniotomy with oxytocin infusion.", "[Artificial induction of labor at term for medical reasons. Comparison of 2 technics for labor induction, oxytocin + early artificial rupture of the membranes versus prostaglandin E2 vaginal gel. Open randomized controlled study].", "Efficacy of outpatient induction with low-dose intravaginal prostaglandin E2: a randomized, double-blind, placebo-controlled trial.", "Comparison of induced versus non-induced labor in post-term pregnancy. A randomized prospective study.", "Induction of labour at term with vaginal prostaglandins preparations: a randomised controlled trial of Prostin vs Propess.", "Is induction of labor indicated in prolonged pregnancy? Results of a prospective randomised trial.", "A comparative trial of labor induction with misoprostol versus oxytocin.", "Induction of labour at term in primigravidae with low Bishop's score: a comparison of three methods.", "[15-Methyl-PGF2 alpha vaginal suppository for induction of term labor]." ]

[ "Outpatient management in obstetrics is expanding, but evidence to support outpatient labour induction is needed.\n To compare the effectiveness, acceptability, duration of hospitalization, and safety of outpatient and inpatient induction of labour with intravaginal controlled-release prosta-glandin-E2 (CR-PGE2).\n A prospective, randomized, controlled trial enrolled 300 women at term with parity < or = 5 and singleton pregnancies in cephalic presentation. Each had an unscarred uterus, a normal non-stress test (NST), and a Bishop score of < or = 6. After insertion of the CR-PGE2, and 1 hour of monitoring, those in the outpatient group were discharged home, to return with onset of labour or 12 hours later for an NST. If not already in labour 24 hours later, the women returned for inpatient induction. Vaginal examination was not repeated before 24 hours unless the patient was contracting and required analgesia. Inpatients remained on the antepartum ward but were otherwise treated similarly. The women in both groups reported ratings of satisfaction, pain, and anxiety over the telephone until they were in labour.\n There were 150 women randomized to outpatient and 150 women to inpatient induction of labour. The number of women who were in labour or who delivered by 24 hours in the outpatient group was 115 (0.77, 95% confidence interval [CI] 0.70-0.84) and in the inpatient group was 107 (0.72, 95% CI 0.64-0.79). The median times to labour were 9.8 hours (95% CI, 8.1-11.4) and 11.4 hours (95% CI, 10.1-12.7), and to delivery were 21.4 hours (95% CI, 19.2-23.5) and 20.7 hours (95% CI, 18.4-23.0), for the outpatient and inpatient groups, respectively. In the outpatient group, 56% of women reported high satisfaction during the initial 12 hours of induction compared to 39% in the inpatient group (p < 0.008). Ratings of pain and anxiety during the first 12 hours of induction were similar. In the outpatient group, women were at home for a median of 8 hours (95% CI, 6.7-9.4) before labour and delivery. There were no significant differences in adverse outcomes.\n This study suggests that outpatient induction of labour with intravaginal CR-PGE2 may be a reasonable option for selected low-risk women; however, further study is needed to confirm the safety of this approach.", "In a prospective, randomised trial, 111 obstetrically normal pregnant women, who had elective induction of labour performed between 39 and 40 weeks, were compared with 117 controls who were managed expectantly until 41 weeks. Compared with the controls, the patients who had elective induction of labour had significantly less meconium staining in labour and a smaller blood-loss after delivery. The mean length of labour, the amount of pethidine used, and the Apgar scores at 1 minute were similar in the two groups. In the electively induced group, the caesarean-section rate was lower and the use of epidural analgesia more common than in the controls, but the differences were mot statistically signficant. The hour of delivery was similar in the two groups, suggesting that convenience to medical and nursing staff would not be greatly changed by elective induction of labour. There was no evidence that the hazards to mother and child were increased by elective induction, and its use might improve perinatal mortality by reducing the number of unexplained mature stillbirths.", "Nipple stimulation with an electric breast pump was compared with oxytocin infusion as a means of labor induction. The time from stimulation to the onset of regular uterine activity and to 200 Montevideo units of uterine activity and the time until entrance into the active phase of labor were significantly shorter in the nipple stimulation group. Once the women were in active labor, there was no difference between the groups in the length of labor or mode of delivery.", "As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. It is not known whether inducing labor will reduce this risk or whether one method of induction is better then another.\n We studied 5041 women with prelabor rupture of the membranes at term. The women were randomly assigned to induction of labor with intravenous oxytocin; induction of labor with vaginal prostaglandin E2 gel; or expectant management for up to four days, with labor induced with either intravenous oxytocin or vaginal prostaglandin E2 gel if complications developed. The primary outcome was neonatal infection. Secondary outcomes were the need for cesarean section and women's evaluations of their treatment.\n The rates of neonatal infection and cesarean section were not significantly different among the study groups. The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group, 3.0 percent for the induction-with-prostaglandin group, 2.8 percent for the expectant-management (oxytocin) group, and 2.7 percent for the expectant-management (prostaglandin) group. The rates of cesarean section ranged from 9.6 to 10.9 percent. Clinical chorioamnionitis was less likely to develop in the women in the induction-with-oxytocin group than in those in the expectant-management (oxytocin) group (4.0 percent vs. 8.6 percent, P<0.001), as was postpartum fever (1.9 percent vs. 3.6 percent, P=0.008). Women in the induction groups were less likely to say they liked \"nothing\" about their treatment than those in the expectant-management groups.\n In women with prelabor rupture of the membranes at term, induction of labor with oxytocin or prostaglandin E2 and expectant management result in similar rates of neonatal infection and cesarean section. Induction of labor with intravenous oxytocin results in a lower risk of maternal infection than does expectant management. Women view induction of labor more positively than expectant management.", "Induction of labour is a common obstetric intervention. When the cervix is unfavourable ripening agents are used, commonly prostaglandin E2. There are several methods of administration of prostaglandin E2 and little comparative work has been performed as to their acceptability by patients. Patients undergoing induction of labour by prostaglandin E2 were randomised to receive either intravaginal gel or an intravaginal slow-release pessary. Patient satisfaction with the method received was then assessed. Sixty-nine patients were randomised, 34 to receive gel and 35 to receive a pessary. Median scores for satisfaction of the induction process were the same for both methods; however, satisfaction with the labour was increased with those who had been randomised to the pessary group (median pessary=5, gel=4). There may be a marginal improvement in patient satisfaction when a slow-release intravaginal prostaglandin E2 pessary is used for the induction of labour.", "This randomized clinical trial compared oxytocin induction of labor with expectant care for 48 hours after prelabor rupture of the membranes at term. Women at term with prelabor rupture of the membranes for at least 8 hours were assigned at random to induction with oxytocin or to expectant management for 48 hours followed by induction if necessary. Of 168 eligible women, 123 (73%) agreed to participate. More women in the induction group (23%) than in the expectant group (10%) had operative delivery, either cesarean section or instrumental vaginal delivery. In the induction group 41% received analgesia versus 24% in the expectant group (p < 0.005). There was no difference in the rate of maternal and neonatal infection between groups and sepsis was not observed. The active policy of oxytocin induction exposed the mother to a higher risk of operative delivery and a less comfortable labor than the 48 hours expectant care option.", "The rate of Cesarean Section for failed induction of labor and maternal and fetal compilations are high when labor is induced in a nulliparas women with an unripe cervix by amniotomy and oxytocin infusion. Prostaglandins (PG) in different forms have been used for ripening the cervix with an aim of reducing these problems. A prospective randomized trial was performed on one hundred primigravid women between 37 and 42 weeks of gestation with singleton pregnancy, cephalic presentation and unfavorable cervix (Modified Bishop Score < or = 5) in the department of Obstetrics & Gynaecology of Institute of Postgraduate Medicine & Research from 1st May 1996 to 30th April 1997. In this study the efficiency of prostaglandin E2 intracervical (PGE2 IC) gel in induction of labor in a group of primigravid women with unripe cervix was assessed and compared with another group with similar characteristics using oxytocin infusion and artificial rupture of membrane (ARM). The Modified Bishop Score (MBS), interval between IOL and onset of labor and the duration of labor after insertion of PGE2 gel was significantly different from those of oxytocin infusion group. But the Apgar Score at 1 & 5 min had shown no statistically significant difference. Any significant difference could also not be detected in the mode of delivery between the two induction group. The proportion of emergency Cesarean Section (CS) was high in the oxytocin infusion group than that of in the prostaglandin group. There was also no significant difference regarding the acceptability of both the induction methods.", "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.", "In a randomized controlled study of 100 women of low parity and favourable induction features, induction of labour by means of a single vaginal tablet containing 3 mg of prostaglandin E2 (PGE2) was compared with the conventional method of amniotomy and intravenous oxytocin. Four of the patients (8%) who received the prostaglandin tablet required additional intravenous oxytocin to achieve delivery. The prostaglandin group had a longer mean overall induction-delivery interval but a shorter amniotomy-delivery interval than the oxytocin group. One patient in the PGE2 group and two in the oxytocin group required caesarean section. The PGE2 treated patients expressed a higher level of satisfaction with their method of induction, they required less analgesia, had less blood loss at delivery and their babies had a lower incidence of neonatal jaundice.", "A study on induction of labor was carried out to test the hypothesis that changing the cervix will enhance the effectiveness of induction of labor. Fifty pregnant women near term with Bishop scores of 4 or less were divided into 5 study groups, in which a 12-hour preparation phase procedure was carried out to produce cervical or myometrial changes. All women had continuous measurement of uterine activity by an extraovular catheter. The patients were divided into 1) control subjects, and into groups treated with 2) laminaria, 3) Foley catheter, 4) amniotomy, and 5) oxytocin infusion. These preparation techniques were used for 12 hours, after which rupture of membranes was carried out in all cases. Although all procedures significantly changed the cervix, none but oxytocin affected the induction-to-delivery interval. The authors concluded that when a study design rigidly controls for cervical Bishop score, timing of rupture of membranes, and oxytocin infusion rates, the cervical preparation alone will not enhance inducibility.", "Two hundred consecutive women with uncomplicated pregnancies, at or within 4 days of their expected date of confinement, were prospectively randomized into 2 groups. One group had expectant management, with twice weekly surveillance tests, while the other group had 3 mg of vaginal prostaglandin E2 as outpatient treatment. There were 104 women in the expectant group and 70 in the induction group (26 women allocated to induction preferred no treatment). The average number of days to delivery was 1.6 in the induction group and 5.2 in the expectant group (p < 0.001). While meconium was much less frequent in the induction group (p < 0.002), all other outcome measures, including cesarean section rates, incidence of macrosomia, and Apgar scores, were similar in the two groups.", "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.", "Two different methods for induction of labour were randomly used in 100 women with a favourable cervix. The patients were treated with either prostaglandin vaginal suppositories containing 2.5 mg PGE2 in a base of Witepsol S55 (Dynamit Nobel) or intravenous infusion of oxytocin. The PGE2 vaginal suppository was significantly more efficient than the intravenous infusion of oxytocin in relation to the time interval from the start of induction of labour to delivery. Also the percentage of women who delivered within 48 hours (success rate) was higher in the suppository group. Significantly more women in the suppository group found this induction method recommendable.", "To compare two methods of induction of labour-amniotomy with oxytocin infusion versus amniotomy alone.\n Prospective randomised clinical trial.\n The department of obstetrics in a Swedish central hospital.\n One hundred and ninety-six pregnant women with indication for induction of labour at term and a favourable cervix (modified Bishop score > or = 6).\n The women were randomised to amniotomy followed by oxytocin infusion after 1 h (group A, n = 98) or amniotomy alone (group B, n = 98). If labour had not ensued on the following morning, after approximately 24 h, the women in group B were given an oxytocin infusion.\n Induction-delivery interval, duration of labour, time spent in delivery ward, oxytocin use, maternal and neonatal clinical outcome.\n Amniotomy combined with early oxytocin infusion resulted in shorter induction-delivery interval (median 6.0 h; 95% confidence interval (CI) 5.0 to 6.5 h) than amniotomy alone (median 9.0 h; 95% CI 7.5 to 10.0 h). This was due to a shorter latent period in the former group (median 2.3 h; 95% CI 2.0 to 3.0 h) compared to the latter (median 4.3 h; 95% CI 3.0 to 5.5 h). The duration of labour stages 1 and 2 were similar in both groups. The time spent in the delivery ward was slightly reduced for women managed by amniotomy alone (median 5.0 h; 95% CI 4.5 to 6.0 h) compared with those managed by the combination of amniotomy and oxytocin infusion (median 6.0 h; 95% CI 5.0 to 6.5 h). Eighty-seven percent in group A and 32% in group B were given oxytocin, and the total oxytocin infusion time was nearly five times longer in group A. No other important effect on maternal or fetal outcomes was demonstrated.\n With regard to safety the results do not warrant recommending either type of labour induction. The minor differences observed between the induction groups justify an individual management policy, with attention paid to both the indication for induction of labour and the woman's choice.", "Labor induction for medical reasons is a situation rather well-controlled by the combination: \"oxytocin-amniotomy\" when the cervix is favorably open. However, new induction techniques are currently under study, especially vaginal administration of PGE2 which presents the advantage of being simple to administer and better accepted by the patients. This study compared the classical technique, oxytocin perfusion and early artificial rupture of the membranes, with the vaginal administration of PGE2 gel (first dose: 1 mg, second dose 1 or 2 mg, six hours later). The success rate of both techniques is comparable, approximately 70 p. cent. Also, the times between amniotomy and delivery are identical, approximately 5 hours. On the contrary, the lapses of time between the onset of the induction and the delivery, vary significantly, being always longer in the PGE2 group. However, the dose of vaginal PGE2 gel as well as the time of artificial membrane rupture could be modified in order to decrease the delay of the effect.", "Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor.\n A randomized, double-blind, placebo-controlled trial was performed with 100 low-risk patients having well-dated pregnancies. Women with a Bishop score < or = 6 at 38 to 40 weeks' gestation were administered either 2 mg of intravaginal prostaglandin E2 gel or placebo for 5 consecutive days as outpatients while undergoing fetal monitoring.\n The median interval from randomization to delivery was 4 days in the prostaglandin E2 group (range 0 to 28 days) versus 10 days in the placebo group (range 0 to 26 days, p = 0.002). Twenty-seven of 50 patients (54%) in the prostaglandin E2 group were admitted for labor during the dosing interval compared with 10 placebo-treated patients (20%, p = 0.001). The mean gestational age at delivery was significantly reduced in the treatment group (39.9 +/- 1.0 weeks vs 40.5 +/- 0.99 weeks, p = 0.003) as was the incidence of postdates pregnancy (40% vs 66%, p = 0.016). Hyperstimulation was observed in one prostaglandin E2-treated patient, but no intervention was required.\n Outpatient low-dose prostaglandin E2 gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring.", "To determine the proper management of pregnancy in uncomplicated cases going beyond 42 weeks.\n Randomized controlled trial of induction of labor at or shortly after the 42-week limit, versus close monitoring without induction except when indicated for medical reasons.\n Hospital's obstetrical department\n 188 pregnant women, randomly allocated to two groups with 94 in each.\n Induction of labor by stripping of membranes and i.v. oxytocin infusion, with artificial rupture of membranes when the cervical opening was 3 cm or more in diameter. The control group was followed with clinical, biochemical and electronic tests, intervention being applied according to needs.\n Frequency and modes of operative delivery, maternal and perinatal morbidity and mortality.\n The distribution of gestational age (in weeks) at birth was almost identical in the two groups, but there were more operative deliveries in the control group than in the induction group (64 versus 48, p less than 0.05). Maternal complications and perinatal morbidity rates were equally distributed between the groups. There was one perinatal death in the induction group and two deaths among the controls.\n With due reservation for small numbers, routine induction after term may result in fewer operative deliveries. No other advantage has been demonstrated when compared with close monitoring and intervention when medically indicated.", "The purpose of the trial was to determine whether a sustained release preparation of prostaglandin E2 (Propess) is better in inducing labour when compared with the more widely used short-acting (instant-release) preparation (Prostin). A randomised controlled clinical trial involving 100 pregnant women at term with an indication for induction of labour was conducted in a district general hospital in the UK over a 1-year period. Women were randomised to receive one of the two preparations. The study revealed that there was no statistically significant difference in time to onset of labour, duration of labour, total time from induction to delivery, method of delivery, and analgesia requirements. The number of preparations required to induce labour were significantly less in the Propess group. Our data suggest that both Propess and Prostin are safe and effective in induction of labour, for either primips or multips. However, Prostin use is more cost-effective.", "In 345 women with a favorable cervical score at due date, labor was either induced by means of intravaginal application of tablets containing 3 mg of prostaglandin E2 or spontaneous onset of labor was awaited until the 42nd week of pregnancy. Eighty percent of the nulliparae and 96.3% of the multiparae of the induction group gave birth within 24 h of the administration of the first tablet. All pertinent delivery intervals were significantly shorter in this group compared to those women where spontaneous onset of labor was awaited. The rate of operative deliveries was lower in the induction group. With the exception of 1 fetal death 3 days after due date, fetal outcome was excellent in both groups. Elective induction was at least equivalent to awaiting the onset of spontaneous labor and was not associated with higher complication rates due to the method of induction.", "To determine the efficacy and safety of intravaginal misoprostol compared with intravenous oxytocin in cervical ripening and labor induction.\n The study was carried out at the Department of Obstetrics and Gynecology at the Hospital Loayza, Lima, Peru. The sample included 123 pregnant women with any indication for labor induction. The study was prospective and randomized. We compared the effect of 50 micrograms of intravaginal misoprostol administered every 4 h up to 600 micrograms with that observed using the standard protocol of oxytocin by continuous infusion.\n 57 patients with misoprostol (group 1) and 63 with oxytocin (group 2) were enrolled. Delivery occurred in 45 patients (78.9%) in group 1 and in 37 (58.7%) in group 2 (P < 0.017). Complications including tachysystole, uterine hypertony and hyperstimulation were higher in group 1, 21.1% than in group 2, 7.9% (P < 0.04). The incidence of cesarean section in both groups was similar to the overall incidence in our center. No differences were observed between groups in perinatal and postpartum adverse outcomes. The interval from start of induction to vaginal delivery was significantly shorter in the oxytocin group (8.4 +/- 4.1 vs. 11.3 +/- 6.9 h, P < 0.005).\n Intravaginal administration of misoprostol is a safe and effective alternative for cervical ripening and labor induction. Maternal and neonatal complications did not increase significantly.", "To determine which of three methods of induction of labour at term in primigravidae with a low Bishop's score is effective and safe.\n Random allocation to Prostin E2 and amniotomy later (Group A); low amniotomy and oxytocin titration (Group B); and intra-cervical Foley balloon overnight followed next morning by low amniotomy and oxytocin titration (Group C).\n Primigravidae (n = 90) in the University Hospitals, Benin City, Nigeria.\n (i) Time taken to achieve 3 uterine contractions in 10 min; (ii) induction-delivery interval.\n The mean time interval between intervention and regular uterine contractions was shortest in Group C (A vs. C, P < 0.02; A vs. B, P < 0.02). The mean induction-delivery interval was shortest in Group C (11.1 h) followed by Group B (13.9 h) and Group C (17.9 h) P < 0.05-0.001.\n The induction-delivery interval was shortest when using a Foley catheter for cervical ripening followed by amniotomy and oxytocin titration.", "The results of intravaginal 15-methyl PGF2 alpha (PG05) were compared with gemeprost (ONO-802, PGE1 analogue) pessary and oxytocin intravenous infusion for induction of labor at term. A total of 99 primipara with singleton pregnancy and cephalic presentation, accepted for induction, was randomly allocated into 3 groups: group 1, PG05 0.25 mg (n = 33), group 2, ONO-802 0.125 mg (n = 33), and group 3, oxytocin i.v. (n = 33). Among these, 30 cases had plasma PGs (PGE2 and PGF2 alpha) concentration determined before and after induction. Successful treatment was defined as active labor starting within 24 hours following induction or an increase of cervical Bishop score > 3. The success rates were not significantly different among the 3 groups (PG05 88%, ONO-802 100%, and oxytocin 79%), (P > 0.05). No significant difference existed in the plasma prostaglandin concentrations as well. It is suggested that PG05 may be used for induction of labor at term." ]

[ "9512207", "2052460", "2181103" ]

[ "Randomized, controlled, blinded trial of doxapram for extubation of the very low birthweight infant.", "[A comparison of the efficacy of aminophylline and doxapram in preventing idiopathic apnea in preterm newborn infants].", "A blinded, randomized, placebo-controlled trial to compare theophylline and doxapram for the treatment of apnea of prematurity." ]

[ "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.", "Doxapram is an analeptic of the respiratory system that has been used in the last few years for the treatment of idiopathic apnea spells in infants who show resistance to methylxantine. In this study we have compared the efficacy of aminophylline and doxapram for the prevention of idiopathic apnea spells in two groups of preterm infants comparable for gestational age, birthweight and postnatal age. The two drugs resulted to be effective in preventing the spells of apnea in 66% and 60% of the cases respectively. In the cases in which there was a partial or negative response, the association of the two substances resulted in a noticeable reduction of the apnea spells. The positive effect of the association of aminophylline and doxapram is probably due to the different action mechanism on the stimulation of the respiratory system.", "A blinded, randomized, placebo-controlled trial was conducted to evaluate the effectiveness of theophylline and doxapram therapy in 31 infants with significant apnea of prematurity. Of 10 infants, two had a short-term response to placebo, 8 of 10 infants to theophylline, and 7 of 11 infants to doxapram (placebo vs treatment with theophylline or doxapram: p = 0.01). The two infants who initially responded to placebo remained responsive for the duration of the study. Of the eight infants in whom treatment with placebo failed, five were randomly assigned to receive theophylline, for a total of 15 infants treated with theophylline, and two of the eight were randomly assigned to receive doxapram, for a total of 13 infants treated with doxapram; the remaining infant required tracheal intubation. Of the 15 infants randomly assigned to receive theophylline, seven responded for the duration of the study; of the eight infants who did not respond to treatment with theophylline, five responded to doxapram, one responded to a combination of theophylline and doxapram, and two remained resistant to treatment. Of the 13 infants randomly assigned to receive doxapram four responded for the duration of the study; of the nine who did not respond to doxapram, seven responded to theophylline, one responded to a combination of theophylline and doxapram, and one remained resistant to treatment. This study demonstrates that although therapy with theophylline or doxapram is associated with a significant short-term reduction in the incidence of apnea compared with that in placebo-treated infants, the long-term response to treatment is frequently incomplete and is not sustained more than 1 week." ]

[ "19543080", "19433778", "490882", "17635851", "19142758", "16147905", "16148616", "12874091", "12517683", "12360162", "2096204", "10212327", "15609886", "9469797", "7795830", "12045644", "11849464", "2861311", "16647628", "1330398" ]

[ "Reduction of morning blood pressure surge after treatment with nifedipine GITS at bedtime, but not upon awakening, in essential hypertension.", "Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: improved blood pressure control with bedtime dosing.", "Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group.", "Comparison of the efficacy of morning versus evening administration of telmisartan in essential hypertension.", "Administration-time-dependent effects of olmesartan on the ambulatory blood pressure of essential hypertension patients.", "Administration time-dependent effects of valsartan on ambulatory blood pressure in elderly hypertensive subjects.", "Treatment of non-dipper hypertension with bedtime administration of valsartan.", "Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects.", "Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension.", "Preventing increases in early-morning blood pressure, heart rate, and the rate-pressure product with controlled onset extended release verapamil at bedtime versus enalapril, losartan, and placebo on arising.", "Placebo effect and adaptation to noninvasive monitoring of BP.", "Morning versus evening amlodipine treatment: effect on circadian blood pressure profile in essential hypertensive patients.", "Resistant arterial hypertension and hyperlipidemia: atorvastatin, not vitamin C, for blood pressure control.", "The effect on 24 h blood pressure control of an angiotensin converting enzyme inhibitor (perindopril) administered in the morning or at night.", "Trial of Nonpharmacologic Intervention in the Elderly (TONE). Design and rationale of a blood pressure control trial.", "Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality.", "Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes.", "Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial.", "Pharmaceutical care program for patients with uncontrolled hypertension. Report of a double-blind clinical trial with ambulatory blood pressure monitoring.", "Effect of timing of administration on the plasma ACE inhibitory activity and the antihypertensive effect of quinapril." ]

[ "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.", "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 Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with \"mild\" hypertension.", "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.", "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 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 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.", "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.", "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.", "Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early-morning period, a time when both morbid and mortal cardiovascular events are increased compared with other times of the day.\n We studied the effects of a chronotherapeutic delivery system of verapamil (controlled-onset extended release [COER]-24 system) dosed at bedtime versus conventional morning administration of both enalapril and losartan on the blood pressure (BP), heart rate, and the heart rate systolic BP product during the first 4 hours after awakening in a placebo-controlled, forced-titration trial. There were 357 men and women enrolled in the trial with an untreated sitting diastolic BP of 95 to 114 mm Hg and ambulatory daytime diastolic BP > or =85 mm Hg. Patients were randomized to either COER-verapamil hydrochloride each evening (240 mg titrated to 360 mg), enalapril each morning (10 mg titrated to 20 mg), losartan each morning (50 mg titrated to 100 mg), or placebo. Early morning assessments of BP, heart rate, and the heart rate systolic BP product were performed by use of 24-hour ambulatory recordings after 4 weeks (low dose) and 8 weeks (high dose) of therapy.\n Results were similar at weeks 4 and 8 for all treatment groups except that the magnitude of change was greater at week 8. After 8 weeks of treatment, reductions in early morning BP by COER-verapamil were significantly greater (-15/-10 mm Hg) than enalapril (-9/-7 mm Hg, P <.01) and losartan (-8/-5 mm Hg, P <.001). COER-verapamil also led to greater reductions in morning heart rate, the rate-pressure product, and the rate-of-rise of BP compared with the other 2 active treatment groups. Reductions in mean 24-hour BP were greater in patients treated with COER-verapamil compared with placebo and losartan, and similar to reductions in patients treated with enalapril.\n Bedtime administration of an agent designed to parallel the circadian rhythm of BP and heart rate led to significantly greater early morning hemodynamic effects compared with other conventional once-daily antihypertensive agents dosed in the morning.", "Three 24 h ambulatory monitorings of BP were performed at two-week intervals in 21 untreated hypertensives (mean age 38 +/- 10 yrs, 13 males and 9 females). After the first baseline monitoring, the patients were randomised, according to a cross-over design, to one of the following sequences: no therapy to placebo or placebo to no therapy. At the end of each period, noninvasive ambulatory monitoring was performed. Mean +/- SE 24 h systolic (SBP) and diastolic (DBP) pressures recorded at the first monitoring were 129.2 +/- 3.5 mmHg and 81.7 +/- 2.3 mmHg respectively. At the second and third monitorings, mean 24 h BP differences versus baseline levels were -2.9 +/- 1.8 and -4.7 +/- 1.7 mmHg for SBP, and -2.0 +/- 1.1 and -2.7 +/- 1.5 mmHg for DBP. Both SBP and DBP differences at repeated monitorings were significant by analysis of variance (P less than 0.05). No significant effects on BP of treatment sequence or of placebo administration were found. Analysis of covariance showed a significant relationship between initial 24 h BP and subsequent mean 24 h BP differences (SBP: beta = -0.260, DBP: beta = -0.124). ANOVA performed on waking and sleeping BP separately showed the observed differences to be significant only during waking hours. Regression analysis showed that the decrease in 24 h BP at repeated monitorings was significantly related to the extent of 'white coat'-induced BP increase only for DBP (P = 0.022). For both 24 h SBP and DBP, however, a negative correlation between the alarm reaction to the presence of the physician and 24 h BP decrease at repeated monitorings was observed. It is concluded that noninvasive ambulatory monitoring is subject to adaptative phenomena but not to placebo effect. Factors influencing the defence reactions to manual measurements and to ambulatory monitoring might be partly different.", "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.", "Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP goals.\n To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.\n Forty-eight hyperlipidemic subjects with RH (office systolic BP >140 mmHg and/or office diastolic BP >90 mmHg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17)--mean 24 hour SBP 150.6 +/- 5.2 mmHg, DBP 86.1 +/- 3.3 mmHg, low density lipoprotein 158.1 +/- 24.5 mg/dl--received vitamin C 500 mg per day; Group ATR (n = 15)--mean 24 hour SBP 153.1 +/- 4.8 mmHg, DBP 87.1 +/- 6.7 mmHg, LDL 162.6 +/- 13.6 mg/dl--received atorvastatin 20 mg/day; and Group PLA (n = 16)--mean 24 hour SBP 151.1 +/- 7.4 mmHg, DBP 84.8 +/- 5.9 mmHg, LDL 156.7 +/- 26.1 mg/dl--received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.\n In the ATR group there were significant reductions of SBP (deltaSBP1-2: 13.7 +/- 5.6 mmHg, P 0.001), DBP (deltaDBP1-2: 7.8 +/- 5.7 mmHg, P 0.01), LDL (deltaLDL1-2: 67.7 +/- 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD (deltaFMD2-1: 4.2 +/- 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.\n In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.", "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.", "National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure (BP). However, data to support such recommendations in older persons are virtually nonexistent. The Trials of Nonpharmacologic Intervention in the Elderly (TONE) is a randomized, controlled trial that will test whether weight loss or a reduced sodium (Na) intake or both can maintain satisfactory BP control, without unacceptable side effects, after withdrawal of antihypertensive drug therapy. Medication-treated hypertensives (aged 60 to 80 years) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are randomly assigned to one of four groups: (1) weight loss alone, (2) reduced Na intake alone, (3) combined weight loss and reduced Na intake, or (4) usual life-style (control group). Overweight participants are randomized to one of these four groups, while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group. The interventions, tailored to the needs of older persons, use behavioral approaches to accomplish intervention-specific goals (weight loss > or = 10 lb, daily Na intake < or = 80 mEqa). Three months after the start of intervention, antihypertensive drug therapy is withdrawn. The primary trial end point is a BP of 150/90 mm Hg or higher, resumption of antihypertensive drug therapy, or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up. It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy.", "Traditional fluid resuscitation strategy in the actively hemorrhaging trauma patient emphasizes maintenance of a normal systolic blood pressure (SBP). One human trial has demonstrated improved survival when fluid resuscitation is restricted, whereas numerous laboratory studies have reported improved survival when resuscitation is directed to a lower than normal pressure. We hypothesized that fluid resuscitation titrated to a lower than normal SBP during the period of active hemorrhage would improve survival in trauma patients presenting to the hospital in hemorrhagic shock.\n Patients presenting in hemorrhagic shock were randomized to one of two fluid resuscitation protocols: target SBP > 100 mm Hg (conventional) or target SBP of 70 mm Hg (low). Fluid therapy was titrated to this endpoint until definitive hemostasis was achieved. In-hospital mortality, injury severity, and probability of survival were determined for each patient.\n One hundred ten patients were enrolled over 20 months, 55 in each group. The study cohort had a mean age of 31 years, and consisted of 79% male patients and 51% penetrating trauma victims. There was a significant difference in SBP observed during the study period (114 mm Hg vs. 100 mm Hg, p < 0.001). Injury Severity Score (19.65 +/- 11.8 vs. 23.64 +/- 13.8, p = 0.11) and the duration of active hemorrhage (2.97 +/- 1.75 hours vs. 2.57 +/- 1.46 hours, p = 0.20) were not different between groups. Overall survival was 92.7%, with four deaths in each group.\n Titration of initial fluid therapy to a lower than normal SBP during active hemorrhage did not affect mortality in this study. Reasons for the decreased overall mortality and the lack of differentiation between groups likely include improvements in diagnostic and therapeutic technology, the heterogeneous nature of human traumatic injuries, and the imprecision of SBP as a marker for tissue oxygen delivery.", "Although several important studies have been performed in hypertensive type 2 diabetic patients, it is not known whether lowering blood pressure in normotensive (BP <140/90 mm Hg) patients offers any beneficial results on vascular complications. The current study evaluated the effect of intensive versus moderate diastolic blood pressure (DBP) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients.\n The current study was a prospective, randomized controlled trial in normotensive type 2 diabetic subjects. The subjects were randomized to intensive (10 mm Hg below the baseline DBP) versus moderate (80 to 89 mm Hg) DBP control. Patients in the moderate therapy group were given placebo, while the patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication. The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion, progression of retinopathy and neuropathy and the incidence of cardiovascular disease.\n The mean follow-up was 5.3 years. Mean BP in the intensive group was 128 +/- 0.8/75 +/- 0.3 mm Hg versus 137 +/- 0.7/81 +/- 0.3 mm Hg in the moderate group, P < 0.0001. Although no difference was demonstrated in creatinine clearance (P = 0.43), a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria (P = 0.012) and microalbuminuria to overt albuminuria (P = 0.028). The intensive BP control group also demonstrated less progression of diabetic retinopathy (P = 0.019) and a lower incidence of strokes (P = 0.03). The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent.\n Over a five-year follow-up period, intensive (approximately 128/75 mm Hg) BP control in normotensive type 2 diabetic patients: (1) slowed the progression to incipient and overt diabetic nephropathy; (2) decreased the progression of diabetic retinopathy; and (3) diminished the incidence of stroke.", "A double-blind randomised placebo-controlled trial of antihypertensive treatment was conducted in patients over the age of 60. Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90-119 mm Hg and a systolic pressure in the range 160-239 mm Hg. 840 patients were randomised either to active treatment (hydrochlorothiazide + triamterene) or to matching placebo. If the blood pressure remained raised, methyldopa was added to the active regimen and matching placebo in the placebo group. An overall intention-to-treat analysis, combining the double-blind part of the trial and all subsequent follow-up, revealed a non-significant change in total mortality rate (-9%, p = 0.41) but a significant reduction in cardiovascular mortality rate (-27%, p = 0.037). The latter was due to a reduction in cardiac mortality (-38%, p = 0.036) and a non-significant decrease in cerebrovascular mortality (-32%, p = 0.16). In the double-blind part of the trial, total mortality rate was not significantly reduced (-26%, p = 0.077). Cardiovascular mortality was reduced in the actively treated group (-38%, p = 0.023), owing to a reduction in cardiac deaths (-47%, p = 0.048) and a non-significant decrease in cerebrovascular mortality (-43%, p = 0.15). Deaths from myocardial infarction were reduced (-60%, p = 0.043). Study-terminating morbid cardiovascular events were significantly reduced by active treatment (-60%, p = 0.0064). Non-terminating cerebrovascular events were reduced (-52%, p = 0.026), but the non-terminating cardiac events were not (+3%, p = 0.98). In the patients randomised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial.", "Pharmaceutical care programs may be an option to improve blood pressure (BP) control in patients with uncontrolled hypertension. The aim of this study was to evaluate the efficacy of pharmaceutical care programs in treating patients with resistant hypertension.\n In a double-blind randomized clinical trial, 71 patients with uncontrolled BP were enrolled in a pharmaceutical care program or in a control group and underwent a series of cognitive tests. The primary outcome was change in ambulatory BP (ABP) between the baseline evaluation and the final visit 6 months later. The secondary outcomes were the frequency of drug-related problems and adherence as determined by plasma levels of hydrochlorothiazide.\n The delta-values between the intervention and control groups for ABP in the different daily periods, with the corresponding 95% confidence limits, adjusted for age and baseline BP were: 3 (-1 to 5), 2 (-2 to 4), and 5 (-1 to 6) mm Hg for 24 h, daily and nightly systolic BP, respectively. The corresponding values for diastolic BP were 1 (-1 to 3), 0 (-2 to 2), and 3 (-1 to 4) mm Hg, respectively. Hydrochlorothiazide was detected in the plasma in 21 of 27 patients in the intervention group that attended to all appointments and 24 of 30 patients in the control group (P = .904).\n The pharmaceutical care program tested in this trial was feasible and showed a trend for better BP control in patients with uncontrolled hypertension.", "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." ]

[ "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." ]

[ "3351998", "1592640", "20360500", "12142826", "11514765", "16721238", "17049347", "12579017", "11514766" ]

[ "A comparison of nail-plate fixation and Ender's nailing in pertrochanteric fractures.", "[The gamma-nail as a resilient alternative to the dynamic hip screw in unstable proximal femoral fractures in the elderly].", "A comparison of the long gamma nail with the sliding hip screw for the treatment of AO/OTA 31-A2 fractures of the proximal part of the femur: a prospective randomized trial.", "Pertrochanteric fractures: is there an advantage to an intramedullary nail?: a randomized, prospective study of 206 patients comparing the dynamic hip screw and proximal femoral nail.", "Prospective randomized controlled trial of an intramedullary nail versus dynamic screw and plate for intertrochanteric fractures of the femur.", "Cephalomedullary nails in the treatment of high-energy proximal femur fractures in young patients: a prospective, randomized comparison of trochanteric versus piriformis fossa entry portal.", "One and two femoral neck screws with intramedullary nails for unstable trochanteric fractures of femur in the elderly--randomised clinical trial.", "Slotted intramedullary hip screw nails reduce proximal mechanical unloading.", "Prospective randomized comparison between a dynamic hip screw and a mini-invasive static nail in fractures of the trochanteric area: preliminary results." ]

[ "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.", "In a prospective randomised trial between September 1989 and June 1990 one hundred patients with per- and subtrochanteric fractures were consecutively treated by gamma-nail or DHS. The average age of both groups was about 80 years. The operation time for gamma-nailing was longer than for DHS implantation and also the postoperative blood loss was higher in the gamma-nail group. We found no difference of intraoperative blood loss, of perioperative lethality and in duration of hospital care. 90% of gamma-nail patients and 80% of DHS patients were successfully able to walk four days after operation with full weight bearing on the operated limb. Three patients in the DHS group with unstable fractures got cranial perforation of the cephalic screw mobilisation. Five patients of the gamma-nail group were reoperated, one case because of missed distal locking, one because of cranial perforation of the cephalic screw after varus dislocation of the proximal fragment. One patient suffered intraoperatively a proximal femur shaft fracture which was corrected during operation. In one case a wound hematoma was evacuated, an other patient needed secondary wound closure. Despite technical imperfection of implant and instruments, we conclude that the gamma-nail allows a very high percentage early and full weight bearing immediately after operation. So we consider that in the treatment of unstable pertrochanteric fractures of geriatric patients, the gamma-nail has proven to be more efficient than the DHS.", "Controversy exists with regard to whether to treat AO/OTA 31-A2 fractures of the proximal part of the femur with an intramedullary device or an extramedullary device. A prospective, randomized, controlled trial was performed to compare the outcome of treatment of these unstable fractures of the proximal part of the femur with either a sliding hip screw or a long gamma nail.\n Two hundred and ten patients presenting with an AO/OTA 31-A2 fracture of the proximal part of the femur were randomized, at the time of admission, to fixation with use of either a long gamma nail or a sliding hip screw. The primary outcome measure was reoperation within the first postoperative year. Secondary measures included mortality, length of hospital stay, transfusion rate, change in mobility and residence, and quality of life as measured with the EuroQol 5D outcome score.\n There was no significant difference between the reoperation rates for the two groups. In total, five patients (three from the long-gamma-nail group and two from the sliding-hip-screw group) underwent revision surgery because of cut-out. Tip-apex distance was found to correlate with the implant cut-out rate. There was no significant difference between the two groups in terms of the EuroQol 5D outcome scores, the mortality rates after correction for the mini-mental score, or any of the secondary outcome measures.\n When compared with the long gamma nail, the sliding hip screw should remain the gold standard for the treatment of AO/OTA 31-A2 fractures of the proximal part of the femur because it is associated with similar outcomes with less expense.", "To compare the results between a sliding compression hip screw and an intramedullary nail in the treatment of pertrochanteric fractures.\n Prospective computer-generated randomization of 206 patients into two study groups: those treated by sliding compression hip screw (Group 1; n = 106) and those treated by intramedullary nailing (Group 2; n = 100).\n University Level I trauma center.\n All patients over the age of fifty-five years presenting with fractures of the trochanteric region caused by a low-energy injury, classified as AO/OTA Type 31-A1 and A2.\n Treatment with a sliding compression hip screw (Dynamic Hip Screw; Synthes-Stratec, Oberdorf, Switzerland) or an intramedullary nail (Proximal Femoral Nail; Synthes-Stratec, Oberdorf, Switzerland).\n Intraoperative: operative and fluoroscopy times, the difficulty of the operation, intraoperative complications, and blood loss. Radiologic: fracture healing and failure of fixation. Clinical: pain, social functioning score, and mobility score.\n The minimum follow-up was one year. We did not find any statistically significant difference, intraoperatively, radiologically, or clinically, between the two groups of patients.\n There is no advantage to an intramedullary nail versus a sliding compression hip screw for low-energy pertrochanteric fractures AO/OTA 31-A1 and A2, specifically with its increased cost and lack of evidence to show decreased complications or improved patient outcome.", "To compare the surgical complications and functional outcome of the Gamma nail intramedullary fixation device versus the Richards sliding hip screw and plate device in intertrochanteric femoral fractures.\n A prospective, randomised controlled clinical trial with observer blinding.\n A regional teaching hospital in the United Kingdom.\n All patients admitted from the local population with intertrochanteric fractured femurs were included. There were 400 patients entered into the study and 399 followed-up to one year or death.\n The devices were assigned by randomization to either a short-type Gamma nail (203 patients) or a Richard's-type sliding hip screw and plate (197 patients).\n The main surgical outcome measurements were fixation failure and reoperation. A functional outcome of pain, mobility status, and range of movement were assessed until one year.\n The requirement for revision in the Gamma nail group was twelve (6%); for Richard's group, eight (4%). This was not statistically different (p = 0.29; odds ratio, 1.48 [0.59-3.7]). A subcapital femoral fracture occurred in the Richard's group. Femoral shaft fractures occurred with four in the Gamma nail group (2%) and none in the Richard's group (p = 0.13). Three required revision to another implant. Lag-screw cut-out occurred in eight patients in the gamma nail group (4%) and four in the Richard's group (2%). This was not statistically significant (p = 0.37; odds ratio, 2.29 [0.6-9.0]). The development of other postoperative complications was the same in both groups. There was no difference between the two groups in terms of early or long-term functional status at one year.\n The use of an intramedullary device in the treatment of intertrochanteric femoral fractures is still associated with a higher but nonsignificant risk of postoperative complications. Routine use of the Gamma nail in this type of fracture cannot be recommended over the current standard treatment of dynamic hip screw and plate.", "The purpose of this study is to compare a cephalomedullary nail that uses a piriformis fossa starting point to one that uses a trochanteric starting point, in the treatment of high-energy proximal femur fractures in young patients. Our hypothesis was that a nail that uses a trochanteric starting point would result in less blood loss than a nail that uses a piriformis fossa starting point.\n Prospective, randomized.\n Level 1 trauma center.\n Thirty-four consecutive patients aged between 18 and 50 years who sustained a subtrochanteric, intertrochanteric, or ipsilateral femoral neck/shaft fracture due to a high-energy injury were enrolled.\n Patients were randomized to have their fractures repaired with a Russell-Taylor Recon Nail or Howmedica Long Gamma Nail. Surgery was performed on a fracture table, in supine or lateral position according to the surgeon's preference. Direct fracture exposure was avoided. Reduction was obtained through traction, patient positioning, and manual pressure. If necessary, stab-wound incisions were made to introduce instruments to improve reduction. Intramedullary reamers were used, and all nails were statically locked. Bone grafting was not used.\n Blood loss, incision length, duration of surgery, and body mass index were recorded for each patient. Surgeon's assessment of ease of use of the device and quality of reduction were noted. Patients were to be followed up to assess fracture union. Hip and knee ranges of motion at latest follow-up were measured. Radiographs obtained at the time of union were assessed for varus malalignment. Return to work status was recorded, and the Harris Hip Score was used to assess hip function.\n There were 17 patients in each group. The 2 groups did not differ with regard to blood loss, incision length, and duration of surgery or intraoperative complications. Body mass index was significantly linked to duration of surgery (P<0.001) and incision length (P<0.001). Surgeon's assessment of ease of use and reduction quality for the two devices did not differ. The rate of varus malunion did not differ between the 2 groups. Two patients were lost to follow-up before fracture union. All other fractures healed with no need for bone grafting or other procedures to obtain union. One obese patient developed a wound infection that resolved after debridement and a course of antibiotics. A total of 6 patients were lost prior to their 1-year follow-up visit. Among the remaining 28 patients, at an average follow-up of 14 months, no difference was noted between the 2 groups with regard to return to work status, Harris Hip Score, or hip and knee ranges of motion.\n Both devices yield predictably good results in these difficult fractures. We found no difference between the two devices with regard to incision length, duration of surgery, blood loss, reduction, ease of use, union rate, complication rate, or outcome.", "Intramedullary nailing has been the gold standard in the management of lower limb fractures by virtue of advantage of early joint mobilisation and weight bearing. They are being increasingly used in the peri-trochanteric fractures of femur. Biomechanical studies have proved the supremacy of single femoral neck screw construct over two femoral neck screws along with the intramedullary nails in osteoporotic bones due to lower incidence of complications. This randomised clinical trial was conducted to study the clinico-radiological outcome of single and two-femoral neck screw construct in the management of unstable trochanteric fractures in the elderly osteoporotic bones. Although there was no significant difference in the clinical outcome in the two groups, less sliding of the femoral neck screws was noted with two-femoral neck screw configuration. The tip-apex distance was also significantly lower in the two-screw construct compared to that of the single screw construct. This study to our knowledge is the first randomised control clinical trial evaluating the effectiveness of one and two femoral neck screw configuration of intra-medullary nails in the management of unstable trochanteric fractures.", "The current prospective and randomized study was done to determine whether fixation of intertrochanteric femoral fractures that lack a medial buttress with a dynamically locked intramedullary hip screw prevents proximal stress shielding. Stress shielding was evident by the presence of cortical hypertrophy at the level of the tip of the nail and often was associated with midthigh pain. Of the 80 patients enrolled in this trial, 64 still were alive after 1 year. Among these patients, 30 had the nail classically locked with two screws transfixing the nail in two separate holes (Group A), and 34 had the nail locked with one screw passing through a slot (Group B). The average duration of followup was 37 months (range, 12-49 months). Tolerance to dynamically locked nails was significantly better, with only one patient in Group B having cortical hypertrophy of the femur at the level of the tip of the nail, compared with six patients in Group A. Other outcomes were equal in both groups. Late tolerance to this new dynamically locked intramedullary hip screw is good, while retaining the known advantages of nailing of these fractures.", "This study aimed at comparing the results obtained with a sliding screw plate and an experimental device including a small-diameter nail that can be placed with a mini-invasive approach and provides a stable fixation.\n Randomized prospective study.\n University hospital.\n The study included two groups with thirty fractures of the trochanteric area.\n In both groups, the surgical procedure was carried out on patients placed on a traction table in a supine position, under an x-ray amplifier. Sliding screw plates (THS) were set in place according to the usual open technique. Nails were placed through a twenty-millimeter supratrochanteric cutaneous incision. This experimental system comprised a locked intramedullary nail with two nonparallel seven-millimeter cervicocephalic screws.\n The comparison between the two groups was based on the surgical procedure (time, duration of x-ray irradiation, and total blood loss); the initial postoperative period (complications, duration of hospital stay, and the time before returning home); the time before full weight bearing became effective; the functional and social recovery; mortality; and the quality of immediate and final anatomic restitution and healing.\n Operating time (p < 0.001) and blood loss (p < 0.001) were lower in the nail group, and no blood transfusion was required. Postoperative pain (p < 0.01), time necessary to support full weight bearing (p < 0.02), and time before returning home (p < 0.05) were reduced in the nail group. All fractures healed in the same amount of time, with good anatomic results in the nail group, whereas ten impactions beyond ten millimeters occurred in the plate group. No difference was found between the two groups in walking ability and autonomy recovery, but hip function (p < 0.05) was better in the nail group.\n This preliminary clinical study has shown the advantages of this mini-invasive technique. It could not evaluate all the possible disadvantages inherent in the method. These points will be evaluated in a multicenter study justified by these preliminary results." ]

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[ "The effect of a series of repetitive transcranial magnetic stimulations of the motor cortex on central pain after spinal cord injury.", "Transcranial magnetic stimulation for pain control. Double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy.", "Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia.", "Motor cortex rTMS in chronic neuropathic pain: pain relief is associated with thermal sensory perception improvement.", "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.", "A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury.", "Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I.", "A pilot study investigating the effects of fast left prefrontal rTMS on chronic neuropathic pain.", "Effect of repetitive transcranial magnetic stimulation over the hand motor cortical area on central pain after spinal cord injury.", "[Central and peripheral deafferent pain: therapy with repetitive transcranial magnetic stimulation].", "Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain.", "Reduction of intractable deafferentation pain due to spinal cord or peripheral lesion by high-frequency repetitive transcranial magnetic stimulation of the primary motor cortex.", "Repetitive transcranial magnetic stimulation for the treatment of chronic pain - a pilot study.", "Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial.", "Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain.", "Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex.", "Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS.", "A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia.", "Pain relief by rTMS: differential effect of current flow but no specific action on pain subtypes.", "Long-term effect of repetitive transcranial magnetic stimulation on motor function recovery after acute ischemic stroke.", "Low-frequency rTMS promotes use-dependent motor plasticity in chronic stroke: a randomized trial.", "Effects of anodal transcranial direct current stimulation on chronic neuropathic pain in patients with multiple sclerosis.", "Transcranial DC stimulation coupled with TENS for the treatment of chronic pain: a preliminary study.", "A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients.", "Efficacy of repetitive transcranial magnetic stimulation for the treatment of refractory chronic tinnitus: a randomized, placebo controlled study.", "Prefrontal repetitive transcranial magnetic stimulation as add on treatment in depression.", "Inhibition of the unaffected motor cortex by 1 Hz repetitive transcranical magnetic stimulation enhances motor performance and training effect of the paretic hand in patients with chronic stroke.", "Improvement of dexterity by single session low-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex in acute stroke: a double-blind placebo-controlled crossover trial.", "Repetitive transcranial magnetic stimulation for ALS. A preliminary controlled study." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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", "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 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.", "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.", "In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency < or = 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression.", "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.", "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.", "Although there is evidence for short term benefits of rTMS in stroke, longer term effects have not been reported. The aim of the study was to evaluate the effect of two different frequencies of rTMS on motor recovery and on cortical excitability up to 1 year post-treatment.\n Forty-eight patients with acute ischemic stroke were randomly classified into three groups. The first two groups received real rTMS over motor cortex (3 and 10 Hz respectively) of the affected hemisphere and the third group received sham stimulation of the same site, daily for five consecutive days. Disability was assessed before, after fifth sessions, and then after 1, 2, 3 and 12 months. Cortical excitability was assessed for both hemispheres before and after the second and fifth sessions.\n A significant 'rTMS x time' interaction was obtained indicating that real and sham rTMS had different effects on rating scales. This was because real rTMS produced greater improvement than sham that was evident even at one year follow-up. These improvements were associated with changes in cortical excitability over the period of treatment.\n These results confirm that real rTMS over motor cortex can enhance and maintain recovery and may be a useful add on therapy in treatment of acute stroke patients.", "To investigate the long-term behavioral and neurophysiologic effects of combined time-locked repetitive transcranial magnetic stimulation (rTMS) and physical therapy (PT) intervention in chronic stroke patients with mild motor disabilities.\n Thirty patients were enrolled in a double-blind, randomized, single-center clinical trial. Patients received 10 daily sessions of 1 Hz rTMS over the intact motor cortex. In different groups, stimulation was either real (rTMS(R)) or sham (rTMS(S)) and was administered either immediately before or after PT. Outcome measures included dexterity, force, interhemispheric inhibition, and corticospinal excitability and were assessed for 3 months after the end of treatment.\n Treatment induced cumulative rebalance of excitability in the 2 hemispheres and a reduction of interhemispheric inhibition in the rTMS(R) groups. Use-dependent improvements were detected in all groups. Improvements in trained abilities were small and transitory in rTMS(S) patients. Greater behavioral and neurophysiologic outcomes were found after rTMS(R), with the group receiving rTMS(R) before PT (rTMS(R)-PT) showing robust and stable improvements and the other group (PT-rTMS(R)) showing a slight improvement decline over time.\n Our findings indicate that priming PT with inhibitory rTMS is optimal to boost use-dependent plasticity and rebalance motor excitability and suggest that time-locked rTMS is a valid and promising approach for chronic stroke patients with mild motor impairment. Classification of evidence: This interventional study provides Class I evidence that time-locked rTMS before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months poststroke.", "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.", "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.", "It has been recently shown that a single session of repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can improve motor function in stroke patients; however, this improvement is short-lasting. We therefore conducted a randomized, sham-controlled, phase II trial to evaluate whether five sessions of low-frequency rTMS can increase the magnitude and duration of these effects and whether this approach is safe.\n Fifteen patients with chronic stroke were randomized to receive active or sham rTMS of the unaffected hemisphere. A blinded rater assessed motor function and corticospinal excitability at baseline, during and after 2 weeks of treatment. Safety was assessed using a neuropsychologic battery and electroencephalogram.\n Active rTMS resulted in a significant improvement of the motor function performance in the affected hand that lasted for 2 weeks. These effects were not observed in the sham rTMS group (affected and unaffected hand) and in the unaffected hand in the active rTMS group. Corticospinal excitability decreased in the stimulated, unaffected hemisphere and increased in the affected hemisphere. There was a significant correlation between motor function improvement and corticospinal excitability change in the affected hemisphere. Cognitive performance and electroencephalogram were not changed significantly throughout the trial in both groups of treatment.\n These results support and extend the findings of previous studies on rTMS in stroke patients because five consecutive sessions of rTMS increased the magnitude and duration of the motor effects. Furthermore, this increased dose of rTMS is not associated with cognitive adverse effects and/or epileptogenic activity.", "The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Low frequency rTMS applied over the auditory cortex has been proposed as a new and causally oriented treatment approach for pathological conditions with abnormal, increased cortical activity including tinnitus with increased activity in the auditory cortex. However available studies are characterized by a positive reports on the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for treatment of tinnitus, there are few details about the duration of specific treatment effects.\n The design of the study was randomized, prospective, placebo-controlled. Right-handed patients were treated with either real or sham 1 Hz frequency rTMS over a period of two weeks. Fifty-two patients with chronic, treatment resistant tinnitus and stable medication were enrolled in the study after giving written informed consent and forty-two patients completed the study and were included in data analysis.\n The ability to reduce the symptoms of tinnitus appeared in both randomized groups immediately after the 1 Hz rTMS and sham stimulation phase. There was a significant reduction in both groups of the tinnitus total score on the Tinnitus Handicap Inventory (THI) (real rTMS p=0.005; sham rTMS p=0.049) and Tinnitus Questionnaire (TQ) total score (real rTMS p=0.003; sham rTMS p=0.049). On the THI evaluation scale, in the real rTMS a mild worsening was noted during week 6 in comparison with the state attained in week 2. During the subsequent course of the study a significant reduction of the total score persisted in the case of THI (real rTMS week 14 p=0.033 and borderline week 26 p=0.058). The reduction of symptoms as evaluated using the TQ was significant compared to baseline in the real rTMS group at week 2, 6 and 14 (p=0.003; p=0.024; p=0.022). The group treated with sham stimulation reached significant reduction of symptoms only at week 2 (p=0.049). A comparison of the difference in the recorded values of the total score during follow-up in relation to baseline expressed as a percentage demonstrates the difference in the effect of rTMS and sham stimulation as evaluated by both the basic scales. Graphical analysis of mean patterns of treatment response according to stimulation type shows a similarity between treatment response patterns evaluated by reduction of the total scores using THI and TQ.\n The principal finding of this study is that real 1 Hz rTMS treatment was capable of significantly reducing the total baseline score of basic scales that measure tinnitus severity. This result is important as it proves that significant reduction of symptoms can be achieved even in a group of patients with long-term symptoms resistant to pharmacological treatment.", "A growing number of studies report antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The hypothesis that high frequency (20 Hz) rTMS (HF-rTMS) may speed up and strengthen the therapeutic response to sertraline in MD was tested. Twenty eight patients who had not yet received medication for the present depressive episode (n=12) or had failed a single trial of an antidepressant medication (n=16) were started on sertraline and randomised to receive either real of sham HF-rTMS. HF-rTMS was applied to the left dorsolateral prefrontal area in daily sessions (30 trains of 2 s, 20-40 s intertrain interval, at 90% motor threshold) on 10 consecutive working days. The results suggest that in this patient population, HF-rTMS does not add efficacy over the use of standard antidepressant medication.", "Recent reports demonstrated that low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere improved the affected hand function in chronic stroke patients. We investigated whether 1 Hz rTMS improved the motor learning of the affected hand in patients after stroke.\n A double-blind study.\n Twenty patients with chronic subcortical stroke.\n The patients were randomly assigned to receive either a sub-threshold rTMS over the unaffected hemisphere (1 Hz, 25 minutes) or sham stimulation, and all patients performed a pinching task after stimulation. We evaluated the motor function of the affected hand and the excitatory and inhibitory function of the affected motor cortex by transcranial magnetic stimulation.\n Compared with sham stimulation, rTMS induced an increase in the excitability of the affected motor cortex(p < 0.001) and an improvement in acceleration of the affected hand (p = 0.006). Moreover, the effect of motor training on pinch force was enhanced by rTMS (p < 0.001). These improvement in the motor function lasted for one week after rTMS and motor training (p < 0.001).Conclusion: rTMS improved the motor learning of the affected hand in patients after stroke; thus, it can apply as anew rehabilitation strategy for patients after stroke.", "Increasing evidence suggests that the contralesional motor cortex (M1) inhibits the ipsilesional M1 in stroke patients. This inhibition could impair motor function of the affected hand. We investigated if inhibitory 1~Hz repetitive transcranial magnetic stimulation (rTMS) over the contralesional M1 improved motor performance of the affected hand in acute stroke.\n A double-blind study of real versus placebo rTMS was conducted. Twelve patients early after subcortical stroke (mean: 7 days) received 1200 stimuli of real and placebo rTMS in a crossover design. The sequence of stimulations was counterbalanced across subjects. Stimulus intensity was subthreshold (90% of motor threshold at rest). Motor function was tested by grip strength recordings and Nine Hole Peg Test (NHPT) executions before and after each rTMS session.\n Compared to sham stimulation, real rTMS improved NHPT results but not grip strength in the affected hand. No change of performance was observed for the unaffected hand. NHPT baseline repetitions in a subgroup of patients indicated stable motor performance prior to the rTMS sessions.\n The study suggests that therapeutic rTMS applications over the contralesional hemisphere are feasible in acute stroke patients and can transiently improve dexterity of the affected hand. RTMS may become an additional tool for early neurorehabilitation.", "Repetitive transcranial magnetic stimulation (rTMS) of brain can modulate cortical neurotransmission, a novel paradigm of repetitive stimulation termed continuous theta-burst stimulation (cTBS) produces a pronounced and prolonged suppression of motor cortex excitability. The aim of this preliminary study was to investigate whether cTBS of motor cortex could have any beneficial effect in patients with amyotrophic lateral sclerosis (ALS). We performed a double-blind, placebo-controlled trial. Twenty patients with definite ALS were randomly allocated to blinded active or placebo stimulation. Repetitive stimulation of the motor cortex was performed for five consecutive days every month for six consecutive months. The primary outcome was the rate of decline as evaluated with the ALS functional rating scale. The treatment was well tolerated by the patients. Fifteen patients (seven active and eight sham) completed the study and were included in the 6-months analysis. Both active and sham patients deteriorated during treatment, however, active patients showed a modest but significant slowing of the deterioration rate. Though we cannot be sure whether the effects observed can be attributed to cTBS, because of the restricted number of patients studied, further investigation on a larger group of ALS patients is warranted. The results of the pilot study might open up a new therapeutic perspective in ALS based on neuromodulation." ]

[ "20200346" ]

[ "Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe." ]

[ "There is some evidence that statins may have a protective and symptomatic benefit in Alzheimer disease (AD). The LEADe study is a randomized controlled trial (RCT) evaluating the efficacy and safety of atorvastatin in patients with mild to moderate AD.\n This was an international, multicenter, double-blind, randomized, parallel-group study. Subjects had mild to moderate probable AD (Mini-Mental State Examination score 13-25), were aged 50-90 years, and were taking donepezil 10 mg daily for > or 3 months prior to screening. Entry low-density lipoprotein cholesterol levels (LDL-C) were > 95 and < 195 mg/dL. Patients were randomized to atorvastatin 80 mg/day or placebo for 72 weeks followed by a double-blind, 8-week atorvastatin withdrawal phase. Coprimary endpoints were changes in cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog]) and global function (Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS-CGIC]) at 72 weeks.\n A total of 640 patients were randomized in the study. There were no significant differences in the coprimary endpoints of ADAS-cog or ADCS-CGIC or the secondary endpoints. Atorvastatin was generally well-tolerated.\n In this large-scale randomized controlled trial evaluating statin therapy as a treatment for mild to moderate Alzheimer disease, atorvastatin was not associated with significant clinical benefit over 72 weeks. This treatment was generally well-tolerated without unexpected adverse events. Classification of evidence: This study provides Class II evidence that intensive lipid lowering with atorvastatin 80 mg/day in patients with mild to moderate probable Alzheimer disease (aged 50-90), taking donepezil, with low-density lipoprotein cholesterol levels between 95 and 195 mg/dL over 72 weeks does not benefit cognition (as measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale) (p = 0.26) or global function (as measured by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change) (p = 0.73) compared with placebo." ]

[ "12600912", "20104528", "12124559", "11072938", "18285698", "9684133", "12900820", "15599680", "9197872" ]

[ "The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: a randomized, controlled trial.", "Incidence of cancers, ischemic cardiovascular diseases and mortality during 5-year follow-up after stopping antioxidant vitamins and minerals supplements: a postintervention follow-up in the SU.VI.MAX Study.", "Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation?", "Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial.", "Effects of low- and high-flux dialyzers on oxidative stress and insulin resistance.", "Antioxidant treatment during liver resection for alleviation of ischemia-reperfusion injury.", "Effects of exercise training on coronary heart disease risk factors in renal transplant recipients.", "[Investigation of antioxidant therapy with sodium selenite in acute pancreatitis. A prospective randomized blind trial].", "Antioxidants in the treatment of severe pre-eclampsia: an explanatory randomised controlled trial." ]

[ "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.", "The Supplementation in Vitamins and Mineral Antioxidants Study was a double-blind, placebo-controlled, randomized trial, in which 12,741 French adults (7,713 women aged 35-60 years and 5,028 men aged 45-60 years) received a combination of ascorbic acid (120 mg), vitamin E (30 mg), beta-carotene (6 mg), selenium (100 microg) and zinc (20 mg), or placebo daily for a median follow-up time of 7.5 years [October 1994 to September 2002]. Antioxidant supplementation decreased total cancer incidence and total mortality in men. Postintervention follow-up assessment of total cancer incidence, ischemic cardiovascular disease incidence and total mortality was carried out for 5 years [September 1, 2002, to September 1, 2007]. No late effect of antioxidant supplementation was revealed 5 years after ending the intervention neither on ischemic cardiovascular disease incidence and mortality in both genders nor on cancer incidence in women. Regarding duration of intervention effects in men, the reduced risk of total cancer incidence and total mortality was no longer evident after the 5-year postintervention follow-up. During the postsupplementation period, the relative risk (RR) for total cancer incidence (n = 126) was 0.98 (95% confidence interval [CI], 0.75-1.27) among antioxidant recipients compared to nonrecipients. For total mortality (n = 90), the RR was 0.98 (95% CI, 0.75-1.26) for men receiving antioxidants compared to nonrecipients. In conclusion, beneficial effects of antioxidant supplementation in men disappeared during postintervention follow-up.", "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.", "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.", "Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease (ESRD). The cornerstone of high CVD incidence in ESRD patients is endothelial dysfunction which results from inflammation, oxidative stress and insulin resistance. Although various modalities of hemodialysis (HD) have been presumed to exert different effects on oxidative stress and insulin resistance, solid evidence is still lacking.\n 40 ESRD patients undergoing HD were prospectively enrolled and divided randomly into two groups. Patients in each group received either F8 HPS (low-flux) (Group A) or FX80 (high-flux) (Group B) as HD dialyzers for 2 consecutive months. Diet pattern and medications were kept as usual in both groups to avoid considerable blood glucose change during study period. Blood samples were taken at the start and end of the study.\n A total of 38 patients (18 and 20 for Groups A and B, respectively) completed the study. Within each group, there was no change in adiponectin, plasma 8-iso-prostaglandin F(2)(alpha), high-sensitivity C-reactive protein, blood glucose and insulin after 2 months of treatment except a significant change of HOMA(IR) (p = 0.02) in high-flux group. The significant change of HOMA(IR) between the two groups (p = 0.017) mainly results from the parallel change of insulin between the two groups (p = 0.03).\n For patients receiving HD, the high-flux dialyzer with synthetic polysulfone membranes fails to provide a better anti-inflammatory or antioxidative effect than the low-flux dialyzer; however, the high-flux dialyzer does significantly improve insulin resistance in this short-term study. This result implies that the high-flux dialyzer might provide better cardiovascular protection than the low-flux dialyzer. Therefore, the low-flux dialyzer might be considered for patients who only need short-term HD therapy. Regarding patients under long-term maintenance HD therapy, a high-flux dialyzer might be the choice of dialyzer.\n Copyright 2008 S. Karger AG, Basel.", "Many experimental studies on ischemia-reperfusion injury in animals suggest a preventive effect of antioxidants, but the clinical significance of these findings is still unclear. The aim of our study was to evaluate the effect of antioxidant treatment with vitamins on liver function parameters during liver resection.\n Our prospective randomized study comprised 58 patients undergoing major liver surgery, including the Pringle maneuver. In the treatment group 32 patients received a multivitamin infusion (Omnibionta) which included 10 mg of alpha-tocopherol acetate, 2 mg of DL-alpha-tocopherol and 1 g of ascorbate. The control group consisted of 26 patients. Various parameters associated with liver function, such as transaminases, lactate, ammonia, bilirubin, cholinesterase and clotting parameters were measured preoperatively, at the beginning of liver ischemia, 15, 30 and 60 minutes after reperfusion onset and every 12 hours after the operation.\n The Mann-Whitney-Wilcoxon-Test showed statistically significant differences in the postischemic changes between the treatment group and the control group for the Quick test (prothrombin time): p = 0.01. The transaminases were also markedly better in the treatment group (splitting-up slightly more delayed than with the Quick test). A smaller effect was seen with cholinesterase. Lactate, however, increased intraoperatively with a strong correlation to the duration of ischemia and returned quickly to baseline values without any remarkable influence of the antioxidant treatment.\n In our study, antioxidant treatment with a multivitamin infusion showed a positive effect on postischemic liver function parameters.", "Multiple risk-factor interventions that include lifestyle changes have been proved to be effective in reducing risk profile in persons at high risk for developing coronary heart disease (CHD). There have not been similar studies involving transplant recipients. The purpose of this study is to examine effects of exercise training on cardiovascular risk profile during the first year after renal transplantation. We used traditional CHD risk factors and the Framingham CHD prediction methods.\n Ninety-six transplant recipients were randomly assigned to 2 groups at 1 month posttransplantation: the exercise training (EX group; n = 51) and usual care groups (UC group; n = 45). Testing was performed at baseline and 12 months posttransplantation and included maximal exercise testing and evaluation of CHD risk factors and risk-factor categories, determined by means of the Framingham equations.\n Overall 10-year CHD risk score did not change in either group. All patients showed increases in total cholesterol (TC) level, high-density lipoprotein fraction of cholesterol (HDL-C), and body mass index over time. No differences were observed between groups, except for a trend toward greater improvement in HDL cholesterol levels in the EX group (P = 0.07). Significantly more patients in the EX group moved out of the high-risk category in TC-HDL ratio. All patients remained in the high-risk category for physical fitness. There was a significant negative correlation of CHD risk and maximal exercise capacity (r = -0.406; P < 0.001).\n Exercise training alone does not reduce CHD risk during the first year after transplantation. Research to determine the effects of multiple risk interventions during a longer period in transplant recipients is warranted.", "Oxygen free radicals appear in the early phase of acute pancreatitis followed by an imbalance between the oxygen and anti-oxygen system. Sodium selenite may play an important role in the reduction of radicals in experimental pancreatitis. The aim of this study was to evaluate the effects of selenium in a clinical prospective trial.\n 70 patients with acute pancreatitis were prospectively allocated to a selenium and a placebo group. Clinical and paraclinical parameters were investigated with a follow-up of 90 days after hospital stay.\n The clinical course of the two treatment groups did not show statistically significant differences. Five patients in the selenium and three patients in the placebo group died. Depending on selenium therapy, antioxidant substances were presented in higher levels. All 17 clinical parameters showed no statistical significance.\n Substitution of sodium selenite has no beneficial effect on the clinical outcome of patients with acute pancreatitis.", "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." ]

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

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

[ "18575629", "18568115" ]

[ "A vaccine against nicotine for smoking cessation: a randomized controlled trial.", "Extended use of nicotine replacement therapy to maintain smoking cessation in persons with schizophrenia." ]

[ "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.", "This study was designed to determine the feasibility and efficacy of long-term nicotine replacement therapy (NRT) in helping persons with schizophrenia remain tobacco-free. Fifty smokers with a diagnosis of schizophrenia or schizo-affective disorder and whose symptoms had been stable for at least two months were enrolled in a program providing group support and NRT (patches) in individually adjusted doses set to maintain baseline nicotine intake. All participants attended weekly group support/motivation sessions. Smoking activity was determined by measuring carbon monoxide levels in expired air. Participants who quit tobacco use completely during the first three months were entered into a single-blind phase in which they received either placebo or active nicotine patches for up to six additional months, along with biweekly group sessions. Sixty days into the open-label phase, 66% of the subjects had reduced their use of tobacco by at least 75%. After 90 days of open-label treatment, 18 subjects (36%) were tobacco-free and qualified to enter the six-month, single-blind phase, eight on placebo and nine on active patches. A significantly greater proportion of those on placebo (8 of 8) compared with those on active patches (3 of 9) relapsed prior to completion of the 6-month period. This difference is statistically significant at the p = 0.009 level. The results of this study indicate that long-term use of NRT is feasible and effective for sustained tobacco-free success and may be an important strategy for reducing health risks due to tobacco use in this special population." ]

[ "10212082", "9722255", "11158452", "9024451", "11530870", "12534029" ]

[ "Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome.", "Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity.", "A multicenter, randomized open study of early corticosteroid treatment (OSECT) in preterm infants with respiratory illness: comparison of early and late treatment and of dexamethasone and inhaled budesonide.", "Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis.", "The effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes.", "[Value of prenatal corticotherapy in the prevention of hyaline membrane disease in premature infants. Randomized prospective study]." ]

[ "To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.\n Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications.\n More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects.\n These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.", "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.", "To compare early (<3 days) with late (>15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease.\n Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age <30 weeks, postnatal age <72 hours, and need for mechanical ventilation and inspired oxygen concentration >30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (<72 hours) dexamethasone, early budesonide, delayed selective (>15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily.\n There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance.\n Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective.", "To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).\n Prospective, controlled, randomized study.\n Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.\n No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.\n Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly.", "This study was carried out to examine the effect of antenatal corticosteroid therapy on pregnancies complicated by premature rupture of membranes (PROMs). For this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation) complicated by PROMs were evaluated prospectively during the period January 1997 to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince Zaid). Patients were allocated into two groups; Group 1 included 72 patients treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group 2 which included 67 patients whoreceived no treatment (control group). All women were examined clinically and the diagnosis of PROMs was demonstrated using vaginal speculum, nitrazine paper examination and ultrasonography. All neonates were evaluated clinically, radiologically, and by laboratory investigations. Pearson's Chi-square and Fisher's exact tests were used to assess the significance of differences between the two study groups. Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), and days of hospital stay were significantly reduced in premature infants of the corticosteroid treated women compared with the controls (p<0.04, p<0.04, p<0.04, and p<0.05, respectively). The perinatal mortality was significantly decreased among the corticosteroid treated group in the gestational subgroups 31-32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was statistically a significant factor which resulted in increased perinatal mortality in the control group (p=0.02). Regarding the occurrence of postpartum endometritis there was a statistically significant increase among the corticosteroid treated group compared with the controls (p<0.04). Conclusion: Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a positive influencing effect on premature infants between 31 and 34 weeks of gestation, decreasing significantly the perinatal morbidity and mortality. It should be used with particular relevance to the developing world where surfactant is not available or where neonatal intensive care units are lacking.", "The aim of the study was to determine the feasibility, the cost and the effects of antenatal maternal corticosteroid treatment on preventing respiratory distress syndrome in premature neonates of our population.\n Between January, 1, 1998 and June, 31, 1999, 118 pregnant women at 26-34 weeks' gestation and at a high risk of premature delivery, were prospectively randomized in 2 groups: group 1 received intramusculary 24 mg of betamethasone (12 mg every 24 hours), group 2 didn't receive antenatal corticosteroids. At birth, premature neonates were systematically examined by a neonatologist.\n 131 premature neonates were born (63 from group 1, 68 from group 2). The incidence and the degree of severity of respiratory distress syndrome, appeared substancially reduced (4.8% vs 27.9%) by the use of antenatal corticosteroids. Moreover, neonatal mortality due to respiratory distress syndrome was statistically less in group 1 than in group 2 (22.9% vs 57%). There was no significant difference in the occurrence of maternal or neonatal corticosteroid complications such as infection between treated group and control subjects. We estimated a potential annual savings of 21 thousands tunisian dinars, when the cost implications for antenatal corticosteroid therapy were estimated to 2 thousands tunisian dinars.\n Maternal administration of corticosteroids before preterm delivery results in a decrease in the incidence and severity of respiratory distress syndrome and a decrease in neonatal mortality rate among premature neonates born to treated versus untreated mothers at 26-34 weeks' gestation; added to an annual savings estimated to 21 thousands tunisian dinars." ]

[ "18490891", "17661342", "16135471", "16462503", "20651011", "21689848", "15022300", "16618589", "10326708", "16488348", "15774341", "17848814", "15484202", "11689579", "20706112", "12096292", "14710804", "16643264", "15274068", "20467301", "20531162", "11879296", "17513815", "15338385", "11742045" ]

[ "A brief intervention for fatigue management in breast cancer survivors.", "A randomized controlled trial to evaluate the effectiveness of a brief, behaviorally oriented intervention for cancer-related fatigue.", "Randomized controlled trial of an educational intervention for managing fatigue in women receiving adjuvant chemotherapy for early-stage breast cancer.", "Will improvement in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer?", "Cancer-related fatigue and rehabilitation: a randomized controlled multicenter trial comparing physical training combined with cognitive-behavioral therapy with physical training only and with no intervention.", "A randomised controlled trial testing the feasibility and efficacy of a physical activity behavioural change intervention in managing fatigue with gynaecological cancer survivors.", "A randomized clinical trial of energy conservation for patients with cancer-related fatigue.", "Nursing education as an intervention to decrease fatigue perception in oncology patients.", "Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy.", "Supportive intervention for fatigue in patients undergoing chemotherapy: a randomized controlled trial.", "A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment.", "Randomized controlled trial of a structured training program in breast cancer patients with tumor-related chronic fatigue.", "Exercise manages fatigue during breast cancer treatment: a randomized controlled trial.", "Randomized trial of coordinated psychosocial interventions based on patient self-assessments versus standard care to improve the psychosocial functioning of patients with cancer.", "A pilot study to examine the feasibility and effects of a home-based aerobic program on reducing fatigue in children with acute lymphoblastic leukemia.", "Pain and fatigue management: results of a nursing randomized clinical trial.", "Feasibility of exercise during treatment for multiple myeloma.", "Does routine assessment and real-time feedback improve cancer patients' psychosocial well-being?", "A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma.", "A randomized controlled trial of home-based exercise for cancer-related fatigue in women during and after chemotherapy with or without radiation therapy.", "Therapeutic exercise during outpatient radiation therapy for advanced cancer: Feasibility and impact on physical well-being.", "Fatigue and quality of life outcomes of exercise during cancer treatment.", "Impact of a peer-delivered telephone intervention for women experiencing a breast cancer recurrence.", "Effect of aerobic exercise and relaxation training on fatigue and physical performance of cancer patients after surgery. A randomised controlled trial.", "The effect of group psychosocial support on survival in metastatic breast cancer." ]

[ "The purpose of this randomized control trial was to verify the effectiveness of a brief group intervention that combines stress management psycho-education and physical activity (ie, independent variable) intervention in reducing fatigue and improving energy level, quality of life (mental and physical), fitness (VO 2submax), and emotional distress (ie, dependent variables) in breast cancer survivors. This study applied Lazarus and Folkman stress-coping theoretical framework, as well as Salmon's unifying theory of physical activity. Eighty-seven French-speaking women who had completed their treatments for nonmetastatic breast cancer at a university hospital in Quebec City, Canada, were randomly assigned to either the group intervention (experimental) or the usual-care (control) condition. Data were collected at baseline, postintervention, and at 3-month follow-up. The 4-week group intervention was cofacilitated by 2 nurses. Results showed that participants in the intervention group showed greater improvement in fatigue, energy level, and emotional distress at 3-month follow-up, and physical quality of life at postintervention, compared with the participants in the control group. These results suggest that a brief psycho-educational group intervention focusing on active coping strategies and physical activity is beneficial to cancer survivors after breast cancer treatments.", "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 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.", "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.", "Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial.\n This randomized controlled trial compared the effect on cancer-related fatigue of physical training combined with cognitive behavioral therapy with physical training alone and with no intervention.\n In this multicenter randomized controlled trial, 147 survivors of cancer were randomly assigned to a group that received physical training combined with cognitive-behavioral therapy (PT+CBT group, n=76) or to a group that received physical training alone (PT group, n=71). In addition, a nonintervention control group (WLC group) consisting of 62 survivors of cancer who were on the waiting lists of rehabilitation centers elsewhere was included.\n The study was conducted at 4 rehabilitation centers in the Netherlands.\n All patients were survivors of cancer.\n Physical training consisting of 2 hours of individual training and group sports took place twice weekly, and cognitive-behavioral therapy took place once weekly for 2 hours.\n Fatigue was assessed with the Multidimensional Fatigue Inventory before and immediately after intervention (12 weeks after enrollment). The WLC group completed questionnaires at the same time points.\n Baseline fatigue did not differ significantly among the 3 groups. Over time, levels of fatigue significantly decreased in all domains in all groups, except in mental fatigue in the WLC group. Analyses of variance of postintervention fatigue showed statistically significant group effects on general fatigue, on physical and mental fatigue, and on reduced activation but not on reduced motivation. Compared with the WLC group, the PT group reported significantly greater decline in 4 domains of fatigue, whereas the PT+CBT group reported significantly greater decline in physical fatigue only. No significant differences in decline in fatigue were found between the PT+CBT and PT groups.\n Physical training combined with cognitive-behavioral therapy and physical training alone had significant and beneficial effects on fatigue compared with no intervention. Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training.", "To determine the feasibility and efficacy of a physical activity behavioural change intervention in managing cancer-related fatigue among gynaecological cancer survivors during and post anti-cancer treatments.\n A two arm, single blind, randomised controlled trial was conducted within the Northern Ireland regional Cancer Centre. Thirty three sedentary gynaecological cancer survivors (stage I-III; ≤3 years post diagnosis), experiencing cancer-related fatigue (mild-severe) took part. Participants were randomly assigned to a behavioural change, moderate intensity physical activity intervention (n=16) or a Contact Control group (n=17). The primary outcome was fatigue (Multidimensional Fatigue Symptom Inventory-Short Form and Functional Assessment in Chronic Illness Therapy-Fatigue subscale). Secondary outcomes included quality of life, physical functioning, positive and negative affect, depression, body composition, sleep dysfunction and self-reported physical activity. Feasibility was assessed based on the recruitment rate, programme and physical activity adherence and participants' programme evaluation, including optional focus groups (n=16).\n Twenty five percent of eligible women took part (33/134). Participants were 8.7 (SD=9.1) months post diagnosis, with a mean age of 53 (SD=10.3) years. The majority of the sample had a diagnosis of ovarian (n=12) or endometrial cancer (n=11). Significant differences favouring the intervention group were observed for fatigue at 12 weeks and 6 months follow-up (12 week: mean difference=-11.06; 95% confidence interval (CI)=-21.89 to -0.23; effect size (d)=0.13; p=0.046; 6 month: mean difference=-19.48; 95% CI=-19.67 to -19.15; effect size (d)=0.20; p=0.01). A mean of 10 calls (SD=1.2 calls) were delivered to the Physical Activity Group, and 10 (SD=1.6 calls) to the CC group. The intervention was positively perceived based on exit questionnaire and focus group findings.\n A physical activity behavioural change intervention for gynaecological cancer survivors is feasible in terms of participants' programme adherence and evaluation, and the intervention demonstrates improvements in fatigue. However, confirmation in the form of a larger fully powered RCT is warranted.\n Copyright © 2011 Elsevier Inc. All rights reserved.", "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.", "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.", "Fatigue is a common and often severe problem in cancer patients undergoing chemotherapy. The authors postulated that physical activity training can reduce the intensity of fatigue in this group of patients.\n A group of cancer patients receiving high dose chemotherapy followed by autologous peripheral blood stem cell transplantation (training group; n = 27) followed an exercise program during hospitalization. The program was comprised of biking on an ergometer in the supine position following an interval training pattern for 30 minutes daily. Patients in the control group (n = 32) did not train. Psychologic distress was assessed at hospital admission and discharge with the Profile of Mood States and Symptom Check List 90.\n By the time of hospital discharge, fatigue and somatic complaints had increased significantly in the control group (P for both < 0.01) but not in the training group. Furthermore, by the time of hospital discharge, the training group had a significant improvement in several scores of psychologic distress (obsessive-compulsive traits, fear, interpersonal sensitivity, and phobic anxiety) (P value for all scores < 0.05); this outcome was not observed in the control group.\n The current study found that aerobic exercise can reduce fatigue and improve psychologic distress in cancer patients undergoing chemotherapy.", "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 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.", "Cancer-related fatigue is the most disabling symptom experienced by breast cancer patients following the cancer treatment. The positive effects of physical activity in the rehabilitation of breast cancer patients are documented in several studies. In a randomized controlled study the effects of a structured physical training program on fatigue and health-related quality of life were evaluated.\n 63 breast cancer patients with cancer-related chronic fatigue were randomized at the beginning of the inpatient rehabilitation. The control group received the standard complex rehabilitation program, the intervention group a structured physical training program and additional muscle strength and aerobic exercises. The effects of the treatment were evaluated by questionnaires at the start of rehabilitation (t1), end of rehabilitation (t2), and 3 months after t2 (t3). Isometric muscle strength and aerobic capacity were evaluated at t1 and t2.\n There was an improvement of muscle strength at the end of rehabilitation for both groups. The increase from t1 to t2 was significantly higher for the training group. The scores for global quality of life, physical well-being, and functionality increased from t1 to t2, but further improvement in the follow-up (t3) was only observed in the training group. The cancer-related fatigue was significantly reduced in the training group from t1 to t3, however, not in the control group.\n Structured physical training programs initiated during inpatient rehabilitation and continuously practiced in the time thereafter can improve symptoms of chronic fatigue and quality of life in breast cancer patients.", "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.", "To determine whether making patient-reported cancer needs, quality-of-life (QOL), and psychosocial information available to the health care team, allowing coordinated specifically targeted psychosocial interventions, resulted in reduced cancer needs, improved QOL, and increased satisfaction with care received.\n Self-reported cancer needs, QOL, and psychosocial information was collected from 450 people with cancer, using standardized questionnaires via a touch-screen computer. For a randomly chosen two thirds, this information was made available to the health care team who coordinated targeted psychosocial interventions. Information from the remaining one third was not seen. Patients were assessed 2 and 6 months after randomization for changes in their cancer needs, QOL, and psychosocial functioning and satisfaction with overall care received.\n There were no significant differences between the two arms with respect to changes in cancer needs, QOL, or psychosocial functioning between the baseline and follow-up assessments, nor with respect to satisfaction with care. However, for the subgroup of patients who were moderately or severely depressed at baseline, there was a significant reduction in depression for the intervention arm relative to the control arm at the 6-month assessment (P =.001).\n Making patient-reported cancer needs, QOL, and psychosocial data available to the health care team at a single consultation together with coordinated psychosocial interventions does not seem to reduce cancer needs nor improve QOL, psychosocial functioning, or satisfaction with the care received. However, identification of patients with moderate or severe levels of depression may be valuable in reducing subsequent levels of depression.", "Fatigue is one of the most frequent symptoms experienced by children with cancer during treatment. Effective management of fatigue is essential for improving children's quality of life.\n The aim of this study was to examine the feasibility of a home-based aerobic exercise intervention to reduce fatigue in children with acute lymphoblastic leukemia (ALL).\n A 6-week home-based aerobic exercise intervention was implemented for children who were in the intervention group, whereas patients in the control group received routine care. Multivariate analysis was used to examine the effects of the aerobic exercise intervention on the children's self-reported levels of fatigue at posttest and 1-month follow-up. Two types of analysis were used: intent-to-treat analysis and per-protocol analysis.\n This study was conducted with 22 children with ALL: 12 in the intervention group and 10 in the control group who were matched by age and sex. For per-protocol analysis, the finding indicated that children who received the exercise intervention reported significantly lower \"general fatigue\" subscale than those in the control group at the 1-month follow-up measurement. For intent-to-treat analysis, the findings indicated that there were no intervention and time effect for any of the 3 fatigue subscales at either posttest or 1-month follow-up.\n The finding indicated that the exercise program is feasible and warrants being tested in a clinical trial with a much larger sample of children for ALL.\n It suggests that a home-based exercise program may reduce fatigue for ALL children who are undergoing maintenance chemotherapy.", "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.", "Fatigue and insomnia are problems for patients with cancer. Research findings show that aerobic exercise decreases cancer-related fatigue. Because patients with cancer who have skeletal muscle wasting may not obtain maximum benefit from aerobic exercise training, exercise programs may need to include resistance training. Thus far, testing exercise as an intervention for fatigue has focused on patients with breast cancer and excluded patients with bone metastasis. There is a need to test the feasibility and effectiveness of exercise for patients with other types of cancer and with bone involvement. The effect of aerobic and strength resistance training on the sleep of patients with cancer has not been tested. A pilot/feasibility study with a randomized controlled design was conducted to investigate home-based exercise therapy for 24 patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation as treatment for multiple myeloma. None of the patients injured themselves. Because of the small sample size in the feasibility study, the effect of exercise on lean body weight was the only end point that obtained statistical significance. However, the results suggest that an individualized exercise program for patients receiving aggressive treatment for multiple myeloma is feasible and may be effective for decreasing fatigue and mood disturbance, and for improving sleep.", "This study examined the effectiveness of giving medical oncologists immediate feedback about cancer patients' self-reported psychosocial well-being in reducing those patients' levels of anxiety, depression, perceived needs and physical symptoms. Cancer patients attending one cancer centre for their first visit were allocated to intervention (n = 42) or control (n = 38) groups. All patients completed a computerized survey assessing their psychosocial well-being while waiting to see the oncologist. Intervention patients' responses were immediately scored and summary reports were placed in each patient's file for follow-up. A total of 48 participants (25 intervention and 23 control) completed the survey four times. Intervention patients who reported a debilitating physical symptom at visit 2 were significantly less likely to report a debilitating physical symptom at visit 3 compared with control patients (OR = 2.8, P = 0.04). Reductions in levels of anxiety, depression and perceived needs among intervention patients were not significantly different to control patients. Repeated collection and immediate feedback of patient-reported health information to oncologists has potential to improve patients' symptom control, but has little impact upon emotional well-being, including those at high risk. Future research should consider providing the feedback to other health professionals and patients, and monitor the impact on the process of individual patient care.", "Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental. Aerobic walking improves physical functioning and has been an intervention for chemotherapy-related fatigue. A prospective, randomized, controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma.\n Sixty-six men were randomized before they received radical radiotherapy for localized prostate carcinoma, with 33 men randomized to an exercise group and 33 men randomized to a control group. Outcome measures were fatigue and distance walked in a modified shuttle test before and after radiotherapy.\n There were no significant between group differences noted with regard to fatigue scores at baseline (P = 0.55) or after 4 weeks of radiotherapy (P = 0.18). Men in the control group had significant increases in fatigue scores from baseline to the end of radiotherapy (P = 0.013), with no significant increases observed in the exercise group (P = 0.203). A nonsignificant reduction (2.4%) in shuttle test distance at the end of radiotherapy was observed in the control group; however, in the exercise group, there was a significant increase (13.2%) in distance walked (P = 0.0003).\n Men who followed advice to rest and take things easy if they became fatigued demonstrated a slight deterioration in physical functioning and a significant increase in fatigue at the end of radiotherapy. Home-based, moderate-intensity walking produced a significant improvement in physical functioning with no significant increase in fatigue. Improved physical functioning may be necessary to combat radiation fatigue.", "Few studies have evaluated an individualized home-based exercise prescription during and after cancer treatment.\n The purpose of this study was to evaluate the effectiveness of a home-based exercise training intervention, the Pro-self Fatigue Control Program on the management of cancer-related fatigue.\n Participants (N = 119) were randomized into 1 of 3 groups: group 1 received the exercise prescription throughout the study; group 2 received their exercise prescription after completing cancer treatment; and group 3 received usual care. Patients completed the Piper Fatigue Scale, General Sleep Disturbance Scale, Center for Epidemiological Studies-Depression Scale, and Worst Pain Intensity Scale.\n All groups reported mild fatigue levels, sleep disturbance, and mild pain, but not depression. Using multilevel regression analysis, significant linear and quadratic trends were found for change in fatigue and pain (ie, scores increased, then decreased over time). No group differences were found in the changing scores over time. A significant quadratic effect for the trajectory of sleep disturbance was found, but no group differences were detected over time. No significant time or group effects were found for depression.\n Our home-based exercise intervention had no effect on fatigue or related symptoms associated with cancer treatment. The optimal timing of exercise remains to be determined.\n Clinicians need to be aware that some physical activity is better than none, and there is no harm in exercise as tolerated during cancer treatment. Further analysis is needed to examine the adherence to exercise. More frequent assessments of fatigue, sleep disturbance, depression, and pain may capture the effect of exercise.", "To characterize the feasibility of delivering a structured physical therapy (PT) program as part of a multidisciplinary intervention to patients undergoing outpatient radiation therapy for advanced cancer.\n A single-blinded, randomized, controlled trial at a quaternary medical center outpatient clinic. One hundred three adults undergoing radiation therapy for advanced cancer with prognoses > or =6 mos and 5-yr survival estimates < or =50% were randomized to usual care or participation in eight 90-min, multidisciplinary interventional sessions with 30 mins of each session devoted to PT. PT consisted of truncal and limb isodynamic strengthening targeting major upper- and lower-limb muscle groups as well as education and provision with instructional materials. Physical well-being and fatigue were assessed with Linear Analog Scale of Assessment. The Profile of Mood States-Short form, including Fatigue-Inertia and Vigor-Activity subscales, was also administered.\n PT session attendance was 89.3%. Relative to baseline, mean physical well-being Linear Analog Self Assessment scores at week 4 improved in the intervention group, 0.4 (SD, 23.6), and declined significantly in the control group, -10.0 (SD, 21.5) (P = 0.02). Fatigue and vigor were not significantly different between the groups. All intergroup differences had resolved at 8 and 27 wks. Baseline characteristics were not associated with the magnitude or direction of change in outcomes related to physical functioning.\n Delivery of a standardized resistive exercise PT intervention is feasible during outpatient radiation therapy and is associated with preserved physical well-being. However, benefits were not sustained, and fatigue was not affected.", "Despite the recognition of fatigue as a common and distressing symptom during cancer treatment, there are few evidence-based interventions available to manage such fatigue. The purpose of this multi-institutional pilot study was to explore the effects of a home-based moderate walking exercise intervention on fatigue, physical functioning, emotional distress, and quality of life (QOL) during breast cancer treatment.\n Fifty-two women were recruited from five university hospital outpatient departments for this pilot study with an experimental design. Subjects were randomly assigned to the walking program or to usual care during adjuvant chemotherapy or radiation therapy for breast cancer. Symptoms, physical functioning, and QOL were measured at baseline, midtreatment, and at the end of treatment.\n Women who exercised at least 90 minutes per week on 3 or more days reported significantly less fatigue and emotional distress as well as higher functional ability and QOL than women who were less active during treatment.\n A home-based walking exercise program is a potentially effective, low-cost, and safe intervention to manage fatigue and to improve QOL during adjuvant chemotherapy or radiation therapy for breast cancer. This health-promoting self-care activity needs further testing in large randomized clinical trials.", "A first breast cancer recurrence creates considerable distress, yet few psychosocial interventions directed at this population have been reported. The Southwest Oncology Group conducted a phase III randomized trial to evaluate the effectiveness of a brief telephone intervention.\n Three hundred five women experiencing a first recurrence of breast cancer were randomly assigned to standard care or intervention. The intervention consisted of four to eight telephone calls delivered over a 1-month period. The calls were conducted by trained peer counselors at a breast cancer advocacy organization, the Y-ME National Breast Cancer Organization, and followed a standard curriculum. Psychosocial distress (Cancer Rehabilitation Evaluation System-Short Form [CARES-SF]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) outcomes were assessed at baseline and 3 and 6 months. The 3-month assessment was the primary end point and is the focus of this article.\n Analysis revealed no differences in distress or depressive symptoms at 3 months between the intervention and control groups; at 3 months, 70% of control patients and 66% of intervention patients reported psychosocial distress, and 40% of control patients and 47% of intervention patients exhibited depressive symptoms.\n Telephone peer counseling did not lead to better psychosocial outcomes. The persistent distress in these women supports the urgent need for the development and testing of more intensive or different supportive interventions for this group of patients.", "Fatigue is a frequent problem after surgical treatment of solid tumours. Aerobic exercise and psychosocial interventions have been shown to reduce the severity of this symptom in cancer patients. Therefore, we compared the effect of the two therapies on fatigue in a randomised controlled study. Seventy-two patients who underwent surgery for lung (n=27) or gastrointestinal tumours (n=42) were assigned to an aerobic exercise group (stationary biking 30 min five times weekly) or a progressive relaxation training group (45 min three times per week). Both interventions were carried out for 3 weeks. At the beginning and the end of the study, we evaluated physical, cognitive and emotional status and somatic complaints with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module (EORTC-QLQ-30) questionnaire, and maximal physical performance with an ergometric stress test. Physical performance of the training group improved significantly during the programme (9.4+/-20 watts, p=0.01) but remained unchanged in the relaxation group (1.5+/-14.8 watts, p=0.37). Fatigue and global health scores improved in both groups during the intervention (fatigue: training group 21%, relaxation group 19%; global health of both groups 19%, p for all < or =0.01); however, there was no significant difference between changes in the scores of both groups (p=0.67). We conclude that a structured aerobic training programme improves the physical performance of patients recovering from surgery for solid tumours. However, exercise is not better than progressive relaxation training for the treatment of fatigue in this setting.", "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." ]

[ "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" ]

[ "7447362", "3046651", "11236113", "8238130", "8238160", "1303479", "2880755", "8116706", "18472878", "8051377", "2147500", "8245589", "395814", "3186087", "14526317", "1407911", "9699761" ]

[ "Prophylactic antibiotics in Caesarean section: effect of a short preoperative course of benzyl penicillin or clindamycin plus gentamicin on postoperative infectious morbidity.", "A double-blind randomized controlled trial on the use of prophylactic antibiotics in patients undergoing elective caesarean section.", "A randomised controlled trial of antibiotic prophylaxis in elective caesarean delivery.", "Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.", "Randomized trial of prophylactic antibiotic therapy after preterm amnion rupture.", "The role of prophylactic antibiotics in caesarean section--a randomised trial.", "Prevention of postoperative infection in cesarean section after rupture of the membranes.", "A prospective, randomized, placebo-controlled trial of penicillin in preterm premature rupture of membranes.", "Randomized trial of antibiotics in addition to tocolytic therapy to treat preterm labor.", "[Antibiotic prophylaxis in a priori cesarean sections without a high risk of infection. Experiences of a Tunisian maternity department].", "[Antibiotic prophylaxis in cesarean sections without high risk of infection. Therapeutic trial of cefotetan versus placebo].", "[The efficacy of prophylactic antibiotic and tocolytic therapy for premature rupture of the membranes--a prospective randomized study].", "Group B streptococcal colonization of pregnant women and their neonates. Epidemiological study and controlled trial of prophylactic treatment of the newborn.", "A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection.", "Duration of antibiotic therapy after preterm premature rupture of fetal membranes.", "Expectant management of preterm ruptured membranes: effects of antimicrobial therapy.", "A randomized trial of three antibiotic regimens for the treatment of pyelonephritis in pregnancy." ]

[ "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.", "In a double-blind randomized controlled study 232 patients undergoing elective lower segment caesarean section were randomly allocated to receive a pre-operative prophylactic dose of a combination of crystalline penicillin and chloramphenicol or a placebo. The two groups were comparable in terms of patient characteristics and operation variables. The group receiving antibiotics had significantly fewer febrile and infectious morbid events and thus spent fewer days in hospital than the group receiving the placebo.", "To determine whether prophylactic antibiotic administration using cefoxitin at the time of elective caesarean section significantly reduces infectious morbidity.\n A tertiary teaching hospital in a large urban city in South Africa.\n Women undergoing elective caesarean section.\n A prospective, double-blind randomised placebo-controlled trial.\n Four hundred and eighty women undergoing elective caesarean section had cefoxitin or placebo administration after umbilical cord clamping. Postpartum complications including febrile morbidity, wound infection, endometritis, urinary tract infection, pneumonia and transient postpartum fever were recorded, as were the duration of hospital stay and the need for therapeutic antibiotics.\n Wound infection was the most common complication occurring in 13.3% and 12.5% of women in the placebo and cefoxitin groups, respectively. Prophylactic antibiotics did not decrease febrile morbidity, wound infection, endometritis, urinary tract infection and pneumonia. Women who received cefoxitin stayed on average a day less in hospital than those who received placebo (6.9 vs 7.8 days, risk difference 0.94 CI 1.57 - 0.31 days). Eleven women (4.6%) in the placebo group and eight (3.4%) in the cefoxitin group had microbiological evidence of wound infection. Staphylococcus aureus was the most common pathogen (43%) isolated. Similar proportions in both groups (6.3% placebo and 5.1% cefoxitin) required a course of therapeutic antibiotics.\n Antibiotic prophylaxis with cefoxitin in elective caesarean section did not reduce post-operative infectious morbidity in this double-blind randomised placebo controlled trial.", "Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes.\n A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos.\n Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization.\n The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.", "Our purpose was to determine whether maternal administration of prophylactic ampicillin or erythromycin after preterm amnion rupture is associated with maternal or neonatal benefits.\n Women with singleton pregnancies between 24 and 33 weeks 6 days of gestation were eligible if they had no immediate indication for delivery. After giving informed consent, patients were randomized either to receive ampicillin (erythromycin if penicillin allergic) until delivery or to enter a control group. Women whose cervical cultures were positive for either group B streptococci or Neisseria gonorrhoeae received treatment. Tocolytics and corticosteroids were not used.\n From January 1990 to February 1992 117 patients (antibiotics 59, control 58) were recruited and analyzed. Prophylactic antibiotics were associated with a longer latent phase (mean 12 vs 7.0 days, p = 0.004) and fewer maternal infectious complications (29% vs 60%, p = 0.001). A higher incidence of neonatal necrotizing enterocolitis was observed in the treatment group (14% vs 3.5%, p = 0.05). Other neonatal complications, including death, were lower in the treatment group, but none attained statistical significance (p = 0.09 to 0.33).\n The use of prophylactic antibiotics in selected patients after preterm amnion rupture appears to have a demonstrable maternal benefit. Large, multicenter trials may demonstrate a significant neonatal benefit or confirm any adverse outcomes.", "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.", "Patients having a cesarean section more than 6 h after rupture of the membranes constitute a high risk group for postoperative infections. Two such groups were studied. Patients were given either cefuroxime 1.5 g every 8th hour for 24 h followed by cefadroxil 0.5 g twice daily for 6 days or received no medication. The infection rate was significantly reduced in the treatment group as compared to the control group (15% vs. 48%). Non-infected patients had a significantly shorter stay in hospital (8 days vs. 12 days). Combined use of these drugs for prevention of post-cesarean infection has not previously been reported. No side effects of the antibiotic prophylaxis were reported.", "Preterm premature rupture of the fetal membranes is common and frequently results in infectious complications. A prospective, randomized, controlled trial of penicillin versus placebo in preterm premature rupture of membranes is reported. The aim of the study was to determine if prophylactic antibiotics after preterm premature rupture of membranes would reduce infectious complications in the mother or neonate.\n Patients with preterm premature rupture of membranes between 21 and 37 weeks' gestation were randomized into a penicillin group that received 1 million units of benzylpenicillin intravenously every 4 hours followed by 250 mg of potassium phenoxymethyl penicillin (Pen-Vee K, Wyeth-Ayerst) orally twice daily or a placebo group before delivery. Latency period, infectious complications, and neonatal outcomes were studied.\n Patients with preterm premature rupture of membranes who received prophylactic penicillin had fewer infectious complications, including intraamniotic infection and postpartum endometritis (4 vs 11, p < 0.03), without adverse effects on the mother or fetus.\n Prophylactic penicillin in patients with preterm premature rupture of membranes reduces maternal infectious complications without adversely affecting the mother or newborn.", "The objective of this study was to assess whether antibiotic therapy plus tocolysis given to women in preterm labor would prolong pregnancy compared with tocolysis alone.\n A randomized, double-blind trial of intravenous mezlocillin and oral erythromycin therapy vs. placebo was used in addition to tocolysis among women in preterm labor < or =34 weeks gestation with intact membranes. Amniocentesis was performed, and chorioamnionic membranes were examined histologically and cultured for microorganisms after delivery.\n Clinical characteristics including gestational age at enrollment, frequency of contractions, cervical Bishop's score, and white blood cell count on admission were similar in the 2 groups. Antibiotic therapy was well tolerated. No significant differences in the interval to delivery, birth weight, and neonatal outcomes were observed between the 2 groups. Women in the antibiotic group had a significantly lower incidence of postpartum infections compared with women in the placebo group. Patients with evidence of upper genital tract infection in either group had a significantly shorter interval to delivery, lower gestational age at delivery, lower mean birth weight, and increased neonatal hospitalization time.\n Lack of an antibiotic effect on the gestational age at delivery may be due to the low prevalence of upper genital tract infection among unselected women in preterm labor, to advanced preterm labor unresponsive to antibiotic therapy, or to an inability of antibiotics given alone to inhibit the cytokine response. Further work is needed to identify markers of upper genital tract infection among women in preterm labor and to evaluate other potential therapeutic interventions.", "This study was conducted to evaluate the effect of antibiotic prophylaxy on decreasing the frequency of postoperative infections after cesarean sections performed in cases with no prior indication of a high risk of infection.\n A prospective randomized study included 269 cesarean sections without a high risk of infection performed in the Maternity and Neonatology Ward of the Sousse Hospital from February 1991 to July 1991. The patients were randomly divided into two groups. One group received an antibiotic prophylactic treatment including cephapirine, gentamicin and metronidazole) and the second group was given no treatment.\n Antibiotic prophylactic therapy led to a reduction of infectious morbidity after cesarean section in patients without high risk o infection from 33% to 11%. A 66% rate of efficacy was observed. In addition, antibiotics given in this context led to substantial cost reduction both by reducing the cost of antibiotics prescribed in the postoperative period and by reducing the number of days of hospitalization, and thus total cost.\n This study demonstrated the effectiveness of antibiotic prophylaxy for cesarean sections in patients without a high risk of infection. Nevertheless, a reevaluation of the antibiotic protocols and a rigorous operative procedure are essential.", "Caesarean sections are performed with an ever increasing frequency, and their morbidity rate due to infection varies between 35 and 40 per cent. The effectiveness of antibiotic prophylaxis has been demonstrated in caesarean sections with a high risk of infection, but few studies have been devoted to caesarean sections without this high risk. The purpose of our study was to evaluate the effectiveness of antibiotic therapy in this second type of caesarean section since its postoperative infection rate is not negligible (about 25 per cent). We therefore set up a two-centre randomized trial comparing two groups of 133 women without any particular risk of infection. At the moment of umbilical cord clamping, one group received cefotetan 1 g intravenously, while the other group received an intravenous injection of a placebo solution. The postoperative infection rate was 12.5 per cent in the treatment group and 26.9 per cent in the control group (P less than 0.05). The relative risk in the placebo-treated women was 2.15 (95 per cent confidence limits, 1.41 to 3.28). Antibiotic prophylaxis prevented 53.5 per cent of postoperative infections (95 per cent confidence limits, 29 to 69.5 per cent). Moreover, in the treatment group infections were less severe, resulting in a significant decrease in hospital stay and a lower overall cost. We conclude that antibiotic prophylaxis with cefotetan is effective in caesarean sections without a high risk of infection, as it significantly reduces the postoperative morbidity due to infection.", "A comparative study in patients with premature rupture of the membranes (PROM) from 25 to 34 weeks of gestation was carried out, prospectively. Group 1 (34 patients) was given aggressively intrauterine therapy including the administration of tocolytic agents (ritodrine and/or magnesium sulfate) and prophylactic antibiotics (AB-PC 2g/day). Group 2 (41 patients) was managed conservatively with bed rest only. At the time of admission to the study, there were no clinical signs of infection, fetal distress, or active labor in either group. All patients were delivered if the pregnancy had reached 35 weeks of gestation or later, had established labor, or developed evidence of chorioamnionitis or fetal distress. Prolongation for more than 72 hours was greater in group 1 than in group 2. There was no difference in the incidence of chorioamnionitis, postpartum endometritis, or placental infection in the groups. However, the incidence of a low Apgar score (7 < at 5 min), requiring artificial ventilation, and infection was more common in group 1. It is concluded that the use of antibiotics and tocolytics might make the management of PROM more complicated.", "Colonization with group B streptococci of the genital tract was studied in 1 115 women during the last trimester of pregnancy. 76 or 6.82% were found to harbour this bacterium. The incidence of contamination was significantly higher among Belgian women than among parturients of Mediterranean origin (p less than 0.001). It was also more frequent in primigravidae (p less than 0.05) and in the poorer (0.10 less than p greater than 0.05). At the time of admission in the delivery room, it was noticed that rupture of the amniotic membranes for more than 24 hours was more often associated with group B streptococcal carriage by the mother (p less than 0.001). 29 out of 68 (42.6%) infants born to group B streptococci positive mothers were colonized at birth. 67 of them were submitted to a controlled trial of immediate versus delayed penicillin therapy. 44.8% and 42.1% of the neonates were contaminated at birth in each group of treatment respectively. No instance of group B streptococcal infection developed in either group. This suggests that immediate therapy with penicillin of infants of group B streptococci positive mothers has no definite advantage upon delayed treatment.", "A randomized trial of intrapartum versus postpartum antibiotic treatment of women with intra-amniotic infection was conducted. Intra-amniotic infection was treated with ampicillin and gentamicin during labor (at the time of diagnosis) in 26 women and immediately after umbilical cord clamping in 19 women. Intrapartum treatment led to a lower incidence of neonatal sepsis (0 versus 21%; P = .03) and a shorter neonatal hospital stay (3.8 versus 5.7 days; P = .02) when compared with postpartum treatment. There were no significant differences in the microbiologic results, the gestational age, or the birth weight between the groups. Intrapartum-treated mothers had a shorter mean postpartum stay, a lower mean number of febrile days, and a lower mean peak postpartum temperature than did postpartum-treated mothers; these differences were all statistically significant (P = .05). The treatment of clinical intra-amniotic infection during labor results in improved outcome.", "This study was undertaken to compare the efficacy of 3 days versus 7 days of ampicillin in prolonging gestation for at least 7 days in women with preterm premature rupture of membranes (PPROM).\n We performed a randomized clinical trial comparing 3 days of ampicillin with 7 days ampicillin in patients with PPROM. Our primary outcome was the prolongation of pregnancy for at least 7 days. Secondary outcomes included rates of chorioamnionitis, postpartum endometritis, and neonatal morbidity and mortality.\n Forty-eight patients were randomly selected. There was no statistically significant difference in the ability to achieve a 7-day latency (relative risk 0.83, 95% CI 0.51-1.38). In addition, there was no statistically significant difference in the rates of chorioamnionitis, endometritis, and our composite neonatal morbidity.\n In patients with PPROM, length of antibiotic therapy does not change the rate of a 7-day latency or affect the rate of chorioamnionitis, postpartum endometritis, or neonatal morbidity.", "To determine whether the addition of broad-spectrum antimicrobial therapy to traditional expectant management improves pregnancy outcome in patients with premature rupture of membranes (PROM) remote from term.\n Patients with preterm PROM before 34 weeks' gestation who were not in labor and had no signs of infection or fetal distress were randomized to one of two study groups: 1) expectant management alone and 2) expectant management plus antimicrobial therapy. Women in the latter group received intravenous ampicillin, gentamicin, and clindamycin for 24 hours, followed by amoxicillin plus clavulanic acid orally for 7 days. Other than antibiotic use, management of the two groups was identical.\n Significantly more women (P < .01) treated with antibiotics (20 of 48, 42%) remained undelivered 7 days after admission compared with those managed expectantly without antibiotics (seven of 46, 15%). In addition, more neonates in the group managed with antibiotics were admitted to the routine nursery (nine of 48 versus two of 45; P = .03). However, there was no difference between the groups in the frequency of serious maternal or neonatal morbidity.\n The addition of broad-spectrum antimicrobial therapy to traditional expectant management of pregnancy complicated by preterm PROM may increase the number of gestations undelivered 7 days after admission. It may also decrease the proportion of infants admitted to special care nurseries. Whether these effects result in significant short- or long-term maternal or neonatal benefit remains to be determined.", "To compare the effectiveness of three antibiotic regimens for the treatment of acute pyelonephritis in pregnancy.\n One hundred seventy-nine pregnant women earlier than 24 weeks' gestation who had acute pyelonephritis were randomized to 1) intravenous (i.v.) ampicillin and gentamicin, 2) i.v. cefazolin, or 3) intramuscular ceftriaxone. All participants then completed 10-day courses of oral cephalexin after primary treatment. A urine culture was performed on admission and 5-14 days after completion of therapy. Surveillance for persistent or recurrent infection and obstetric complications continued until delivery. On the basis of a two-sided hypothesis test and with alpha = .025, 60 subjects were needed in each group for statistical power greater than 80% to detect a difference between ceftriaxone and other antibiotics if hospital length of stay differed by 1 or more days.\n The treatment groups were similar in age, parity, temperature, gestational age, and initial white blood cell count. There were no statistically significant differences in length of hospitalization, hours until becoming afebrile, days until resolution of costovertebral angle tenderness, or infecting organism. There were no statistically significant differences in birth outcomes between the three groups. The average (standard deviation) age at delivery was 38.8 +/- 3.6 weeks. The average birth weight was 3274 +/- 523 g. Eleven (6.9%) of 159 subjects delivered prematurely. Escherichia coli was the most common uropathogen isolated (137 of 179, 76.5%). Blood cultures were positive for organisms in 15 cases (8.4%). At follow-up examination within 2 weeks of initial therapy, eight (5.0%) of 159 subjects had urine cultures positive for organisms. Ten women (6.3%) had cultures positive for organisms later in their antepartum course, and 10 other participants (6.3%) developed recurrent pyelonephritis.\n There are no significant differences in clinical response to antimicrobial therapy or birth outcomes among subjects treated with ampicillin and gentamicin, cefazolin, or ceftriaxone for acute pyelonephritis in pregnancy before 24 weeks' gestation." ]

[ "12193488", "3524668", "9252001", "8110580", "3266072", "8379864", "3538985", "7917733", "9758071", "12535037" ]

[ "Iliohypogastric-ilioinguinal peripheral nerve block for post-Cesarean delivery analgesia decreases morphine use but not opioid-related side effects.", "Pain relief in labour using transcutaneous electrical nerve stimulation (TENS). A TENS/TENS placebo controlled study in two parity groups.", "Transcutaneous nerve stimulation (TENS) during the first stage of labour: a randomized clinical trial.", "Comparison of the effectiveness of bilateral ilioinguinal nerve block and wound infiltration for postoperative analgesia after caesarean section.", "An evaluation of transcutaneous electrical nerve stimulation for pain relief in labour.", "Abdominal nerve blockade for postoperative analgesia after caesarean section.", "Transcutaneous electrical nerve stimulation following appendicectomy: the placebo effect.", "Multimodal analgesia before thoracic surgery does not reduce postoperative pain.", "Analysis of peak magnitude and duration of analgesia produced by local anesthetics injected into sympathetic ganglia of complex regional pain syndrome patients.", "A comparison between local anaesthetic dorsal nerve block and caudal bupivacaine with ketamine for paediatric circumcision." ]

[ "To examine if ilioinguinal-iliohypogastric nerve block could reduce the need for post-Cesarean delivery morphine analgesia and thus reduce the incidence of opioid related adverse-effects.\n A multi-level technique for performing the nerve block with bupivacaine was developed and then utilized in this two-part study. Part one was a retrospective assessment of Cesarean delivery patients with and without ilioinguinal-iliohypogastric blocks to determine if the technique reduced patient controlled analgesia morphine use and thus would warrant further study. The second phase was a randomized double-blind placebo-controlled trial to compare post-Cesarean morphine use and the appearance of opioid-related side effects between the anesthetic and placebo-injected groups.\n Both phases demonstrated that our method of ilioinguinal-iliohypogastric nerve block significantly reduced the amount of iv morphine used by patients during the 24 hr following Cesarean delivery. In the retrospective assessment, morphine use was 49 +/- 30 mg in the block group vs 79 +/- 25 mg in the no block group (P = 0.0063). For the prospective trial, patients who received nerve blocks with bupivacaine had a similar result, self-administering 48 +/- 27 mg of morphine over 24 hr compared to 67 +/- 28 mg administered by patients who received infiltrations of saline. However, despite the significant decrease in morphine use, there was no reduction in opioid-related adverse effects: the incidences of nausea were 41% and 46% (P = 0.70) and for itching were 79% and 63% (P = 0.25) in the placebo and nerve block groups, respectively.\n A multi-level ilioinguinal-iliohypogastric nerve block technique can reduce the amount of systemic morphine required to control post-Cesarean delivery pain but this reduction was not associated with a reduction of opioid related adverse effects in our study group.", "The analgesic effects of transcutaneous electrical nerve stimulation (TENS) in labour and effects on outcome were investigated in a double-blind TENS/TENS placebo controlled trial in 100 primigravidae and 50 women in their third labour. There were no differences between the TENS and the TENS placebo users in terms of pain concept or relief, and only 12 and 13% of primigravidae and 48 and 39% of the para 2 women completed labour without requiring other analgesia in their respective groups. The primigravidae who used either TENS or TENS placebo alone had shorter labours than those who required further analgesia. Although the outcome of labour for mother and infant were similar in the two groups, there was a higher operative delivery rate in women who also had epidural analgesia. There were highly significant differences between the TENS and the TENS placebo users in terms of favourable and unfavourable comments by the mothers and the midwives at 1 and 24 h after delivery. The evident consumer satisfaction for TENS suggests TENS has a part to play in analgesia in labour but the equivocal findings in terms of factors associated with pain relief points to the need for apparatus more specifically designed to cope with the special characteristics of the pain of labour.", "Our objective was to study the efficacy of transcutaneous electrical nerve stimulation (TENS) in reducing pain during the first stage of labour. Using a prospective randomized placebo-controlled, double blind clinical trial, a patient-controlled analgesia system was used to measure differences in outcome. Trials took place in a labour unit at the St. Antonius Hospital, Nieuwegein, The Netherlands, during a period of 18 months. Forty-six patients, during the first stage of labour, were treated with TENS, and 48 with a placebo apparatus. Main outcome measures were pain relief, amount of administered analgesics, obstetrical and neonatal outcome, and side effects. No significant differences occurred between groups in the number of requests for pethidine/promethazine. The foetal outcome in both groups was the same. TENS and placebo were considered equally effective by both patients and staff. In conclusion, TENS was not more effective than a placebo apparatus in relieving pain during the first stage of labour. No adverse side-effects occurred.", "We have studied the effects of bilateral ilioinguinal nerve block and wound infiltration with 0.5% bupivacaine on postoperative pain and analgesic requirements in 62 patients undergoing Caesarean section under general anaesthesia. A control group received no local anaesthetic supplementation. Both ilioinguinal block and wound infiltration reduced significantly the pain scores and analgesic requirements in the immediate postoperative period (P < 0.05). The differences in pain scores and analgesic requirements between the study groups were not statistically significant (P > 0.05).", "The effectiveness of transcutaneous nerve stimulation (TENS) for pain relief in labour was evaluated by randomizing 280 patients in early labour into 2 groups. Inoperative sham machines were applied to patients in the control group and active units to those in the test group. Neither patients nor attending labour ward staff were aware of which group the patient was in. The intensity of low back pain and abdominal pain was assessed by the patient each hour on a visual analogue pain scale. Each patient served as her own control by switching off the machine for 2 contractions every hour and then recording the intensity of pain. The amount of conventional analgesia each patient received was recorded by labour ward staff. There was no difference in the intensity of pain recorded by each group. Nor was there any difference between the 2 groups in the change of pain experienced when the machine was switched off. Moreover there was no difference in the amount of other analgesia required. Some differences were found when those with little low back pain were excluded from the study. We conclude that TENS is ineffective as a routine method of pain relief in labour. It is likely to benefit only those with severe back pain and then only to a modest degree.", "A prospective study of blocking T10-L1 with local anaesthetic, bilaterally in 30 patients undergoing caesarean section under general anaesthesia has been shown to provide effective postoperative analgesia thus requiring significantly less narcotics (mean 66.6 mg of pethidine) compared to the 30 patients in the control group (mean 163 mg of pethidine). A cocktail of 0.5% of bupivacaine with adrenaline and xylocaine 1% produced analgesia for the duration ranging from 8 to 12 hours (mean 8.4 hours). Patients with abdominal field block were awake, alert and comfortable during the immediate postoperative period. They were pain-free sufficiently to put the babies to the breast early and frequently.", "A controlled trial was undertaken to compare the efficacy of transcutaneous electrical nerve stimulation (TENS) with standard intramuscular opiate analgesia in the management of postoperative pain following appendicectomy. Consecutive patients undergoing emergency appendicectomy were randomised into control, sham TENS and active TENS groups. There was a significant decrease in pain severity and analgesic intake in both active and sham TENS groups when compared with the control group (P less than 0.01). No difference was demonstrated in pain severity between active and sham TENS groups but the active TENS group required slightly less analgesia. These results suggest that the major benefit of TENS in the postappendicectomy patient is due to its 'placebo effect' and its use in this situation cannot be recommended.", "Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain.", "Pain-relieving effects of lidocaine/bupivicaine local anesthetic (LA) and saline (S) block of sympathetic ganglia (stellate block, 4 patients; lumbar sympathetic block, 3 patients) were compared in 7 complex regional pain syndrome (CRPS) patients on a double-blind crossover basis to evaluate the diagnostic and therapeutic value of local anesthetic sympathetic blocks.\n Patients rated their pain on a visual analog scale before and after blocks and were tested for mechanical allodynia one-half hour after blocks. Thereafter, they rated their pain intensity in diaries four times a day for 7 days. Each patient received two blocks, S and LA, and served as his own control.\n Both S and LA injections of sympathetic ganglia produced large reductions in pain intensity in 6 of 7 patients 30 minutes after block. These large reductions were accompanied by the reversal of mechanical allodynia in both S and LA. The mean difference between initial peak reduction in pain intensity produced by saline (68.7%) and active local anesthetic (74.4%) did not approach statistical significance. In striking contrast, the mean duration of pain relief was reliably longer in the case of LA (3 days, 18 hours) as compared with S ( 19.9 hours), a difference that occurred in all 7 patients. In a larger sample of 41 CRPS patients, signs of sympathetic efferent blockade, including Homer' s syndrome or skin surface temperature change, were not predictive of initial peak magnitude of pain relief from sympathetic blockade but were predictive of duration of pain reduction.\n The combination of these results provides evidence that duration of pain relief is affected by injection of local anesthetics into sympathetic ganglia. These results indicate that both magnitude and duration of pain reduction should be closely monitored to provide optimal efficacy in procedures that use local anesthetics to treat CRPS.", "Ketamine has been shown to prolong analgesia produced by caudal local anaesthetic block and is now in common use. This study compares caudal block using bupivacaine/ketamine with dorsal nerve block of the penis.\n Sixty boys undergoing elective circumcision were given either 0.5 ml x kg-1 of bupivacaine 0.15% with ketamine 0.5 mg x kg-1 (n = 30) or dorsal nerve block of the penis with bupivacaine 0.5% (n = 30) as a supplement to general anaesthesia. Postoperative pain was assessed by parents using a modified objective pain score, and the time taken to first requirement of analgesia was recorded. Motor weakness, time to first micturition, postoperative nausea and vomiting (PONV), eating habits, sleep disturbance and behaviour were also assessed.\n There was no difference between the groups in time to first requirement for analgesia or number of doses of paracetamol given in the first 24 h. Almost half the boys in the caudal group had motor weakness, and there was a significant increase in time to first micturition in that group. There was no difference between the groups in PONV, eating, sleeping or behavioural disturbance.\n Caudal anaesthesia with bupivacaine/ketamine does not confer any advantage over a dorsal nerve block with the doses used in this study. Because of the higher incidence of side-effects and technique failure in the caudal group, dorsal nerve block is perhaps the preferred technique." ]

[ "3044868", "16241013" ]

[ "Analgesic effect of aspirin, mefenamic acid and their combination in post-operative oral surgery pain.", "Randomized controlled trial of mefenamic acid vs paracervical block for relief of pain for outpatient uterine curettage." ]

[ "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.", "To compare the efficacy of mefenamic acid vs paracervical block for pain relief during and after fractional curettage.\n Between January 1 and July 31, 2002, the authors enrolled 87 patients with abnormal uterine bleeding, who requested fractional curettage at the Outpatient Gynecologic Clinic, Srinagarind Hospital, Khon Kaen University. A simple randomization procedure was used to distribute the patients into a control group comprising 44 patients given a paracervical block and a treatment group comprising 43 patients given mefenamic acid (500 mg) 2 hours before starting the procedure.\n Pain was scored using a visual analogue scale (VAS range, 0 to 10).\n The median pain scores of the treatment types during endocervical, endometrial, immediately after, and 30 minutes after, fractional curettage were 2.5 vs 3.0 (p = 0.42), 6.5 vs 7.5 (p = 0.19), 4.0 vs 3.5 (p = 0.20) and 1.5 vs 1.0 (p = 0.17), respectively. The rate of complications was 6.8% (3 in 44) in the paracervical lignocaine injection group.\n The efficacy of pain relief for fractional curettage using oral mefenamic acid (500 mg) two hours before the procedure was not statistically different from the paracervical block, but there were fewer side effects. Mefenamic acid should be considered an alternate pain relief during fractional curettage." ]

[ "21125215", "10092916", "7710151", "2569600", "12040756" ]

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

[ "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.", "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.", "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.", "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.", "Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain.\n Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neuropsychological test at 3 months without treatment in that period and started HBO thereafter.\n All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance.\n HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement." ]

[ "11890637", "15113965", "10721929", "11053509", "12164031", "12354473", "17928808", "11814373", "8816034", "10989766", "7992349", "11044264", "16630383", "15566454", "538502", "19430082", "9310602" ]

[ "Will iron supplementation given during menstruation improve iron status better than weekly supplementation?", "Daily iron supplementation is more efficacious than twice weekly iron supplementation for the treatment of childhood anemia in western Kenya.", "Efficacy and acceptability of two iron supplementation schedules in adolescent school girls in Lima, Peru.", "Daily iron supplementation is more effective than twice weekly iron supplementation in pregnant women in Pakistan in a randomized double-blind clinical trial.", "Intermittent oral iron supplementation during pregnancy.", "Intermittent administration of iron and sulfadoxine-pyrimethamine to control anaemia in Kenyan children: a randomised controlled trial.", "The effect of weekly iron and vitamin A supplementation on hemoglobin levels and iron status in adolescent schoolgirls in western Kenya.", "Weekly vs daily iron and folic acid supplementation in adolescent Nepalese girls.", "Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani Division, Tanzania.", "Effect of daily and intermittent iron supplementation on iron status of high school girls.", "The effects of iron supplementation during pregnancy, given by traditional birth attendants, on the prevalence of anaemia and malaria.", "Micronutrient and iron supplementation and effective antimalarial treatment synergistically improve childhood anaemia.", "Failure of twice-weekly iron supplementation to increase blood haemoglobin and serum ferritin concentrations: results of a randomized controlled trial.", "Daily versus intermittent iron supplementation in pregnant women: hematological and pregnancy outcome.", "Iron supplementation studies among pregnant women.", "Physical work capacity of young underprivileged school girls impact of daily vs intermittent iron folic acid supplementation: a randomized controlled trial.", "Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants." ]

[ "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 recent meta-analysis of 14 clinical trials indicated that daily compared with intermittent iron supplementation resulted in significantly greater hematological improvement in pregnant women. No such definitive beneficial effect was demonstrated in preschool children. We compared the efficacy of daily and twice weekly iron supplementation for 6 wk under supervised and unsupervised conditions in the treatment of mild and moderate anemia [hemoglobin (Hb) 50-109 g/L] in children aged 2-59 mo living in a malaria-endemic area of western Kenya. The study was a cluster-randomized trial using a factorial design; participants were aware of the treatment assigned. All children (n = 1049) were administered a single dose of sulfadoxine-pyrimethamine at enrollment followed by 6 wk of daily supervised iron supplementation [3-6 mg/(kg.d)], twice weekly supervised iron supplementation [6-12 mg/(kg.wk)], daily unsupervised iron supplementation, or twice weekly unsupervised iron supplementation. In the supervised groups, Hb concentrations at 6 and 12 wk (6 wk postsupplementation) were significantly higher in children given iron daily rather than twice weekly [mean (95% CI) difference at 6-wk: 4.2 g/L (2.1, 6.4); 12-wk: 4.4 g/L (1.8, 7.0)]. Among the unsupervised groups, Hb concentrations were not different at 6 wk [mean (95% CI) difference: 0.86 g/L (-1.4, 3.1)], but significantly higher at 12 wk for those assigned daily iron [mean (95% CI) difference: 3.4 g/L (0.79, 6.0), P = 0.02]. In this malarious area and after initial antimalarial treatment, 6 wk of daily iron supplementation results in better hematological responses than twice weekly iron supplementation in the treatment of anemia in preschool children, regardless of whether adherence can be ensured.", "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.", "In the context of limited effectiveness of iron supplementation programs, intermittent iron supplementation is currently under debate as a possible alternative strategy that may enhance the effectiveness of operational programs. This field-based trial assessed the outcome of twice weekly iron supplementation compared to daily in Pakistan. A double-blind, randomized, clinical trial was conducted in Northern Pakistan. Anemic pregnant women (n = 191) were assigned to receive daily (200 mg ferrous sulfate) or twice weekly (2 x 200 mg ferrous sulfate) iron supplementation. Hemoglobin was measured at baseline and at 4-wk intervals for up to 12 wk. Serum ferritin was measured at baseline and 8 or 12 wk. Analysis was by intention to treat. The two groups did not differ in age, parity, sociodemographic characteristics, hemoglobin or serum ferritin concentrations at baseline. Women who received iron daily had a greater rise in hemoglobin compared with women who received iron twice weekly (17.8 +/- 1.8 vs. 3.8 +/- 1.2 g/L, P < 0.001). The serum ferritin concentrations increased by 17.7 +/- 3.9 microgram/L (P < 0.001) in the daily supplemented group and did not change in the twice weekly group. Daily iron supplementation remained superior to twice weekly supplementation after controlling initial hemoglobin Z-scores and duration of treatment. The body mass index (BMI) modified the effect of daily versus twice weekly iron supplementation. For every unit increase in BMI, the difference between the two treatment groups was reduced by 0.0014 (final hemoglobin Z-score; P = 0.027). We recommend continuation of daily iron supplementation as opposed to intermittent iron supplementation in pregnant women in developing countries.", "It has been suggested that in pregnant women weekly iron supplements are as effective as daily supplements in preventing iron deficiency anaemia (IDA).\n To compare the effectiveness of prophylactic antenatal oral iron supplements given weekly, thrice weekly and daily in preventing IDA in pregnancy.\n A randomised control trial.\n University antenatal clinic, (UANC) Galle.\n An oral iron supplement containing 100 mg of elemental iron was randomly given weekly (n = 26) thrice weekly (n = 35) and daily (n = 31) to 92 women who were 14 to 24 weeks pregnant. Haemoglobin (Hb), serum ferritin (SF) and haematocrit (Hct) were assessed before and after 12 to 20 weeks of supplementation and a logistic regression analysis carried out.\n The risk of developing anaemia was significantly higher in the weekly (odds ratio 15, 95% CI 1.4-165.6, p < 0.03) and possibly higher in the thrice weekly (odds ratio 3, 95% CI 0.3-30.3, p = 0.3) groups. The risk of developing iron deficiency (SF < 12 micrograms/l) was also significantly higher in the weekly (odds ratio 18, 95% CI 2.8-115.5, p < 0.003) and thrice weekly (odds ratio 10, 95% CI 1.6-64.8, p < 0.02) groups.\n Prophylactic oral iron supplements when given intermittently were not effective in preventing iron deficiency anaemia in pregnancy.", "Iron supplementation is recommended for children at high risk of anaemia, but its benefits may not outweigh the associated risk of malaria in areas of seasonal transmission. We investigated the effect on haemoglobin concentrations of intermittent administration of iron supplements and sulfadoxine-pyrimethamine in symptom-free children under intense health surveillance.\n In a trial of two by two factorial design, 328 anaemic Kenyan children were randomly assigned either iron or placebo and sulfadoxine-pyrimethamine or placebo (82 to each group). Primary outcomes were haemological indicators of iron status and inflammation at the end of the follow-up, and occurrence of malaria attacks. Morbidity surveillance consisted of medical examinations every 4 weeks, continuous passive case detection, and visits twice a week to community health-workers. Analyses were by intention to treat.\n After 12 weeks, the groups assigned iron plus sulfadoxine-pyrimethamine, iron alone, or sulfadoxine-pyrimethamine alone had higher haemoglobin concentrations than the group assigned placebo (treatment effect adjusted for prognostic factors at baseline: 11.1 g/L [95% CI 7.5 to 14.7]; 10.7 g/L [7.1 to 14.3]; and 3.1 g/L [-0.5 to 6.7]). Administration of iron plus sulfadoxine-pyrimethamine also lowered the proportion with anaemia from 100% at baseline to 36% at 12 weeks, and of iron deficiency from 66% at baseline to 8% at 12 weeks. Survival analysis showed no evidence of substantially increased risk of malaria after iron supplementation.\n Iron supplementation gives substantial health benefits, which may outweigh possible inherent risks caused by malaria. A larger study than ours is needed to assess benefits and risks of intermittent administration of sulfadoxine-pyrimethamine in reducing the incidence of malaria attacks in areas of seasonal malaria transmission.", "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.", "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.", "Oral iron supplementation is often routinely given to children with malaria-associated anaemia, but its contribution to recovery is controversial. A randomized clinical trial, evaluating such routine, was carried out among 100 children, who had a haemoglobin of < or = 5 g/dl and a positive blood smear for malaria parasites. All children received malaria therapy (chloroquin + fansidar) and were randomly allocated to two groups, one receiving additional oral iron treatment, the other being the control. In the 12-week follow-up period the haemoglobin level and malaria indices were measured at 2, 4, 8, and 12 weeks. There was a 100 per cent compliance during the follow-up period. In each group 20 children (40 per cent) required a blood transfusion. In the remaining 60 children, after 2 weeks the haemoglobin had risen 3.7 g/dl in the ferrous-supplemented group compared to 3.5 g/dl in the non-ferrous group. Thereafter, the increase in haemoglobin in both groups was steady. At follow-up measurements, the groups did not differ for haemoglobin levels. The mean haemoglobin at 12 weeks was 9.2 and 9.0 g/dl, respectively. It was concluded that iron supplementation did not have any effect on the rate of parasitaemia and on parasite density during the 12 weeks. However, the iron-supplemented group had a significantly increased morbidity from other causes than malaria. It appears that iron does not have an effect on the recovery of haemoglobin level in children with malaria-associated anaemia. This study provides no evidence supporting routine iron supplementation to these children.", "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.", "A randomized, double-blind, placebo-controlled community-based trial of oral iron supplementation (200 mg ferrous sulphate daily) administered to multigravid pregnant women by traditional birth attendants (TBAs) was carried out in a rural area of The Gambia. Iron supplementation led to a significant reduction in the prevalence of anaemia and of iron deficiency. Iron supplementation was not accompanied by increased susceptibility to malaria infection; there was no difference in the prevalence and severity of peripheral blood or placental malaria infection between the 2 groups of women. The birth weight of children born to women who received iron prophylaxis was increased by an average of 56 g. It is concluded that oral iron prophylaxis can be successfully delivered through TBAs integrated into a primary health care programme. This simple intervention can produce significant beneficial effects on the health of the mother without inducing increased susceptibility to malaria and has the potential for reducing perinatal mortality by increasing birth weight.", "The control of childhood anaemia in malaria holoendemic areas is a major public health challenge for which an optimal strategy remains to be determined. Malaria prevention may compromise the development of partial immunity. Regular micronutrient supplementation has been suggested as an alternative but its effectiveness remains unsettled. We therefore conducted a randomised placebo-controlled intervention trial with 207 Tanzanian children aged 5 months to 3 years on the efficacy of supervised supplementation of low-dose micronutrients including iron (Poly Vi-Sol with iron) three times per week, with an average attendance of >/= 90%. The mean haemoglobin (Hb) level increased by 8 g/l more in children on supplement (95% CI 3-12) during the 5-month study. All age groups benefited from the intervention including severely anaemic subjects. The mean erythrocyte cell volume (MCV) increased but Hb in children >/= 24 months improved independently of MCV and no relation was found with hookworm infection. The data therefore suggest that micronutrients other than iron also contributed to Hb improvement. In the supplement group of children who had received sulfadoxine-pyrimethamine (SP) treatment, the mean Hb level increased synergistically by 22 g/l (95% CI 13-30) compared to 7 g/l (95% CI 3-10) in those without such treatment. Supplementation did not affect malaria incidence. In conclusion, micronutrient supplementation improves childhood anaemia in malaria holoendemic areas and this effect is synergistically enhanced by temporary clearance of parasitaemia.", "In order to increase the intestinal absorption of iron whilst simultaneously minimising the side-effects and thus increasing compliance, once- or twice-weekly, instead of daily, iron supplementation has been widely recommended. In a randomized, placebo-controlled, double-blind study in western Kenya, a tablet of ferrous dextran (containing 60 mg elemental iron) or an identical-looking placebo tablet was provided twice-weekly for 12 months to each child or adult investigated. At baseline each subject had a moderately low blood concentration of haemoglobin (Hb). Initial Hb and serum ferritin (SF) concentrations were determined and each subject was tested for malarial and helminth infection and treated, if necessary, with the appropriate anthelminthic drug(s). Overall, 200 children (aged 4-15 years) and 129 adults (aged 16-63 years) completed the 12-month study. At baseline, 47.5% of the children and 58.1% of the adults were anaemic, hookworm (detected in 60.0% of the children and 69.9% of the adults) was the most common helminth infection, and malaria was endemic. The results of bivariate analyses indicated that twice-weekly iron supplementation had no significant effect on blood Hb or SF concentrations, either in the children or the adults investigated. The results were confirmed in multiple linear-regression analyses, which revealed that the predictors of the final Hb concentration in the children investigated were age and infection, after enrollment, with Ascaris lumbricoides. Gender and the serum concentration of alpha-1-antichymotrypsin (ACT) at final follow-up were predictors of the final SF concentration in the children. In adults, the predictors of the final Hb concentration were gender and HIV infection, and the predictors of the final SF concentration were age and the serum concentration of ACT at the final follow-up. Twice-weekly iron supplementation did not increase Hb or iron stores in children or adults. Since compliance appeared to be high, this lack of effect may be the result of an inadequate dose of iron or of subjects who have deficiencies in micronutrients other than iron.", "To compare the hematological parameters and pregnancy outcome in women receiving daily versus weekly iron supplements during pregnancy.\n A prospective randomized controlled study was carried out at the Department of Obstetrics and Gynaecology of the All India Institute of Medical Sciences, New Delhi, India, during which 111 women were randomized to receive either 100 mg elemental iron daily (n=55) or 200 mg elemental iron weekly (n=56). Hemogram and serum ferritin level estimation were carried out at the beginning of pregnancy and within the 32-34-week period of gestation. Side-effects, compliance and the number of tablets consumed were noted for each group. The mean birth weight, period of gestation at delivery and mode of delivery were also compared between the two intervention groups.\n There was no significant difference in the mean hemoglobin levels between the two intervention groups at the end of an average 17 weeks of iron supplementation. However, among anemic women who received daily supplementation, there was a greater rise in hemoglobin compared with those receiving supplementation weekly. The serum ferritin level was lower in the weekly supplemented group compared with that in the daily. There was no difference in the mean birth weight, period of gestation and mode of delivery between the two groups. Side-effects and non-compliance were significantly higher (P<0.001) in the daily supplemented group.\n Weekly iron supplementation is an effective option for prophylaxis in non-anemic pregnant women, but has less than optimal benefit in anemic women.", "The effect of iron supplementation alone or in combination with ascorbic acid as a preventive and or corrective measure against anemia were tested using pregnant women seeking pre-natal consultation at various health centers in Greater Manila Area. One tablet containing 65 mg iron alone or in combination with ascorbic acid per day during a supplementation period which varied from 16.5 to 17.8 weeks maintained initial hemoglobin and hematocrit levels in non-anemic women. Three tablets of the same iron preparation (total of 195 mg iron) daily resulted in significant increases in hemoglobin and hematocrit in anemic women. Ascorbic acid had no apparent beneficial effect. Considering the positive response to iron treatment, it is recommended that a nationwide program of iron supplementation of pregnant Filipinos be undertaken.", "To assess impact of daily and intermittent iron-folate (IFA) supplementation on physical work capacity of underprivileged schoolgirls in Vadodara.\n Randomized controlled trial.\n Municipal Primary schools.\n Schoolgirls (n=163) in the age group of 9-13 years.\n Three randomly selected schools were given IFA tablets (100 mg elemental iron + 0.5 mg folic acid) either once weekly or twice weekly or daily for one year. The fourth was the control school.\n Hemoglobin, modified Harvards Step test for physical work capacity.\n All three IFA supplemented groups showed significant improvement in number of steps climbed and recovery time compared to controls; with impact being relatively better in girls with higher Hb gain (> 1 g/dL) vs. lower Hb gain. Similarly, higher the frequency of dosing better was the impact- it being the best in daily IFA group. Twice weekly IFA was as good as daily IFA under conditions of good compliance.\n Twice weekly IFA supplementation is comparable to daily IFA in terms of beneficial effects on physical work capacity in young girls.", "Malaria and anaemia, especially that due to iron deficiency, are two leading causes of morbidity worldwide. Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas. We undertook a randomised comparison of different strategies for control of anaemia and malaria in infants, including an assessment of the effect of iron supplementation on malaria susceptibility.\n 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October, 1995, were randomly assigned to group DI, receiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3.125 mg pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus weekly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP. supplementation was given from 8 to 24 weeks of age, and the weekly chemoprophylaxis from 8 to 48 weeks. The frequency of severe anaemia (packed-cell volume < 25%) and malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys.\n The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron (0.62 vs 0.87 cases per person-year; protective efficacy 28.8% [95% CI 6.3-45.8). Iron supplementation had no effect on the frequency of malaria (0.87 vs 1.00 cases per person-year; protective efficacy 12.8% [-12.8 to 32.5]). The groups that received malaria prophylaxis had lower frequencies of both severe anaemia (0.45 vs 1.04 episodes per person-year; protective efficacy 57.3% [43.0-67.9]) and malaria (0.53 vs 1.34 episodes per person-year; protective efficacy 60.5% [48.2-69.9]) than the groups that did not receive prophylaxis. After the end of the intervention period, children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups (relative risks 2.2 [1.3-3.7] and 1.8 [1.3-2.6]).\n Malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity. Iron supplementation was effective in preventing severe anaemia without increasing susceptibility to malaria. Our findings support iron supplementation of infants to prevent iron-deficiency anaemia, even in malaria-endemic areas." ]

[ "15034503", "21700360", "17451383", "3549810", "1935254", "8129407", "3549809", "8225725", "1428436", "17324826", "12072067", "17168873", "2250110", "17986309", "1607678", "7901248", "12524069", "19416259" ]

[ "A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss.", "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.", "Comparison of the efficacy and safety of topical minoxidil and topical alfatradiol in the treatment of androgenetic alopecia in women.", "Topical minoxidil (3%) in extensive alopecia areata, including long-term efficacy.", "Topical minoxidil in the treatment of androgenetic alopecia in women.", "Androgenetic alopecia in the female. Treatment with 2% topical minoxidil solution.", "Double-blind, placebo-controlled evaluation of topical minoxidil in extensive alopecia areata.", "Use of topical minoxidil therapy for androgenetic alopecia in women.", "Treatment of female androgenetic alopecia with minoxidil 2%.", "A randomized, placebo-controlled trial of 1% topical minoxidil solution in the treatment of androgenetic alopecia in Japanese women.", "Effects of minoxidil 2% vs. cyproterone acetate treatment on female androgenetic alopecia: a controlled, 12-month randomized trial.", "A pilot study evaluating the efficacy of topically applied niacin derivatives for treatment of female pattern alopecia.", "Quantitative estimation of hair growth. I. androgenetic alopecia in women: effect of minoxidil.", "Topical fulvestrant solution has no effect on male and postmenopausal female androgenetic alopecia: results from two randomized, proof-of-concept studies.", "Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration.", "Treatment of chronic severe alopecia areata with topical diphenylcyclopropenone and 5% minoxidil: a clinical and immunopathologic evaluation.", "Treatment of hyperandrogenic alopecia in women.", "Efficacy and safety of calcipotriol plus betamethasone dipropionate scalp formulation compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized controlled trial." ]

[ "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.", "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.", "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.", "This study was conducted to further evaluate the safety and efficacy of 3% topical minoxidil in the treatment of extensive alopecia areata. Patients were assigned to one of two treatment regimens in a double-blind manner. One group applied 3% minoxidil to the scalp twice daily for 64 weeks; the other group applied placebo for the initial 12 weeks and then switched to 3% minoxidil for the remaining 52 weeks. Thirty male and female subjects, ages 7 to 63 years, with extensive alopecia areata affecting 25% to 100% of the scalp were enrolled, fifteen subjects to each treatment group. Twenty-four of the thirty subjects had greater than 75% scalp hair loss. At 12 weeks the group treated with 3% minoxidil had slightly more hair growth than the placebo group, but the difference was not statistically significant. At 64 weeks, thirteen of twenty subjects (65%) who began with less than full scalp involvement (25% to 99% scalp hair loss) had terminal hair growth that was incomplete or cosmetically acceptable; of these, nine (45%) were cosmetically acceptable, a response that is significant in patients with severe alopecia areata. No hair growth or only slight growth was seen in all nine patients with 100% scalp hair loss at baseline. Thus the extent of hair loss at baseline was correlated with response at 64 weeks. Twenty-one of the patients continued treatment for a second year. Of these, thirteen showed further growth, three had no further growth, and five who had cosmetically acceptable hair growth during the first year had some hair loss.(ABSTRACT TRUNCATED AT 250 WORDS)", "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.", "The safety and efficacy of 3% topical minoxidil were evaluated in the treatment of extensive patchy alopecia areata, alopecia totalis, and alopecia universalis. Patients with extensive patchy alopecia areata had greater than 50% scalp hair loss. In this double-blind study, thirty subjects applied minoxidil or placebo to half of the afflicted scalp area twice daily, with overnight petrolatum occlusion, for 1 year. Both male and female subjects, ranging in age from 9 to 65 years, were enrolled, fifteen subjects to each treatment group. Minoxidil applications were generally well tolerated except for three instances of scalp itching and dermatitis, two of which necessitated discontinuing the medication. Hair growth was seen in seven of eleven evaluable subjects (63.6%) in the minoxidil group and in five of fourteen evaluable subjects (35.7%) in the placebo group. Excellent, cosmetically acceptable hair growth was seen in three of eleven minoxidil-treated subjects (27.3%) and in one of fourteen placebo-treated subjects (7.1%). Examination of vital signs and laboratory measurements revealed no evidence of systemic effects of minoxidil. Seven of the twelve subjects assayed in the minoxidil group had detectable minoxidil serum levels, ranging from 0.4 to 7.5 ng/ml.", "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.", "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%.", "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.", "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.", "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.", "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.", "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.", "The therapeutic value of topical minoxidil in alopecia areata (AA) has been investigated in recent years, with variable results. Although the mechanism whereby minoxidil may stimulate hair regrowth in some cases of AA has not yet been elucidated, there have been reports of a decrease in the perifollicular infiltrates of mononuclear leukocytes (MNC)--particularly T lymphocytes--that characterize this condition, in patients \"responding\" to topical minoxidil. In a randomized and double-blind study, we have investigated the effect of 5% topical minoxidil versus placebo (vehicle alone) on the extent and composition of the perifollicular MNC infiltration in 20 patients having extensive AA (26-99% scalp hair loss). The proportions of hair follicles showing perifollicular infiltration by MNC and their main subsets were determined with histologic and immunohistochemical stainings of scalp biopsies obtained before treatment, after 12 weeks of randomized double-blind minoxidil versus placebo treatment, and after 12 additional weeks during which all patients received minoxidil. Six of the patients showed cosmetically acceptable hair regrowth (CAHR) at the end of the 24 weeks and this was associated with a significant decrease in the proportions of follicles infiltrated by total T and B lymphocytes, macrophages, and Langerhans cells at week 12, and by total T lymphocytes at week 24. However, no significant differences in the extent or composition of the perifollicular infiltrates were detected at week 12 between patients receiving minoxidil and placebo, or between the week-12 and week-24 biopsies of those patients who first received placebo and then minoxidil. These findings indicate that in AA the reduction in perifollicular T-cell infiltration associated with CAHR is not attributable to an effect of topical minoxidil.", "Topical diphenylcyclopropenone (DPCP) and minoxidil have been used in the treatment of alopecia areata with variable results.\n This study was designed to evaluate the efficacy of DPCP alone or in combination with topical 5% minoxidil for the treatment of chronic severe alopecia areata. The effect of therapy on cutaneous T-cell and Langerhans cell subpopulations and intercellular adhesion molecule-1 (ICAM-1) expression was also examined.\n Fifteen patients with chronic (more than 2 years), severe (more than 50% scalp involvement) alopecia areata participated in a 24-week trial. Half of the scalp was treated with DPCP once weekly and with either 5% minoxidil solution or a vehicle solution twice daily in a randomized double-blind design. Skin biopsy specimens from each half of the scalp were obtained before therapy and after 12 and 24 weeks of therapy for histologic and immunophenotypic analysis.\n Thirteen patients completed the study. Five of 13 patients (38%) showed marked regrowth of coarse terminal hair after 24 weeks of treatment with DPCP. The addition of topical 5% minoxidil did not produce any significant clinical benefit in this 24-week trial. Immunophenotypic analysis showed no differences between responders and nonresponders at baseline. During treatment, Leu-4, Leu-2, Leu-3, and keratinocyte ICAM-1 expression were significantly reduced in biopsy specimens of responders versus nonresponders.\n DPCP treatment showed a 38% success rate in producing cosmetically acceptable regrowth in patients with chronic severe alopecia areata.", "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.", "Current topical therapies for scalp psoriasis are difficult or unpleasant to apply, resulting in decreased adherence and efficacy.\n To compare the efficacy and safety of once-daily treatment with a combination of calcipotriol 50 microg g(-1) plus betamethasone 0.5 mg g(-1) (as dipropionate) (Xamiol; LEO Pharma A/S, Ballerup, Denmark) and twice-daily calcipotriol 50 microg mL(-1) scalp solution in patients with scalp psoriasis.\n This 8-week, multicentre, randomized, investigator-blind, parallel-group study compared two-compound calcipotriol/betamethasone scalp formulation with calcipotriol scalp solution in patients with moderately severe scalp psoriasis. Primary efficacy outcome was the proportion of patients who achieved 'clear' or 'minimal' disease severity according to investigator's global assessment of disease severity at week 8. Secondary efficacy outcomes and adverse events were also evaluated. Relapse and rebound were assessed in an 8-week, post-treatment observation phase.\n In total, 207 patients received the two-compound scalp formulation and 105 patients received calcipotriol scalp solution. The proportion of patients with 'clear' or 'minimal' disease at week 8 was significantly greater in the two-compound scalp formulation group (68.6%) than in the calcipotriol scalp solution group (31.4%; P < 0.001). Improvement was more rapid with the two-compound scalp formulation than with calcipotriol scalp solution. Further evidence of the superiority of the two-compound scalp formulation over the scalp solution was demonstrated through greater improvements in clinical signs and fewer adverse events.\n A once-daily combination of calcipotriol plus betamethasone dipropionate was significantly more effective and better tolerated than twice-daily calcipotriol scalp solution in the treatment of scalp psoriasis." ]

[ "12009350", "16818032", "16984757", "9804219", "11006179", "9457941", "7989521", "12042269", "19568761", "7836534", "18765001", "9647536", "1555692", "8612863", "1740204" ]

[ "Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist.", "Delaying the initiation of progesterone supplementation until the day of fertilization does not compromise cycle outcome in patients receiving donated oocytes: a randomized study.", "Artificial versus stimulated cycles for endometrial preparation prior to frozen-thawed embryo transfer.", "Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study.", "Prospective randomized trial to evaluate the efficacy of a vaginal ring releasing progesterone for IVF and oocyte donation.", "Experience with a novel vaginal progesterone preparation in a donor oocyte program.", "Human menopausal gonadotrophin increases pregnancy rate in comparison with clomiphene citrate during replacement cycles of frozen/thawed pronucleate ova.", "A prospective randomized study: day 2 versus day 5 embryo transfer.", "Local injury to the endometrium on the day of oocyte retrieval has a negative impact on implantation in assisted reproductive cycles: a randomized controlled trial.", "The use of gonadotrophin-releasing hormone analogues in women receiving oocyte donation does not affect implantation rates.", "Progesterone supplementation during cryopreserved embryo transfer cycles: efficacy and convenience of two vaginal formulations.", "The use of long- and short-acting forms of gonadotrophin-releasing hormone analogues in women undergoing oocyte donation.", "The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization.", "Comparison of intravenous albumin and transfer of fresh embryos with cryopreservation of all embryos for subsequent transfer in prevention of ovarian hyperstimulation syndrome.", "The impact of long-term gonadotropin-releasing hormone analogue treatment on preclinical abortions in patients with severe endometriosis undergoing in vitro fertilization-embryo transfer." ]

[ "To 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.", "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.", "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.", "Transfer of frozen-thawed embryos is usually carried out in a natural cycle or in a programmed cycle in which the endometrium is exogenously stimulated following down-regulation of the hypophysis. To analyse the possibility that the programmed cycle for embryo transfer can still be hormonally manipulated without the use of gonadotrophin-releasing hormone agonist (GnRHa) we have conducted a prospective randomized study that compared the outcome of frozen-thawed embryo transfer cycles using micronized 17beta-oestradiol and micronized progesterone preparations with and without the concomitant use of GnRHa. One hundred and six patients were randomly divided into two groups. In group A (53 patients) 4 mg/day of micronized 17beta-oestradiol was initiated following down-regulation of hypophysis. In group B (53 patients) oestrogen stimulation started on day 1 of the cycle without prior pituitary down-regulation using a dose of 6 mg/day for 7 days. In both groups, micronized progesterone in a dose of 900 mg/day was administered vaginally after at least 12 days of oestrogen stimulation. Embryo transfer embryo transfer took place 48-72 h thereafter according to the cryopreserved embryonic stage. Overall, none of the patients had any follicular development and only one cycle in group B had to be cancelled because of premature progesterone secretion. The two groups did not differ in age (31+/-5.6 and 31+/-5.0 years), number of embryos transferred per patient (3.4+/-1.2 and 3.3+/-1.0), and day of progesterone initiation (15+/-2.2 and 15+/-1.9 for groups A and B respectively). The endometrial thickness on the day of progesterone initiation was comparable in both groups (11 +/-1.6 and 10+/-1.6 mm for groups A and B respectively). Similarly, the pregnancy rate per embryo transfer and implantation rate in group A (26.4% and 9.5%) were comparable to those of group B (21.1% and 9%). These results indicate that programmed cycles can be successfully applied by administering a high dose of micronized 17beta-oestradiol starting on day 1 of the cycle. Compared to GnRHa programmed cycles, this approach is simpler, more convenient for both the patient and medical staff, and results in a similar success rate at a lower cost.", "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 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.", "In a prospective randomized study, the effect of two ovulation induction regimens on implantation rate of frozen/thawed pronucleate ova was investigated. Patients received either human menopausal gonadotrophin (HMG) or clomiphene/HMG. Ovulation induction was done on an individual basis using ultrasound and plasma 17 beta-oestradiol concentrations. Ovulation was induced with human chorionic gonadotrophin (HCG) when the leading follicle reached a diameter of 18 mm. Pronucleate ova had been frozen using the slow-freezing method of Lassalle et al. (1985) (Fertil. Steril., 44, 645-651) and were thawed in synchrony with the age of the endometrium. Both groups of patients were comparable for age, indication for in-vitro fertilization, pre-ovulatory 17 beta-oestradiol concentration, number of large follicles and number and quality of embryos transferred. The only difference found was that HCG was administered 1 day earlier in the HMG group compared to the clomiphene/HMG group (P < 0.01). Using univariate analysis, the pregnancy rate was higher in patients stimulated with HMG alone compared to those stimulated with clomiphene/HMG (27 versus 15% respectively; P < 0.03), when HCG was administered later in the menstrual cycle (P < 0.01) and when more and better quality embryos were transferred (P < 0.01). Using multivariate regression analysis, the influence of the stimulation on pregnancy rate was even more pronounced (P < 0.01) when the day of HCG administration and the number and quality embryos transferred were taken into account. Therefore, we conclude that HMG alone increases pregnancy rate compared to clomiphene/HMG during replacement cycles of frozen/thawed pronucleate ova. These data suggest that HMG results in a better endometrium receptivity for embryos.(ABSTRACT TRUNCATED AT 250 WORDS)", "This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers.\n Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred.\n The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%).\n This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers.", "To evaluate the effect of local injury to the endometrium on the day of oocyte retrieval on implantation and pregnancy rates in assisted reproductive cycles.\n In a prospective controlled trial, a total of 156 patients, <38 years old, in their first in vitro fertilization (IVF) cycle were randomized. In 77 patients, two small endometrial samples from anterior and posterior walls of uterus were obtained with a Novak curette on the day of oocyte retrieval and in 79 patients no intervention was performed.\n The experimental and control patients were matched regarding women's age, body mass index, basal FSH, duration and etiology of infertility, treatment protocol, number of retrieved oocyte, endometrial thickness, percentage of intracytoplasmic sperm injection performance, fertilization rate, the percentage of patients with good and top quality embryos, and the number of embryos transferred. The implantation rate (7.9 vs. 22.9%), clinical (12.3 vs. 32.9%; odds ratio = 0.25; 95% confidence interval = 0.12-0.66; p < 0.05) and ongoing pregnancy (9.6 vs. 29.1%; odds ratio = 0.25; 95% confidence interval = 0.10-0.64; p < 0.05) rates were significantly lower in experimental group, compared with 79 controls.\n According to the results of this study, local injury to the endometrium on the day of oocyte retrieval disrupts the receptive endometrium and has a negative impact on implantation and IVF outcomes.", "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.", "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.", "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.", "To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle.\n Prospective randomized study.\n Ninety-one patients having their first attempt at IVF.\n Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle.\n The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2.\n The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF.", "To compare the efficacy of administration i.v. albumin to prevent severe ovarian hyperstimulation syndrome (OHSS) in patients undergoing ovarian stimulation for IVF with a standard policy of cryopreserving all embryos and to assess the impact of the two methods of treatment on pregnancy rates (PRs).\n Prospective randomized study.\n A tertiary referral center for assisted conception.\n Twenty-six patients undergoing IVF treatment cycles who were considered to be at high risk of developing severe OHSS on the basis of their serum E2 concentrations on the day of hCG administration and the number of oocytes collected.\n In group 1 (n = 13) all the generated embryos were cryopreserved to be transferred subsequently in hormonally manipulated cycles. In group 2 (n = 13) patients received IV infusions of albumin on the day of oocyte retrieval and 5 days later. Patients in group 2 had transfers of fresh embryos.\n The total dosage of hMG used, total number of follicles developed, number of follicles > 14 mm in diameter, serum E2 concentrations and endometrial thickness on day of hCG administration, number of oocytes retrieved, number and quality of embryos generated, PRs per cycle commenced, and onset and degree of any OHSS developed.\n There were no significant differences in the above parameters between the two groups, except for PRs that were significantly higher in patients who had all embryos cryopreserved (38.6% versus 0%).\n The policy of cryopreserving all generated embryos appears as effective as the administration of i.v. albumin in preventing OHSS in high-risk patients and produces significantly higher PRs.", "To examine the relationship between endometriosis and preclinical abortions and to evaluate the effect of gonadotropin-releasing hormone analogue (GnRH-a) therapy on these pregnancies.\n Of 67 women with severe endometriosis referred to us for in vitro fertilization-embryo transfer (IVF-ET), 32 underwent ovarian stimulation for oocyte retrieval with menotropins (protocol A), whereas the other 35 were admitted for the procedure after a 6-month period of hormonal suppression with a GnRH agonist (protocol B). The clinical impact of the preclinical and clinical pregnancies in both treatment protocols were evaluated on the basis of oocyte classification and embryo quality score.\n All patients were treated in our IVF Unit.\n Clinical pregnancy was used as our main outcome measure of success.\n A significantly higher number of preclinical pregnancies (P less than 0.0001) occurred in patients treated by protocol A. After GnRH-a treatment, the preclinical pregnancy rate declined significantly (P less than 0.0001), whereas the clinical pregnancy rate per cycle and per transfer rose significantly (P less than 0.0001 and P less than 0.0001, respectively). Furthermore, clinical pregnancies had a significantly better mean embryo quality score in comparison with preclinical pregnancies (P less than 0.0001).\n It is concluded that combining GnRH-a therapy before IVF-ET provides an improved treatment modality for preclinical abortions and infertility associated with severe endometriosis." ]

[ "20216531", "15944167" ]

[ "Cognitive-behavioral therapy for children with functional abdominal pain and their parents decreases pain and other symptoms.", "A randomized controlled trial of a cognitive-behavioral family intervention for pediatric recurrent abdominal pain." ]

[ "Unexplained abdominal pain in children has been shown to be related to parental responses to symptoms. This randomized controlled trial tested the efficacy of an intervention designed to improve outcomes in idiopathic childhood abdominal pain by altering parental responses to pain and children's ways of coping and thinking about their symptoms.\n Two hundred children with persistent functional abdominal pain and their parents were randomly assigned to one of two conditions-a three-session intervention of cognitive-behavioral treatment targeting parents' responses to their children's pain complaints and children's coping responses, or a three-session educational intervention that controlled for time and attention. Parents and children were assessed at pretreatment, and 1 week, 3 months, and 6 months post-treatment. Outcome measures were child and parent reports of child pain levels, function, and adjustment. Process measures included parental protective responses to children's symptom reports and child coping methods.\n Children in the cognitive-behavioral condition showed greater baseline to follow-up decreases in pain and gastrointestinal symptom severity (as reported by parents) than children in the comparison condition (time x treatment interaction, P<0.01). Also, parents in the cognitive-behavioral condition reported greater decreases in solicitous responses to their child's symptoms compared with parents in the comparison condition (time x treatment interaction, P<0.0001).\n An intervention aimed at reducing protective parental responses and increasing child coping skills is effective in reducing children's pain and symptom levels compared with an educational control condition.", "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", "791584", "3475231" ]

[ "Randomized trial of administration of prostaglandin E2 gel for induction of labor in the morning or the evening.", "Double-blind trial of prostaglandin F2alpha and oxytocin in the induction of labour.", "[Comparison between prostaglandin E2 gel and oxytocin in medically indicated labor induction]." ]

[ "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.", "In a random double-blind trial in 28 pregnant women at term, labour was induced with either prostaglandin F2alpha or oxytocin given by intravenous infusion. The results showed that prostaglandin F2alpha was as active as oxytocin and induction was successfully carried out in 24 patients; 3 patients had a caesarean section because of an obstructed labour and 1 patient on oxytocin did not have regular contractions after 10-hours' infusion although she delivered spontaneously 2 days later. No difference was found in the induction--delivery interval in the 8 patients in each group who had early amniotomy (first 90 minutes). No adverse effects were noted in either mother or the child. The authors recommend that to avoid side-effects the dosage of 20 mug prostaglandin F2alpha per minute should not be exceeded and that, although no cardiotocographic abnormalities were noted, this method of control should be used.", "The use of prostaglandins (PG) increasingly replaces the \"classical\" method of induction of labour by means of oxytocin and amniotomy, the last-named method being associated, especially in women with an unripe cervix, with side effects like prolonged labour and a higher rate of obstetric surgery. In this study the point of interest was whether prostaglandins offer any advantages over the classical method in respect of efficacy and maternal and foetal tolerance. 99 patients subdivided into primiparae and multiparae were randomly assigned to group A or B. In group A labour was induced with 1 mg resp. 2 mg PGE2 intravaginally at an interval of 6 hours. In group B the method of induction consisted of intravenous oxytocin and amniotomy. The success rate of induction was almost equal in both groups. However, in those patients where PGE2 induction did not succeed and who could not be delivered within 12 hours the cervical score was significantly improved in comparison to the oxytocin group. Based on the experience reported in the literature, one might speculate that an increased dosage could still improve the results of vaginally administered PGE2 gel." ]

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

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

[ "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.", "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.", "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.", "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." ]

[ "9250846", "11511121", "12783106", "12971850" ]

[ "A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group.", "A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study.", "Enoxaparin monotherapy without oral anticoagulation to treat acute symptomatic pulmonary embolism.", "[Early intravenous thrombolysis with recombinant tissue plasminogen activator for acute cerebral infarction]." ]

[ "Antithrombotic therapy with heparin plus aspirin reduces the rate of ischemic events in patients with unstable coronary artery disease. Low-molecular-weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, and does not require monitoring.\n In a double-blind, placebo-controlled study, we randomly assigned 3171 patients with angina at rest or non-Q-wave myocardial infarction to receive either 1 mg of enoxaparin (low-molecular-weight heparin) per kilogram of body weight, administered subcutaneously twice daily, or continuous intravenous unfractionated heparin. Therapy was continued for a minimum of 48 hours to a maximum of 8 days, and we collected data on important coronary end points over a period of 30 days.\n At 14 days the risk of death, myocardial infarction, or recurrent angina was significantly lower in the patients assigned to enoxaparin than in those assigned to unfractionated heparin (16.6 percent vs. 19.8 percent, P=0.019). At 30 days, the risk of this composite end point remained significantly lower in the enoxaparin group (19.8 percent vs. 23.3 percent, P=0.016). The need for revascularization procedures at 30 days was also significantly less frequent in the patients assigned to enoxaparin (27.1 percent vs. 32.2 percent, P=0.001). The 30-day incidence of major bleeding complications was 6.5 percent in the enoxaparin group and 7.0 percent in the unfractionated-heparin group, but the incidence of bleeding overall was significantly higher in the enoxaparin group (18.4 percent vs. 14.2 percent, P=0.001), primarily because of ecchymoses at injection sites.\n Antithrombotic therapy with enoxaparin plus aspirin was more effective than unfractionated heparin plus aspirin in reducing the incidence of ischemic events in patients with unstable angina or non-Q-wave myocardial infarction in the early phase. This benefit of enoxaparin was achieved with an increase in minor but not in major bleeding.", "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.", "Conventional anticoagulation for symptomatic pulmonary embolism consists of continuous intravenous unfractionated heparin as a \"bridge\" to oral anticoagulation. This strategy requires 5 days or more of intravenous heparin while oral vitamin K antagonists gradually achieve a therapeutic effect. Oral vitamin K antagonists require frequent blood testing to optimize dosing, and their interactions with other medications and foods make regulation difficult. Therefore we tested a different approach to therapy: long-term enoxaparin monotherapy. We randomized 60 symptomatic pulmonary embolism patients in a 2:1 ratio to 90 days of enoxaparin as monotherapy without warfarin (N=40) or to intravenous unfractionated heparin as a \"bridge\" to warfarin, target INR 2.0-3.0 (N=20). Enoxaparin patients received 1 mg/kg twice daily for 14 days during the acute phase followed by randomized assignment during the chronic phase to 1.0 mg/kg vs. 1.5 mg/kg once daily. In an intention-to-treat analysis, 3 of the 40 enoxaparin patients developed recurrent venous thromboembolism compared with 0 of 20 standard therapy patients (p = 0.54). One of the 40 enoxaparin patients had a major hemorrhagic complication compared with 2 of the 20 standard therapy patients (p = 0.26). Median hospital length of stay was shorter with enoxaparin compared to standard therapy (4 vs. 6 days) (p = 0.001). Following our study we can conclude that extended 3-month treatment with enoxaparin as monotherapy for symptomatic, acute pulmonary embolism is feasible and warrants further study in a large clinical trial.", "To evaluate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) and to explore the most suitable dosage of rt-PA in the early treatment of the Chinese patients with acute cerebral infarction (ACI).\n The patients who suited for the standard were divided into three groups. Group A received rt-PA at 0.9 mg/kg, group B received rt-PA at 0.7 mg/kg, and group C did not receive any thrombolytic therapy. In thrombolytic groups, rt-PA at 8 mg was injected intravenously in a bolus at first and then the rest was given over 60 minutes. The maximal dosage was 90 mg. The Chinese stroke scale (CSS) and Barthel Index (BI) were used to evaluate the recovery of neurological functions after rt-PA treatment for 24 hours and 90 days. The hemorrhagic rate and 30 days mortality rate were also analysed.\n In group A the CSS significant effective rate was 41.18 percent at 24 hours and 76.47 percent at 90 days after thrombolysis. At 90 days BI significant effective rate was 58.82 percent. At 30 days hemorrhagic rate was 8.82 percent and mortality rate was 5.88 percent. In group B, the CSS significant effective rate was 39.39 percent at 24 hours and 69.70 percent at 90 days. At 90 days, BI significant effective rate was 54.55 percent, and at 30 days, hemorrhagic rate was 9.09 percent and mortality rate was 9.09 percent. In group C, the CSS significant effective rate was 21.21 percent, at 24 hours and 30.30 percent at 90 days (P>0.05). At 90 days, BI was 21.21 percent the mortality rate was 9.09 percent. At 30 days the mortality rate was no significant difference within three groups At 90 days, significant effective rate was 73.13 percent vs. 30.30 percent in thrombolytic and control groups (P=0.001 7). The significant disability rate was 13.43 percent vs. 24.24 percent.\n For Chinese individuals, with ACI, rt-PA thrombolysis was effective and safe. The dosage of 0.9 mg/kg for foreign people also fitted for Chinese individuals." ]

[ "11851660", "9864116", "20428997", "19816918", "11704169", "12847356", "9231856", "11744900", "15570204", "21979458", "8103365" ]

[ "Randomized clinical trial of laparoscopic versus open abdominal rectopexy for rectal prolapse.", "Comparison of laparoscopic rectopexy with open technique in the treatment of complete rectal prolapse: clinical and functional results.", "Anterior vaginal wall prolapse: a randomized controlled trial of SIS graft versus traditional colporrhaphy.", "Physiotherapy as an adjunct to prolapse surgery: an assessor-blinded randomized controlled trial.", "Laparoscopic Burch colposuspension: a randomized controlled trial comparing two transperitoneal surgical techniques.", "Prospective, randomized, controlled trial between a pathway of controlled rehabilitation with early ambulation and diet and traditional postoperative care after laparotomy and intestinal resection.", "Comparison of polyglycolic acid and polypropylene mesh for rectopexy in the treatment of rectal prolapse.", "Anterior colporrhaphy: a randomized trial of three surgical techniques.", "Hand-assisted laparoscopic versus open restorative proctocolectomy with ileal pouch anal anastomosis: a randomized trial.", "Laparoscopic compared with robotic sacrocolpopexy for vaginal prolapse: a randomized controlled trial.", "Clinical and functional results of abdominal rectopexy with absorbable mesh-graft for treatment of complete rectal prolapse." ]

[ "The objectives of this study were to compare both subjective clinical outcomes and the objective stress response of laparoscopic and open abdominal rectopexy in patients with full-thickness rectal prolapse. Abdominal rectopexy for patients with rectal prolapse is well suited for a laparoscopic approach as no resection or anastomosis is necessary.\n Forty patients with a full-thickness rectal prolapse were randomized before operation to a laparoscopic group and an open group. They agreed to conform to a clinical pathway (CP) of liquid diet (CP1) and full mobility (CP2) on day 1, solid diet (CP3) on day 2 and discharge (CP4) before day 5. Their compliance was monitored by an assessor blinded to the operative group, who also rated pain and mobility. Patient-controlled morphine use was documented. Neuroendocrine and immune stress response and respiratory function were measured.\n Some 75 per cent of all clinical pathway objectives of early recovery were achieved in the laparoscopic group compared with 37 per cent in the open group (P < 0.01). Significant differences in favour of laparoscopy were noted with regard to narcotic requirements, and pain and mobility scores. Differences in objective measures of stress response favouring laparoscopy were found for urinary catecholamines, interleukin 6, serum cortisol and C-reactive protein. No differences were noted in respiratory function but significant respiratory morbidity was greater in the open group (P < 0.05). None of the measured outcomes, subjective or objective, favoured the open group apart from operating time, which was significantly shorter (153 versus 102 min; P < 0.01).\n This study has demonstrated significant subjective and objective differences in favour of a laparoscopic technique for abdominal rectopexy. The advantages were all short term but no evidence of any adverse effect on longer-term outcomes was observed.", "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.", "This study seeks to compare the small intestine submucosa (SIS) graft with traditional colporrhaphy (TC) for surgical treatment of anterior vaginal prolapse.\n Subjects were randomly assigned to SIS (n = 29) or to TC (n = 27) preoperatively and outcomes analyzed at 12 months postoperatively. The primary outcome was the absence of POP-Q stage >or= II prolapse, and secondary outcome was improvement in quality of life. Data were compared with independent samples or paired Student's t test.\n SIS group had 86.2% anatomic cure compared to 59.3% in TC (p = 0.03). SIS improved point Ba measurement significantly (-1.93 cm versus -1.37 cm, p = 0.02). Both operations significantly improved quality of life, although there were no differences between the groups. We observed a greater number of complications in the SIS group, with no infections or erosion.\n SIS repair improved point Ba significantly. However, there were no differences observed in quality of life between the techniques.", "This assessor-blinded randomized controlled trial investigated the effect of a pre- and post-operative physiotherapy-supervised pelvic floor muscle (PFM) training program in women undergoing surgery for prolapse or hysterectomy.\n Participants were assessed pre-operatively, and at 3, 6, and 12 months post-operatively by a blinded physiotherapy assessor. Following randomization, participants were allocated to a control group (CG) which included \"usual care\" (as provided by the surgeon and the hospital staff), or a treatment group (TG) which included one pre-operative and seven post-operative treatment sessions over 12 months. Primary outcomes were bladder and prolapse symptoms, measured by the Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ).\n Fifty-one participants were randomized. The 12-month post-operative findings showed there was no difference in the prevalence of the primary outcomes (ORs 1.2, 1.3). There were no significant differences between groups on the change scores of the UDI (mean: 44.1 [5.1]; 54.0 [5.4], P = 0.20) nor the IIQ (median: 0.0 [9,14]; 10.0 [5,19], P = 0.09). The repeated measures analyses also demonstrated no significant changes.\n The program tested did not improve bladder or prolapse symptoms in this trial. Reasons may include the effectiveness of surgery alone, wide variance in data, small sample size, insufficient training by the TG, and PFM training by the usual care group.\n (c) 2010 Wiley-Liss, Inc.", "To compare the effectiveness of two transperitoneal laparoscopic Burch procedures.\n The sample size required was 30 subjects per group to detect a statistically significant estimated difference of 15% between two surgical procedures with an alpha = 0.05 and a power of 0.7. Sixty women affected by genuine stress incontinence (GSI) were enrolled and randomly assigned to two groups of 30 women each. All women were treated with the transperitoneal laparoscopic Burch procedure using nonabsorbable sutures (group A) or Prolene mesh (Ethicon, Somerville, NJ) fixed with tacks or staples (group B). The failure rate was defined subjectively and objectively. The subjective evaluation was performed by asking the women to rate their urine loss on a visual analog scale. The objective evaluation was a clinical evaluation using multichannel urodynamic studies.\n The subjective failure rate was not significantly different between the two groups at 3 months (0% for both groups), 6 months (3.7% versus 3.8% for groups A and B, respectively), and 12 months (7.4% versus 15.4% for groups A and B, respectively) after surgery. At 3 months (3.7% versus 3.8% for groups A and B, respectively) and 6 months (7.4% versus 15.4% for groups A and B, respectively) follow-up, the objective failure rate was not significantly different between the two groups. However, at 12 months after the surgical procedure, the objective failure rate was significantly lower in group A than in group B (11.1% versus 26.9%, respectively; P <.05).\n Transperitoneal laparoscopic Burch colposuspension performed using sutures was more effective than the mesh technique.", "In an era of dwindling hospital resources and increasing medical costs, safe reduction in postoperative stay has become a major focus to optimize utilization of healthcare resources. Although several protocols have been reported to reduce postoperative stay, no Level I evidence exists for their use in routine clinical practice.\n Sixty-four patients undergoing laparotomy and intestinal or rectal resection were randomly assigned to a pathway of controlled rehabilitation with early ambulation and diet or to traditional postoperative care. Time to discharge from hospital, complication and readmission rates, pain level, quality of life, and patient satisfaction scores were determined at the time of discharge and at 10 and 30 days after surgery. Subgroups were defined to evaluate those who derived the optimal benefit from the protocol.\n Pathway patients spent less total time in the hospital after surgery (5.4 vs. 7.1 days; P = 0.02) and less time in the hospital during the primary admission than traditional patients. Patients younger than 70 years old had greater benefits than the overall study group (5 vs. 7.1 days; P = 0.01). Patients treated by surgeons with the most experience with the pathway spent significantly less time in the hospital than did those whose surgeons were less experienced with the pathway (P = 0.01). There was no difference between pathway and traditional patients for readmission or complication rates, pain score, quality of life after surgery, or overall satisfaction with the hospital stay.\n Patients scheduled for a laparotomy and major intestinal or rectal resection are suitable for management by a pathway of controlled rehabilitation with early ambulation and diet. Pathway patients have a shorter hospital stay, with no adverse effect on patient satisfaction, pain scores, or complication rates. Patients younger than 70 years of age derive the optimal benefit, and increased surgeon experience improves outcome.", "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.", "The purpose of this study was to compare outcomes after anterior colporrhaphy with the use of 3 different surgical techniques.\n One hundred fourteen women with anterior vaginal prolapse were randomly assigned to undergo anterior repair by one of 3 techniques: standard, standard plus polyglactin 910 mesh, or ultralateral anterior colporrhaphy. Before and after operation, patients underwent physical examination staging of prolapse; the International Continence Society system was used. Symptoms were assessed by questionnaire and visual analog scales. We defined \"cure\" as satisfactory (stage I) or optimal (stage 0) outcome at points Aa and Ba.\n Of 114 patients who were originally enrolled, 109 patients underwent operation, and 83 patients (76%) returned for follow-up. Mean age (+/- SD) was 64.7 +/- 11.1 years. At entry, 7 patients (7%) had stage I anterior vaginal prolapse; 35 patients (37%) had stage II anterior vaginal prolapse; 51 patients (54%) had stage III anterior vaginal prolapse; and 2 patients (2%) had stage IV anterior vaginal prolapse. At a median length of follow-up of 23.3 months, 10 of 33 patients (30%) who were randomly assigned to the standard anterior colporrhaphy group experienced satisfactory or optimal anatomic results, compared with 11 of 26 patients (42%) with standard plus mesh and with 11 of 24 patients (46%) with ultralateral anterior colporrhaphy. The severity of symptoms that were related to prolapse improved markedly (preoperative score, 6.9 +/- 2.7; postoperative score, 1.1 +/- 0.8). Twenty-three of 24 patients (96%) no longer required manual pressure to void after operation.\n These 3 techniques of anterior colporrhaphy provided similar anatomic cure rates and symptom resolution for anterior vaginal prolapse repair. The addition of polyglactin 910 mesh did not improve the cure rate compared with standard anterior colporrhaphy.", "The aim of the study was to evaluate postoperative recovery after hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis in a randomized controlled trial.\n Sixty patients were randomized for hand-assisted laparoscopic (n = 30) or open surgery (n = 30). Primary outcome parameter was postoperative recovery in the 3 months after surgery, measured by quality of life questionnaires (SF-36 and GIQLI). Secondary parameters were postoperative morphine requirement and surgical parameters, viz. operating time, morbidity, hospital stay, and costs.\n There was no difference between the 2 procedures in quality of life assessment in the 3 months after surgery. There was a significant decline in quality of life on all scales of the SF-36 (P < 0.001) and total GIQLI score (P < 0.001) in the first 2 weeks in both groups (no significant difference between the groups). Quality of life returned to baseline levels after 4 weeks. Operating times were longer in the laparoscopic group compared with the open group (210 and 133 minutes, respectively; P < 0.001). No significant differences were found in morphine requirement. Neither morbidity nor postoperative hospital stay differed between the laparoscopic and open group (20% versus 17%, in 10 versus 11 days, respectively). Median overall costs were 16.728 for the hand-assisted laparoscopic procedure and 13.406 for the open procedure (P = 0.095).\n Recovery measured using quality of life questionnaires is comparable for hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis. The laparoscopic approach is as safe, but more costly than the open procedure.", "To compare conventional laparoscopic and robotic-assisted laparoscopic sacrocolpopexy for vaginal apex prolapse.\n This single-center, blinded randomized trial included participants with stage 2-4 posthysterectomy vaginal prolapse. Participants were randomized to laparoscopic or robotic sacrocolpopexy. The primary outcome was total operative time from incision to closure. Secondary outcomes were postoperative pain, functional activity, bowel and bladder symptoms, quality of life, anatomic vaginal support, and cost from a health care system perspective.\n A total of 78 patients enrolled and were randomized (laparoscopic n=38; robotic n=40). Total operative time was significantly longer in the robotic group compared with the laparoscopic group (+67-minute difference; 95% confidence interval [CI] 43-89; P<.001). Anesthesia time, total time in the operating room, total sacrocolpopexy time, and total suturing time were all significantly longer in the robotic group. Participants in the robotic group also had significantly higher pain at rest and with activity during weeks 3 through 5 after surgery and required longer use of nonsteroidal anti-inflammatory drugs (median, 20 compared with 11 days, P<.005). The robotic group incurred greater cost than the laparoscopic group (mean difference +$1,936; 95% CI $417-$3,454; P=.008). Both groups demonstrated significant improvement in vaginal support and functional outcomes 1 year after surgery with no differences between groups.\n Robotic-assisted sacrocolpopexy results in longer operating time and increased pain and cost compared with the conventional laparoscopic approach.", "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." ]

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[ "Sequential protocols using basiliximab versus antithymocyte globulins in renal-transplant patients receiving mycophenolate mofetil and steroids.", "Two-dose basiliximab compared with two-dose daclizumab in renal transplantation: a clinical study.", "Basiliximab versus antithymocyte globulin for prevention of acute renal allograft rejection.", "Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal graft recipients.", "Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group.", "Immunoprophylaxis with basiliximab compared with antithymocyte globulin in renal transplant patients receiving MMF-containing triple therapy.", "Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. II. Results after a second kidney transplantation.", "Reduction of acute renal allograft rejection by daclizumab. Daclizumab Double Therapy Study Group.", "Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group.", "A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients.", "A single-dose daclizumab induction protocol in renal allograft recipients: a Chinese single center experience.", "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.", "Rabbit antithymocyte globulin versus basiliximab in renal transplantation.", "Daclizumab versus antithymocyte globulin in high-immunological-risk renal transplant recipients.", "CMV infections after two doses of daclizumab versus thymoglobulin in renal transplant patients receiving mycophenolate mofetil, steroids and delayed cyclosporine A.", "Basiliximab reduces the incidence of acute cellular rejection in live-related-donor kidney transplantation: a three-year prospective randomized trial.", "Basiliximab (Simulect) reduces acute rejection among sensitized kidney allograft recipients.", "Limited dose monoclonal IL-2R antibody induction protocol after primary kidney transplantation.", "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-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial.", "Single bolus antithymocyte globulin versus basiliximab induction in kidney transplantation with cyclosporine triple immunosuppression: efficacy and safety.", "Steroid-withdrawal at 3 days after renal transplantation with anti-IL-2 receptor alpha therapy: a prospective, randomized, multicenter study.", "A double-blind, placebo-controlled study of monoclonal anti-interleukin-2 receptor antibody (BT563) administration to prevent acute rejection after kidney transplantation.", "A randomized trial of steroid avoidance in renal transplant patients treated with everolimus and cyclosporine.", "Efficacy and safety of basiliximab in pediatric renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.", "Tacrolimus-Basiliximab versus Cyclosporine-Basiliximab in renal transplantation \"de novo\": acute rejection and complications.", "Multicenter randomized prospective trial of steroid withdrawal in renal transplant recipients receiving basiliximab, cyclosporine microemulsion and mycophenolate mofetil.", "A randomized prospective study comparing low-dose OKT3 to low-dose ATG for the treatment of acute steroid-resistant rejection episodes in kidney transplant recipients.", "Aggressive treatment of the first acute rejection episode using first-line anti-lymphocytic preparation reduces further acute rejection episodes after human kidney transplantation.", "Therapy of acute cadaveric renal allograft rejection with adjunctive antithymocyte globulin.", "Viral prophylaxis in combined pancreas-kidney transplant recipients.", "Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO).", "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.", "A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation.", "[Cytokines and growth factors serum level and renal allograft function (preliminary report)].", "Valacyclovir for cytomegalovirus prophylaxis reduces the risk of acute renal allograft rejection.", "Randomized comparison of ganciclovir plus intravenous immune globulin (IVIG) with IVIG alone for prevention of primary cytomegalovirus disease in children receiving liver transplants.", "A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation.", "Calcineurin inhibitor avoidance with daclizumab, mycophenolate mofetil, and prednisolone in DR-matched de novo kidney transplant recipients.", "Failure of high-dose oral acyclovir with or without immune globulin to prevent primary cytomegalovirus disease in recipients of solid organ transplants.", "Cytomegalovirus antigenemia directed pre-emptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial.", "A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients.", "Multicenter, randomized study of the effectiveness of basiliximab in avoiding addition of steroids to cyclosporine a monotherapy in renal transplant recipients.", "Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation.", "Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group.", "Individualized T cell monitored administration of ATG versus OKT3 in steroid-resistant kidney graft rejection.", "Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group [corrected].", "High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. A 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.", "A comparison of ganciclovir and acyclovir to prevent cytomegalovirus after lung transplantation.", "Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database." ]

[ "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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 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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "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.", "Steroids have been included in most immunosuppressive regimens after renal transplantation, but are feared for their side-effects. We conducted a prospective multicenter study to investigate whether it is feasible to withdraw steroids early after transplantation with the use of anti-IL-2Ralpha induction, tacrolimus and mycophenolate mofetil (MMF). A total of 364 patients were randomized to receive either two doses of daclizumab (1 mg/kg) and, for the first 3 days, 100 mg of prednisolone (daclizumab group n = 186), or steroids (tapered to 0 mg at week 16; controls n = 178). All patients received tacrolimus and MMF. The incidence of biopsy-confirmed acute rejection at 12 months was not different between the daclizumab group (15%) and the controls (14%) (95% confidence interval of difference: -6 to + 8%, NS). Graft survival at 12 months was comparable in the two groups (daclizumab group: 91%; controls: 90%). Mean arterial blood pressure, serum lipids, and incidence of patients with hyperglycemia were temporary lower in the daclizumab group compared with controls. The immunosuppressive regimen of the daclizumab group was associated with increased costs. In conclusion, with the use of anti-IL-2Ra induction and daily therapy with tacrolimus and MMF it is feasible to withdraw steroids at 3 days after renal transplantation.", "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.", "In this randomized trial renal transplant recipients were treated with basiliximab, everolimus 3 mg/day, low-dose CsA. At transplantation, patients were randomized to stop steroids at the seventh day (group A) or to continue oral steroids in low doses (group B). Of the 113 patients enrolled, 65 were randomized to group A and 68 to group B. All patients were followed for 2 years. During the study 28 (43%) group A patients required reintroduced corticosteroids. One patient died, in group B. The Graft survival rate was 97% in group A and 90% in group B. There were more biopsy-proven rejections in group A (32% vs 16%; P = .044). The mean creatinine clearance was 54 +/- 21 mL/min in group A vs 56 +/- 22 mL/min in group B. Mean levels of serum cholesterol tended to be lower in group A, but the difference was of borderline significance (191 +/- 91 vs 251 +/- 188 mg/dL; P = .07). Vascular thrombosis (0 vs 5) and pneumonia requiring hospitalization (2 vs 7) tended to be more frequent in group B. Only three cases of CMV infection (1 vs 2) occurred. An immunosuppressive therapy with everolimus and low-dose CsA allows one to obtain excellent renal graft survival and stable graft function at 2 years. Early interruption of steroids in patients treated with this regimen may increase the risk of acute rejection, but neither affects graft survival nor graft function, while possibly reducing the risk of hyperlipemia and vascular thrombosis. About 60% of patients given everolimus and low-dose CsA can definitively stop steroids after 1 week.", "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.", "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.", "Corticosteroids withdrawal from immunosuppressive regimens has thus far been associated with increased risk of acute rejection episodes. In this study, basiliximab, a chimeric monoclonal interleukin-2 receptor antagonist, added to a maintenance regimen consisting of cyclosporine microemulsion and mycophenolate mofetil was studied for its effectiveness in allowing early corticosteroid withdrawal in de novo renal allograft recipients. Primary renal transplant recipients receiving basiliximab, cyclosporine-microemulsion, and mycophenolate mofetil, were randomized to either corticosteroid withdrawal at day four post-transplantation (n = 40) or standard steroid therapy (n = 43). The primary endpoint was the incidence of biopsy-proven acute rejection episodes. Randomized subjects who underwent transplantation and received at least one dose of basiliximab were analyzed in an intent-to-treat fashion. The incidence of biopsy-proven acute rejection at 12 months was not significantly different between the steroid withdrawal group (20%) and the standard treatment group (16%). Patient and graft survival was 100% in the steroid withdrawal group while one death in a patient with a functioning graft occurred in the standard steroid group. Seventy-two percent of the steroid withdrawal group remained off steroids at 6 months post-transplant. Allograft function and incidence of adverse events and infections were similar between the two groups. Rapid and early corticosteroid withdrawal among renal transplant recipients receiving basiliximab induction and daily therapy with cyclosporine-microemulsion and mycophenolate mofetil was not associated with an increased risk of acute rejection.", "Acute steroid-resistant rejection episodes in kidney allograft recipients require treatment with antilymphocyte antibodies. Monoclonal anti-CD3 and polyclonal antilymphocyte antibodies have been widely used but seldom compared. Recent data have suggested that these antibodies could be used at reduced doses without jeopardizing their efficacy. In this study, we randomized renal transplant recipients who encountered a first acute steroid-resistant rejection episode to low-dose ATG or low-dose OKT3 treatment. Sixty patients were enrolled in the study. They received prophylactic immunosuppression with cyclosporin, azathioprine, and prednisolone. Treatment of biopsy-proven rejection consisted of a 10-day course of either ATG (n = 31) or OKT3 (n = 29). The total ATG dose was 484 +/- 110 mg, i.e., 0.75 mg/kg per day. The total OKT3 dose was 32 +/- 4 mg, i.e., 0.05 mg/kg per day. We compared reversion of rejection, side effects, immunodepression, and graft function. Reversion of rejection was similar in the two groups, although we noted a trend in favor of ATG. Results were 3% vs 10% early graft failures, 13% vs 23% overall graft failures, 28% vs 38% 3-month actuarial incidence of rebound rejection, and 89% vs 81% 1-year graft survival rate in the ATG and OKT3 groups, respectively. Tolerance was worse in the OKT3 group due to the first-dose syndrome. Infections and cancers occurred with the same frequency. ATG resulted in a deeper and longer decrease in peripheral lymphocyte subsets. Graft function was similar in the two groups. We conclude that low-dose ATG and low-dose OKT3 are equally effective in reversing steroid-resistant acute rejection. Tolerance was better with ATG, which also gave a more potent and longlasting immunodepression. The use of reduced doses of ATG and OKT3 did not appear to lessen their efficacy.", "The detrimental effect of acute rejection episodes on long-term outcome of renal allografts in cyclosporin-treated patients is well established, although has not been seen by all investigators. To analyse the possibility that aggressive treatment of the first episode may ameliorate this detrimental effect, we performed an open label, randomised prospective trial in cyclosporin-based, immunosuppressed recipients of postmortem renal allografts in order to compare two different treatment protocols during primary acute rejection episodes: (1) group 1 of 25 patients received 3 x 250 mg methylprednisolone (MP) i.v.; (2) group 2 of 25 patients received 7 x anti-thymocyte globulin (ATG)-Fresenius i.v. (4 mg/kg body weight). During a period of 4 years, the following clinical observations were made: (1) The incidence of an acute re-rejection episode was significantly reduced in the ATG-treated study group (16%) compared to the MP-treated study group (72%); (2) The severity of the first acute rejection episode (intensity of renal dysfunction measured in terms of 10-day creatinine area under curve) showed no significant difference between the groups (37 mg x 10-d/dl to 58 mg x 10-d/dl); and (3) The half-lives of allografts in both groups have not shown any significant differences so far. In conclusion, aggressive treatment of the first rejection episode of renal allografts with the use of ATG reduced the incidence of re-rejection episodes which, however, are not reflected so far by improvement of the 4-year survival rate of these allografts. Since it could be observed that re-rejection is an even worse predictor for chronic transplant failure, a better long-term outcome of renal allografts in ATG-treated patients may be expected during a longer observation period. The incidence of a third episode was also reduced in the ATG-treated group (0%) compared to the MP-treated group (12%).", "A randomized and controlled study was conducted to evaluate the efficacy of adjunctive antithymocyte globulin (ATG) therapy for the treatment of the initial rejection episode in first cadaveric transplants. When compared to the control group (29), which received only standard antirejection treatment (SAT) of steroid pulsing and local irradiation, the adjunctive ATG treatment group (23) demonstrated significantly faster recovery rates (8.9 +/- 4.1 versus 6.9 +/- 3.7 days, P = 0.05, respectively) and better graft survival rates (62 +/- 9% versus 91 +/- 7%, respectively) after the first rejection. ATG treatment did not result in fewer subsequent rejection episodes than SAT but long-term allograft survival rates remained superior to controls for the entire 3-year study period. By avoiding ATG treatment in those patients who never experienced clinical rejection on maintenance immunosuppressive therapy, i.e., nonresponders (23 of 90), complications associated with excessive immunosuppression were minimized. The combined results of the non-responder group of patients and ATG-treated patients resulted in a 1-year patient survival of 97% and graft survival of 86%. These results suggest that the most efficacious use of ATG is therapeutic and not prophylactic in renal transplant patients.", "The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immunosuppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (IVIG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclovir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard IVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100-150 mg/kg) plus 2 weeks of i.v. ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommended that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure.", "One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29); (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P =.8) in the first and in 50% versus 11% (P =.001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P =.02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%; P =.04), as confirmed by multivariate analysis (P =.03). Time to 50 x 10(9)/L platelets was comparable in the first trial (21 vs 24 days; P =.3) and delayed in the ATG arm in the second trial (23 vs 38 days; P =.02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.", "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.", "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.", "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.", "Both oral ganciclovir and valacyclovir decrease the incidence of cytomegalovirus (CMV) disease after renal transplantation. Moreover, valacyclovir has been shown to reduce the risk of acute rejection. Our study was designed to compare the efficacy and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease after renal transplantation.\n A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir (8 g/day, n=35, VAL). A control group (DEF, n=12) was managed by deferred therapy.\n No differences were found in demography, immunosuppression, or donor/recipient CMV serology. The 12-month incidence of CMV disease was 67% in the DEF group compared with 6% in the GAN group and 3% in the VAL group (P<0.001 GAN or VAL vs. DEF; P=0.575 GAN vs. VAL). The biopsy-confirmed acute rejection rate at 12 months was 12% in the VAL group compared with 34% in the GAN group (P=0.030) and 58% in the DEF group (P<0.001). The difference between the GAN and DEF groups was not significant (P=0.087). The average CMV-associated costs per patient were $3,072, $2,906, and $4,906 in the GAN, VAL, and DEF groups, respectively.\n Valacyclovir and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation. Both regimens are cost-effective. Valacyclovir is associated with a significantly reduced risk of acute rejection compared with both ganciclovir prophylaxis and deferred therapy.", "A randomized placebo-controlled trial was conducted to determine the benefit of ganciclovir (5 mg/[kg x d]) for 30 days in addition to intravenous immune globulin (IVIG) for 16 weeks for prevention of primary cytomegalovirus (CMV) disease in children receiving liver transplants. Patients were monitored for 6 months after transplantation. The two groups of patients (recipients of 29 ganciclovir plus IVIG and 27 recipients of IVIG alone) were similar in terms of age, sex, and underlying disease. The incidence of CMV disease among the ganciclovir plus IVIG recipients and the IVIG alone recipients was 17% and 26%, respectively, and the time to disease in these recipients was 46 days and 32 days, respectively. There was no difference between groups in terms of survival; episodes of rejection, bacteremia, or fungemia; use of immunosuppressive agents; and incidence of leukopenia or thrombocytopenia. These results suggest that a 4-week course of ganciclovir with IVIG is not more effective than IVIG alone for prevention of primary CMV disease. Since short-term prophylaxis with ganciclovir may delay the onset of CMV disease, further studies with a longer course of ganciclovir prophylaxis are warranted.", "Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n = 133; GCV+HIg, n = 133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n = 28, 21.0%) in the ACV group, while significantly more patients (n = 42, 31.6%) in the GCV + HIg group developed group developed CMV disease slightly later (2.83 +/- 0.70 months) than those who received GCV/HIg (2.15 +/- 0.21 months, P > 0.01). Multivariate analysis demonstrated (2.15 +/- 0.21 months, P > 0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P < 0.001), while the difference between ACV versus GCV + HIg prophylaxis was also significant (P = 0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV + HIg prophylaxis is used in this patient population.", "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.", "To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants.\n We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease.\n All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%).\n Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population.", "The efficacy of pre-emptively administered oral ganciclovir in preventing cytomegalovirus (CMV) disease has not been documented in liver transplant recipients. We sought to compare the efficacy of pre-emptive oral ganciclovir with that of i.v. ganciclovir for the prevention of CMV disease after liver transplantation, and to determine whether withholding prophylaxis in the absence of CMV antigenemia, reliably identified patients in whom no prophylaxis was necessary.\n Surveillance cultures for CMV pp65 antigenemia were performed in all patients at weeks 2, 4, 6, 8, 12, and 16. Patients with CMV antigenemia were randomized into two study groups. The experimental group received oral ganciclovir for 6 weeks (2 g t.i.d. for 2 weeks, then 1 g t.i.d. for 4 weeks), and the control group received i.v. ganciclovir (5 mg/kg q 12 hr) for 7 days.\n Of 72 consecutive liver transplant recipients studied, CMV antigenemia occurred in 31% (22 of 72). Twenty-two patients with asymptomatic antigenemia were randomized to two study groups. CMV disease (viral syndrome) occurred in 9% (1 of 11) of the patients in the i.v. ganciclovir group and in 0% (0 of 11) of the patients in the oral ganciclovir group. None of the study patients developed tissue invasive CMV disease. The median reduction in antigenemia level with oral ganciclovir was 55% at week 1, and 100% at week 2. Overall, 64% of the patients by week 1, 93% by week 2, and 100% by week 4 had antigenemia levels below the baseline after oral ganciclovir. Of 50 patients without CMV antigenemia, none developed CMV disease.\n Pre-emptive prophylaxis based on CMV antigenemia can effectively target the patients for CMV prophylaxis; 69% of the patients never received antiviral prophylaxis and did not develop CMV disease. Antiviral therapy instituted upon detection of antigenemia prevented tissue invasive CMV in both ganciclovir groups. Pre-emptively administered oral ganciclovir was effective as prophylaxis for CMV disease after liver transplantation.", "Posttransplantation cytomegalovirus (CMV) infection remains a significant cause of morbidity in kidney transplant recipients. We performed a randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for CMV prophylaxis in a group of renal allograft recipients considered at high risk for CMV disease due to the use of OKT3 induction therapy.\n A total of 101 recipients of cadaveric (83) and zero haplotype-matched live donor (18) kidney transplants were entered into the trial. A total of 22 D-R- patients received no prophylaxis. Twenty-seven D+R-, 29 D+R+, and 23 D-R+ patients were randomized to receive 3 months of either oral acyclovir (800 mg q.i.d.) or oral ganciclovir (1000 mg t.i.d.). Doses were adjusted according to the level of renal function. The D+R- patients were also given CMV immune globulin biweekly for 16 weeks. Surveillance blood cultures were obtained at transplantation, at months 1, 2, 3, and 6, and when clinically indicated. The primary study end points were time to CMV infection and disease the first 6 months after transplantation.\n The mean follow up was 14.4 months. Both agents were well tolerated, and no drug interruptions for toxicity occurred. CMV was isolated in 14 of 39 (35.9%) acyclovir-treated and 1 of 40 (2.5%) ganciclovir-treated recipients by 6 months (P=0.0001). Symptomatic CMV disease occurred in 9 of 14 (64%) of the acyclovir patients, two with tissue-invasive disease. Infection rates for acyclovir vs. ganciclovir, respectively, stratified by CMV serology were: D+R-, 54 vs. 0%, P=0.0008; D+R+, 43 vs. 6.6%, P=0.01; D-R+, 8.3 vs. 0%, P=NS. No patient developed CMV infection while taking oral ganciclovir, however three delayed infections occurred 2-7 months after finishing therapy. Each patient had been previously treated for acute rejection.\n Oral acyclovir provides effective CMV prophylaxis only for recipients of seronegative donor kidneys. Oral ganciclovir is a superior agent providing effective CMV prophylaxis for recipients of seropositive donor kidneys. Recipients who are treated for acute rejection are at risk for delayed CMV infection during the first posttransplantation year.", "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.", "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.", "The novel agent sirolimus (SRL; Rapamune; rapamycin) inhibits the immune response by a mechanism distinct from those of calcineurin antagonists or antimetabolites. This randomized, controlled, multicenter, single blind, phase II trial examined the combination of SRL, steroids, and full versus reduced doses of cyclosporine (CsA) for prophylaxis of acute renal allograft rejection.\n A total of 149 recipients of mismatched cadaveric- or living-donor primary renal allografts were randomized into six groups. Three groups received placebo or 1 or 3 mg/m2/day SRL, as well as steroids and full-dose CsA (Sandimmune). Three groups received steroids, reduced-dose CsA (target trough level 50% of full-dose range), and 1, 3, or 5 mg/m2/day SRL.\n The incidence of biopsy-proven acute rejection episodes within the first 6 months after transplant was reduced from 32.0% in the control group to 8.5% in patients receiving SRL (1 or 3 mg/m2/day) and full-dose Sandimmune CsA (P=0.018). Similar low rates of acute rejection episodes were observed among non-African-Americans, but not African-Americans, treated with SRL and reduced-dose Sandimmune CsA. Despite the augmented immunosuppression, 1-year patient and graft survival rates did not differ significantly across groups. Adverse effects attributable to CsA, including hypertension and new-onset diabetes mellitus, were not exacerbated by SRL. Except for an increased incidence of pneumonia among patients receiving full-dose CsA and 3 mg/m2/day SRL, the incidences of opportunistic infections were similar in all treatment groups. Although SRL produced more frequent, but reversible, hematological and lipid abnormalities, it had no apparent nephrotoxic effects to exacerbate CsA-induced renal dysfunction.\n SRL in combination with CsA and steroids not only lowers the incidence of biopsy-proven acute renal allograft rejection episodes, but also may permit CsA sparing, at least among Caucasian patients, without an increased risk of rejection.", "Acute steroid-resistant rejection episodes are recommended to be treated with set doses of anti-thymocyte globulin (ATG) or anti-CD3 monoclonal antibody (OKT3). Individualized T cell monitoring has been proposed as a tool for dose finding. A randomized study comparing the efficacy and safety of ATG (n = 27) with OKT3 (n = 28) in the treatment of biopsy verified acute steroid-resistant rejection (ASRR) when both drugs were administered on the basis of daily individualized T cell measurements. A drop to below 50 cells/mm3 CD2+ T cells was considered adequate and used to guide the dose of ATG/OKT3. Demographic, clinical and histopathological severities of rejections were equal in the two groups. During the 10 days of T cell monitoring and antibody treatment, 13 patients were in need of dialysis (ATG = 7/OKT3 = 6). Two grafts did not respond to antibody treatment and were lost due to rejection (ATG = 1/OKT3 = 1). There were 26 biopsy verified re-rejections (ATG = 12/OKT3 = 14) within the first 3 months following antibody treatment. Mean serum creatinine (micromol/L) was similar in the two groups (ATG/OKT3: before rejection 157 +/- 72/151 +/- 88, at start of antibody treatment 308 +/- 125/330 +/- 94, end of antibody treatment 254 +/- 122/246 +/- 144 and at follow-up after a mean of 32 months 166 +/- 55 (n = 24)/164 +/- 57(n = 23)). To keep the T cell count below 50 cells/mm3, average dose ATG given was 354 +/- 151 mg (2.3 administrations, range 1-4) and average OKT3 was 32.5 +/- 6.8 mg in 10 doses. In conclusion, individualized T cell monitored administration of ATG and OKT3 is safe and seems as effective as a standard set dose in treatment of ASRR. Tailoring the dose for each individual patient lowers the cost.", "Cytomegalovirus (CMV) disease is a frequent cause of serious morbidity after solid-organ transplantation. The prophylactic regimens used to prevent CMV infection and disease have shown limited benefit in seronegative recipients. We studied the safety and efficacy of oral ganciclovir in the prevention of CMV disease following orthotopic liver transplantation.\n Between December, 1993, and April, 1995, 304 liver-transplant recipients were randomised to receive oral ganciclovir 1000 mg or matching placebo three times a day. Seronegative recipients of seronegative livers were excluded. Study drug was administered as soon as the patient was able to take medication by mouth (no later than day 10) until the 98th day after transplantation. Patients were assessed at specified times throughout the first 6 months after surgery for evidence of CMV infection, CMV disease, rejection, opportunistic infections, and possible drug toxicity.\n The Kaplan-Meier estimate of the 6-month incidence of CMV disease was 29 (18.9%) of 154 in the placebo group, compared with seven (4.8%) of 150 in the ganciclovir group (p < 0.001). In the high-risk group of seronegative recipients (R-) of seropositive livers (D+), incidence of CMV disease was 11 (44.0%) of 25 in the placebo group, three (14.8%) of 21 in the ganciclovir group (p = 0.02). Significant benefit was also observed in those receiving antibodies to lymphocytes, where the incidence of CMV disease was 12 (32.9%) of 37 in the placebo group and two (4.6%) of 44 in the ganciclovir group (p = 0.002). Oral ganciclovir reduced the incidence of CMV infection (placebo 79 [51.5%] of 154; ganciclovir 37 [24.5%] of 150; p < 0.001) and also reduced symptomatic herpes-simplex infections (Kaplan-Meier estimates: placebo 36 [23.5%] of 154; ganciclovir five [3.5%] of 150; p < 0.001).\n Oral ganciclovir is a safe and effective method for the prevention of CMV disease after orthotopic liver transplantation.", "To assess the efficacy of high-dose oral acyclovir therapy compared with preemptive, short-course ganciclovir therapy (administered only if cytomegalovirus [CMV] shedding occurred) to prevent CMV disease in liver transplant recipients.\n A randomized controlled trial.\n Liver transplant center at a university-affiliated Veterans Affairs Medical Center.\n 47 consecutive patients having liver transplantation.\n Patients were stratified by their CMV antibody status and the CMV antibody status of the donor and were randomly assigned to one of two treatment groups. Surveillance cultures for CMV (buffy coat and urine) were done every 2 to 4 weeks for 24 weeks in all patients. One group received high-dose oral acyclovir (800 mg four times daily). The experimental group received no acyclovir, but if surveillance cultures were positive, ganciclovir (5 mg/kg intravenously twice daily) was administered for 7 days.\n Cytomegalovirus shedding and CMV disease were measured in the two groups.\n Cytomegalovirus shedding before the onset of CMV disease occurred in 25% (6 of 24) of patients in the acyclovir group compared with 22% (5 of 23) in the experimental group. Cytomegalovirus disease developed in 29% (7 of 24) of the acyclovir group and in 4% (1 of 23) of the experimental group (P < 0.05). No hematologic toxicity occurred with ganciclovir.\n Oral acyclovir is ineffective prophylaxis against CMV in liver transplant recipients. Preemptive, short-course ganciclovir therapy in patients with CMV shedding was well tolerated and provided effective prophylaxis against subsequent CMV disease; this protocol targets the patients at risk for CMV disease and minimizes toxicity and expense.", "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.", "In an attempt to modify the sequelae of cytomegalovirus (CMV) infections after lung transplantation, 25 allograft recipients were randomized to either ganciclovir 5 mg/kg once a day 5 d/wk (Group G) or acyclovir 800 mg four times a day (Group A). All subjects received ganciclovir during postoperative Weeks 1 through 3, and they were then given either A or G regimens until Day 90. At termination of study enrollment, the cumulative incidence of all CMV infections (including seroconversions) was increased in Group A compared with that in Group G (75% versus 15%, p < 0.01), as was the incidence of overt CMV shedding and/or pneumonitis (50% versus 15%, p < 0.043). In comparison with those in Group G, subjects in Group A were also afflicted with an increased prevalence of obliterative bronchiolitis (OB) during the first year after transplantation (54% versus 17%, p < 0.033). Intravenous catheters for ganciclovir administration resulted in four complications among three of the subjects in Group G (23%). The short-term benefits of ganciclovir were ultimately limited, moreover, in that cumulative rates of CMV and prevalence of OB are now similar in both treatment groups after approximately 2 yr of observation. We conclude that prolonged ganciclovir prophylaxis decreases the early incidence of CMV and OB among lung transplant recipients, but these effects are of finite duration. Although CMV prevention appears to have considerable potential value in this population, definitive viral prophylaxis will require development of protracted or repeated treatment regimens, or longer-acting agents.", "The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone.\n One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages.\n During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05).\n Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group." ]

[ "17461960", "8558397", "15642026", "9857596", "11966923", "15877748", "15536784", "9545899", "15101598", "16996783", "11516001" ]

[ "Peri-implant maintenance of immediate function implants: a pilot study comparing hyaluronic acid and chlorhexidine.", "The effect of an antiseptic mouthrinse on implant maintenance: plaque and peri-implant gingival tissues.", "Therapy of peri-implantitis with resective surgery. A 3-year clinical trial on rough screw-shaped oral implants. Part I: clinical outcome.", "Clinical and microbiologic effects of chemical versus mechanical cleansing in professional supportive implant therapy.", "Relative effectiveness of powered and manual toothbrushes in elderly patients with implant-supported mandibular overdentures.", "Treatment of peri-implantitis by the Vector system.", "Treatment of incipient peri-implant infections using topical minocycline microspheres versus topical chlorhexidine gel as an adjunct to mechanical debridement.", "Effects of subgingival chlorhexidine irrigation on peri-implant maintenance.", "Cemented versus screw-retained implant-supported single-tooth crowns: a 4-year prospective clinical study.", "Rehabilitation of oral function in head and neck cancer patients after radiotherapy with implant-retained dentures: effects of hyperbaric oxygen therapy.", "Implant-retained mandibular overdentures with Brånemark System MKII implants: a prospective comparative study between delayed and immediate loading." ]

[ "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 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.", "The purpose of this randomized clinical trial was to compare the clinical outcome of two different surgical approaches for the treatment of peri-implantitis. Seventeen patients with ITI(R) implants were included consecutively over a period of 5 years. The patients were randomized with a lottery assignment. Ten patients were treated with resective surgery and modification of surface topography (test group). The remaining seven patients were treated with resective surgery only (control group). Clinical parameters (suppuration, modified plaque index - mPI, modified bleeding index - mBI, probing pocket depth - PPD, pseudopocket - DIM, mucosal recession - REC, probing attachment level - PAL) were recorded at baseline, as well as 6, 12, 24 and 36 months after treatment. The cumulative survival rate for the implants of the test group was 100% after 3 years. After 24 months, two hollow-screw implants of control group were removed because of mobility. Consequently, the cumulative survival rate was 87.5%. The recession index in the control group was significantly lower than in the test group at 24 months (Student's t-value of -2.14). On the contrary, control group showed higher PPD, PAL and mBI indexes than test group (Student's t-values of +5.5, +2.4 and +9.61, respectively). The PPD and mBI indexes for the implants of the control group were significantly higher at baseline than 24 months later (Student's t-values of +3.18 and +3.33, respectively). Recession and PAL indexes resulted in values significantly lower than baseline (Student's t-values of -4.62 and -2.77, respectively). For the implants of the test group PPD and mBI indexes were significantly higher at baseline than 36 months after (Student's t-values of +11.63 and +16.02, respectively). Recession index resulted in values significantly lower at baseline (Student's t-value of -5.05). No statistically significant differences were found between PAL index measurement at baseline and 36 months later (Student's t-value of +0.89). In conclusion, resective therapy associated with implantoplasty seems to influence positively the survival of oral implants affected by inflammatory processes.", "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 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.", "To compare the effectiveness of treatment of peri-implantitis with a novel ultrasonic device, the Vector system, with that of subgingival debridement with carbon fiber curettes.\n The study, comprising 11 patients with at least two screw type implants with bleeding on probing (BOP), probing pocket depth (PPD) > or =5 mm, and at least 1.5 mm radiographic bone loss and exposed implant threads, was carried out as a single blind randomized clinical trial. At baseline one randomly chosen implant in each patient was treated by the Vector system (test) while the other implant (control) was treated by submucosal debridement with a carbon fiber curette. After 3 months, the same treatments were repeated. Plaque, BOP, and PPD were recorded on all implant surfaces at baseline, and after 3 and 6 months. Bone levels were recorded on radiographs taken prior to the start of the study, and after 6 months.\n Oral hygiene around both test and control implants was improved at 3 and 6 months compared with baseline. At 6 months, four of the Vector-treated sites, and only one site treated with curettes, had stopped to bleed. In neither the test nor the control group, were there any differences between baseline and 6 months regarding PPD and bone levels.\n Although there was a greater reduction in the number of sites with BOP following treatment with the Vector system than following instrumentation with carbon fiber curettes, there was no significant difference between the two methods.", "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.", "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.", "The purpose of this controlled prospective clinical study was to compare cemented and screw-retained implant-supported single-tooth crowns followed for 4 years following prosthetic rehabilitation with respect to peri-implant marginal bone levels, peri-implant soft tissue parameters, and prosthetic complications.\n Twelve consecutive patients were selected from a patient population attending the Implantology Department at the University of Padova. They all presented with single-tooth bilateral edentulous sites in the canine/premolar/molar region with adequate bone width, similar bone height at the implant sites, and an occlusal scheme that allowed for the establishment of identical occlusal cusp/fossa contacts. Each patient received 2 identical implants (1 in each edentulous site). One was randomly selected to be restored with a cemented implant-supported single-tooth crown, and the other was restored with a screw-retained implant-supported single-tooth crown. Data on peri-implant marginal bone levels and on soft tissue parameters were collected 4 years after implant placement and analyzed to determine whether there was a significant difference with respect to the method of retention (cemented versus screw-retained).\n All patients completed the study. All 24 implants survived, resulting in a cumulative implant success rate of 100%. Statistical analysis revealed no significant differences between the 2 groups with respect to peri-implant marginal bone levels and soft tissue parameters.\n The data obtained with this study suggested that the choice of cementation versus screw retention for single-tooth implant restorations is likely not based on clinical results but seems to be based primarily on the clinician's preference.\n Within the limitations of this study, the results indicate that there was no evidence of different behavior of the peri-implant marginal bone and of the peri-implant soft tissue when cemented or screw-retained single-tooth implant restorations were provided for this patient population.", "Surgical treatment of malignancies in the oral cavity and subsequent radiotherapy often result in an anatomic and physiological oral condition unfavorable for prosthodontic rehabilitation. The objective of this prospective study was to assess the effect of hyperbaric oxygen therapy on treatment outcome (condition of peri-implant tissues, implant survival, oral functioning and quality of life) of prosthodontic rehabilitation with implant-retained lower dentures in radiated head and neck cancer patients 6 weeks and 1 year after placing the new dentures. The treatment outcome was assessed in a group of 26 head neck cancer patients who were subjected to radiotherapy after tumour surgery. Standardized questionnaires were completed and clinical and radiographic assessments were performed. After randomization, endosseous Brånemark implants were placed in the anterior part of the mandible either under antibiotic prophylaxis (13 patients) or under antibiotic prophylaxis combined with pre and postsurgery hyperbaric oxygen (HBO) treatment (13 patients). In the HBO and non-HBO group eight implants (implant survival 85.2%) and three implants (implant survival 93.9%) were lost, respectively. Peri-implant tissues had a healthy appearance in both groups. Osteoradionecrosis developed in one patient in the HBO group. All patients functioned well with their implant-retained lower denture. The quality of life related to oral functioning and denture satisfaction were improved to a comparable extent in the HBO and non-HBO group. Implant-retained lower dentures can improve the quality of life related to oral functioning and denture satisfaction in head and neck cancer patients. Adjuvant hyperbaric oxygen therapy could not be shown to enhance implant survival in radiated mandibular jaw bone.", "This study was designed to compare the results of immediate and delayed loading of implants with implant-retained mandibular overdentures. Ten patients (test group) received 40 Brånemark System MKII implants (4 per patient) placed in the interforaminal area of the mandible. Standard abutments were immediately screwed to the implants, rigidly connected with a bar, and immediately loaded with an overdenture. Ten patients (control group) received the same type and number of implants in the same area, but the implants were left to heal submerged. Four to 8 months later, standard abutments were screwed to the implants and the same prosthetic procedure was applied. Each implant was evaluated at the time of prosthetic loading and at 6, 12, and 24 months after the initial prosthetic load with the following parameters: modified Plaque Index (MPI), modified Bleeding Index (MBI), probing depth (PD), and Periotest. Peri-implant bone resorption was evaluated on panoramic radiographs taken 12 and 24 months after initial prosthetic loading. No significant differences were found between the 2 groups regarding MPI, MBI, Periotest, peri-implant bone resorption, and PD at 6 and 24 months (P > .05). The only difference was found regarding PD values on the mesial and lingual sites at 12 months (P < .05). The cumulative success rate of implants was 97.5% in both groups. Results from this study showed that immediate loading of endosseous implants rigidly connected with a U-shaped bar does not seem to have any detrimental effect on osseointegration. Conversely, this method significantly shortens the duration of treatment with relevant satisfaction for the patients." ]

[ "8445463", "11302304", "11841372", "15160576", "8894860", "3063436", "8886085" ]

[ "Use of sodium hyaluronate in treating temporomandibular joint disorders: a randomized, double-blind, placebo-controlled clinical trial.", "Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group.", "Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel.", "An evaluation of Hyalofill-F plus compression bandaging in the treatment of chronic venous ulcers.", "Hyaluronidase (Hyalase): a useful addition in haematoma block?", "Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee.", "High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial." ]

[ "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.", "A prospective, multicenter, randomized, double-blind, controlled trial was conducted in 226 patients with knee osteoarthritis to evaluate the safety and efficacy of intraarticular injections of sodium hyaluronate. Patients were randomized to three weekly injections of 30 mg sodium hyaluronate or physiologic saline (control) and were observed for an additional 25 weeks. In comparison with the control group, among patients who completed at least 15 weeks of the study and whose Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was less than 12 at baseline, sodium hyaluronate injection resulted in improvement in Western Ontario and McMaster Universities Osteoarthritis Index pain score, patient and investigator global assessments, and pain on standing from Weeks 7 to 27. Fifty-eight percent of patients treated with sodium hyaluronate achieved a 5-unit or greater improvement in mean pain score from Weeks 7 through 27, compared with 40% of control patients. In addition, nearly twice as many patients treated with sodium hyaluronate as with saline (30% versus 17%, respectively) achieved a net improvement of at least 7 units. In contrast to treatment with saline, Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was inversely related to the magnitude of improvement after treatment with sodium hyaluronate. Few side effects were attributed to treatment, and no differences between treatment groups were seen in this respect (sodium hyaluronate, nine [8%]; saline, 11 [10%]). The incidence of injection site reactions was low (sodium hyaluronate, 1.2 %; saline, 1.5%). The results indicate that sodium hyaluronate treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee osteoarthritis in whom pain in the contralateral knee is relatively modest.", "Actinic keratoses (AKs) are premalignant skin lesions, which, if left untreated, can develop into squamous cell carcinoma. Current treatments for AKs are destructive and are often associated with significant adverse events. The development of an effective and well-tolerated topical treatment for AK is desirable.\n To evaluate the efficacy and safety of 3.0% diclofenac in 2.5% hyaluronan gel as a treatment for AK.\n This was a multicentre, double-blind, placebo-controlled study in which 195 patients with at least five AKs in up to three designated treatment blocks were randomized to four treatment groups. Patients randomized into the active treatment groups A30 (n = 49) and A60 (n = 48) received topical treatment with 3.0% diclofenac in 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Patients in the placebo (vehicle gel) groups V30 (n = 49) and V60 (n = 49) received topical treatment with 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Treatment efficacy was assessed by target and cumulative lesion number scores (TLNS and CLNS, respectively) and lesion total thickness score (TTS). Investigator and patient global improvement indices (IGII and PGII) were also used to rate overall improvement.\n Compared with placebo, significantly more patients given active treatment for 60 days had TLNS = 0 (33% vs. 10%, P < 0.05; an improvement of 64% compared with 34% with placebo), CLNS = 0 (31% vs. 8%, P < 0.05; an improvement of 54% compared with 23% with placebo) and TTS = 0 (25% vs. 6%, P < 0.05; an improvement of 59% compared with 31% with placebo). The IGII and PGII scores were also significantly better when active treatment was compared with placebo (P < 0.05). Both treatments were generally well tolerated and the incidence of the most common adverse events was similar between groups.\n Treatment with 3.0% diclofenac in 2.5% hyaluronan gel was effective when used for 60 days and was well tolerated in patients with AK.", "Hyaluronan, a component of the extracellular matrix, plays a significant role in several aspects of tissue repair and the wound healing process.\n In this Italian study Hyalofill-F, a partial benzyl ester derivative of hyaluronan, used in combination with compression bandaging, was compared with the well-established therapy in Italy of non-adherent gauze plus compression therapy in the treatment of chronic venous leg ulcers.\n Hyalofill-F plus compression bandaging performed significantly better than non-adherent gauze plus compression bandage in all of the clinically relevant efficacy parameters. Mean reduction in ulcer area in the hyaluronan-derivative group was 8.1 cm2 after eight weeks of treatment, compared with 0.4 cm2 in the comparator group. The resulting difference of 7.7 cm2 between the two groups was statistically significant (p = 0.0019). Furthermore, statistically significant results in favour of the hyaluronan-derivative group were obtained in the following: speed of epithelialisation; leveling of the margins; degree of maceration; pain intensity and frequency.\n Hyalofill-F plus compression bandaging resulted in an earlier and greater decrease in ulcer area compared with non-adherent gauze plus compression bandaging, therapy supporting its use in the treatment of chronic venous ulcers.", "To investigate whether hyaluronidase (Hyalase) is a useful and justified addition to haematoma block for pain relief.\n The study was a randomised double blind trial of 33 consecutive patients attending the accident and emergency department for manipulation of distal radius fracture under haematoma block. Control patients received 1% lignocaine; the treatment group received 1% lignocaine plus 1500 IU hyaluronidase. Manipulation occurred 10 minutes after instituting the block.\n 16 patients received hyaluronidase, 17 received lignocaine only. One patient with unsuccessful manipulation was excluded. There was no significant difference between the two groups for any of three methods of pain assessment (P > 0.05, Mann Whitney).\n The addition of hyaluronidase does not increase the efficacy of the haematoma block when 10 minutes are allowed to elapse before manipulation, and the increased cost of adding (and risk of allergy) is not justified by any theoretical increased speed of analgesia.", "A multi-centre randomized, double-blind, parallel-group clinical trial was carried out in 63 patients with osteoarthritis of the knee to compare the efficacy and tolerability of a course of intra-articular injections of 20 mg sodium hyaluronate with a similar course of injections of placebo. Treatment consisted of up to 11 injections over a 23-week period. Evaluation was by means of subjective symptom and activity assessments, serially during the course of treatment and also 25 weeks thereafter. Ten patients (5 of 30 on active treatment; 5 of 33 on placebo) were withdrawn prematurely. Pain on movement, assessed by visual analogue scale (VAS) showed statistically significant (p less than 0.05 to p less than 0.0001) reductions in mean scores throughout the first 11 weeks of treatment with sodium hyaluronate but smaller, non-significant, reductions with placebo treatment. The difference between treatments was significant (p less than 0.05) at 5 weeks. Pain at rest, also assessed by VAS, showed little change in mean scores with placebo but with sodium hyaluronate there was a progressive reduction which was significant (p less than 0.01) throughout the period from 5 to 23 weeks. The difference between sodium hyaluronate and placebo was significant (p less than 0.05 to p less than 0.002) at Weeks 5, 11, 15, 19 and 23. 'Activities of daily living' were assessed using a standard scale. There were small improvements with both treatments, significant at some assessments and somewhat greater with sodium hyaluronate than placebo, but there were no statistically significant differences between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "Hyaluronic acid is a natural component of cartilage and is considered not only as a lubricant in joints but also as playing a physiological role in the trophic status of cartilage. Hyalectin, a selected fraction of hyaluronic acid extracted from cocks' combs, has exhibited efficacy in animal models of osteoarthritis. To assess the efficacy and tolerability of intra-articular injections of hyalectin, we conducted a prospective, randomized, placebo-controlled trial of 1 years' duration in 110 patients with painful hydarthrodial osteoarthritis of the knee. At entry and once a week for 3 weeks, aspiration of the knee effusion and intra-articular injections of either hyalectin 20 mg (H) or its vehicle (C) were performed. The vehicle acted as the control treatment. Four weeks after the last injection, the improvement was greater in the H group compared with the C group (pain: -35.5 +/- 26.4 mm vs -25.8 +/- 21.4, P = 0.03, Lequesne's functional index: -3.8 +/- 4.3 vs -2.3 +/- 3.3, P = 0.03). During the 1 year follow-up, the need to perform supplementary local therapies (joint fluid aspiration because of painful hydarthrodial episodes and/or local corticosteroid injections) was more frequent in group C (44% vs 30%, P = 0.03). Moreover, at the final visit, the physician's overall assessment of efficacy was in favor of H (77% vs 54%, P = 0.01) and the improvement in the functional index was greater in group H (-4.4 +/- 5.1 vs -2.7 +/- 4.1, P = 0.05). This study suggests that intra-articular injections of hyalectin may (1) improve clinical condition and (2) have a long-term beneficial effect in patients with osteoarthritis of the knee." ]

[ "12745558", "16616557", "16641396" ]

[ "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.", "Vitamins C and E and the risks of preeclampsia and perinatal complications." ]

[ "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.", "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." ]

[ "9024451", "16877299", "11789240", "11006365" ]

[ "Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis.", "Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment.", "[Effect of Tripterygium polyglycoside on interleukin-6 in patients with Guillain-Barre syndrome].", "Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group." ]

[ "To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).\n Prospective, controlled, randomized study.\n Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.\n No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.\n Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly.", "D-Ala1-peptide T-amide (DAPTA) has shown neuroprotection in vitro against gp120-induced loss of dendritic arborization and is promulgated as a CCR5 antagonist. A multisite, randomized, double-blind clinical trial of DAPTA versus placebo prior to combination antiretroviral therapy conducted with human immunodeficiency virus (HIV)-1 seropositive participants having cognitive impairment showed no overall cognitive effect, though subgroups with greater impairment and CD4 cell counts of 201 to 500 cells/mm3 at baseline showed significant improvement. The objective of this study was to examine whether intranasal administration of DAPTA at a dose of 2 mg three times per day (tid) was associated with a reduction of cerebrospinal fluid (CSF) and peripheral (plasma and serum) viral load among a subgroup of participants completing 6 months of treatment. Baseline and 6-month CSF (n = 92) and peripheral (plasma n = 33; serum n = 24) viral load were measured by the Roche Ultrasensitive assay, version 1.5, with reflexive use of the AMPLICOR assay and preservation of the blind. A DAPTA treatment indicator variable was tested using generalized linear models on change in viral load. Peripheral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group. No group differences in CSF viral load were found. This retrospective study on a limited subgroup of the original trial sample indicated that DAPTA treatment may reduce peripheral viral load without concomitant CSF effects. Future studies should be undertaken to confirm the existence of this result and the CSF-periphery dissociation observed with respect to HIV-1-associated cognitive-motor impairment.", "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.", "Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value.\n We conducted a randomized, double-blind trial of 383 patients who had a first acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or brain-stem or cerebellar syndrome) and evidence of prior subclinical demyelination on magnetic resonance imaging (MRI) of the brain. After initial treatment with corticosteroids, 193 patients were randomly assigned to receive weekly intramuscular injections of 30 microg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo. The study end points were the development of clinically definite multiple sclerosis and changes in findings on MRI of the brain. The trial was stopped after a preplanned interim efficacy analysis.\n During three years of follow-up, the cumulative probability of the development of clinically definite multiple sclerosis was significantly lower in the interferon beta-1a group than in the placebo group (rate ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.002). As compared with the patients in the placebo group, patients in the interferon beta-1a group had a relative reduction in the volume of brain lesions (P<0.001), fewer new or enlarging lesions (P<0.001), and fewer gadolinium-enhancing lesions (P<0.001) at 18 months.\n Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinically definite multiple sclerosis." ]

[ "3317057", "19678813", "2193075", "16279903", "1863024", "19766640", "1885075", "15017515", "20049950", "19920971", "8677990", "17241860", "6381184", "19491859", "19375519", "20064514", "18080055", "20878425", "11709512", "8533995", "2202199", "2577483", "7914759", "17234558", "18832520", "15606398", "8580278", "8583101", "15017487", "7876505", "12094857", "18272546", "1980911", "11515850", "7502549", "19891665" ]

[ "Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.", "Clinical trial: ulcerative colitis maintenance treatment with 5-ASA: a 1-year, randomized multicentre study comparing MMX with Asacol.", "Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation. A double-blind placebo controlled trial.", "Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial.", "Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study.", "Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis.", "Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis.", "The optimal dose of 5-aminosalicylic acid in active ulcerative colitis: a dose-finding study with newly developed mesalamine.", "Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study.", "Once daily versus conventional dosing of pH-dependent mesalamine long-term to maintain quiescent ulcerative colitis: Preliminary results from a randomized trial.", "A comparison of mesalamine suspension enema and oral sulfasalazine for treatment of active distal ulcerative colitis in adults.", "Once-daily, high-concentration MMX mesalamine in active ulcerative colitis.", "A double-blind clinical trial to compare the effects of 4-aminosalicylic acid to 5-aminosalicylic acid in topical treatment of ulcerative colitis.", "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.", "Mesalamine once daily is more effective than twice daily in patients with quiescent ulcerative colitis.", "Once-daily dosing of delayed-release oral mesalamine (400-mg tablet) is as effective as twice-daily dosing for maintenance of remission of ulcerative colitis.", "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.", "Clinical trial: Effects of an oral preparation of mesalazine at 4 g/day on moderately active ulcerative colitis. A phase III parallel-dosing study.", "Low dose balsalazide (1.5 g twice daily) and mesalazine (0.5 g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0 g twice daily) was superior in preventing relapses.", "An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis. A randomized, placebo-controlled trial. The Mesalamine Study Group.", "5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial.", "Comparative efficacy of coated, oral 5-aminosalicylic acid (Claversal) and sulphasalazine for maintaining remission of ulcerative colitis. International Study Group.", "5-ASA enema versus oral sulphasalazine in maintaining remission in ulcerative colitis.", "Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of remission of mild to moderately active ulcerative colitis.", "Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial.", "Mesalazine (5-aminosalicylic acid) micropellets show similar efficacy and tolerability to mesalazine tablets in patients with ulcerative colitis--results from a randomized-controlled trial.", "Comparison of budesonide and 5-aminosalicylic acid enemas in active distal ulcerative colitis.", "Coated oral 5-aminosalicylic acid (Claversal) is equivalent to sulfasalazine for remission maintenance in ulcerative colitis. A double-blind study.", "A pilot feasibility study of once daily versus conventional dosing mesalamine for maintenance of ulcerative colitis.", "A randomized, double-blind, placebo-controlled trial of the oral mesalamine (5-ASA) preparation, Asacol, in the treatment of symptomatic Crohn's colitis and ileocolitis.", "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.", "Randomised trial of once- or twice-daily MMX mesalazine for maintenance of remission in ulcerative colitis.", "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.", "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.", "Comparison between high dose 5-aminosalicylic acid and 6-methylprednisolone in active Crohn's ileocolitis. A multicenter randomized double-blind study. German 5-ASA Study Group.", "Clinical trial: oral colon-release parnaparin sodium tablets (CB-01-05 MMX) for active left-sided 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.", "5-ASA-MMX (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis.\n To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study.\n In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for >or=1 month prior to the trial, with >or=1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months' treatment.\n In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated.\n Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis.", "Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (less than 20 cm) entered the trial. Thirty-two were treated with 5-ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p less than 0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis.", "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.", "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.", "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.", "5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p less than 0.001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis.", "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.", "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).", "Multiple studies have demonstrated the efficacy of aminosalicylates in maintaining remission in ulcerative colitis (UC). A newer formulation of mesalamine can be administered once daily. We aimed to examine the efficacy and tolerability of pH-dependent mesalamine for long-term maintenance, and compare the rates of medication consumption between groups over a prolonged period.\n Subjects whose UC had been quiescent for at least 4 months, and who had been receiving mesalamine for maintenance only, were randomized to once daily or conventional dosing for 12 months. Disease activity and medication consumption was assessed every 3 months. The primary endpoint was the percentage of those with quiescent disease at 12 months.\n We enrolled 20 patients, 12 to once daily and 8 to conventional dosing. Six of the 12 patients (50%) in the once daily group compared with 5 of the 8 patients (62.5%) in the conventional group experienced a flare (p = 0.31). Only 5 of the 12 (42%) patients in the once daily group were adherent compared with 3 of 8 patients (37.5%) in the conventional dosing group (p = NS). Median amount consumed in the once daily group was 63% (range 0%-100%) and in the conventional group 55% (range 0%-100%), (p > 0.5). None of the adherent subjects in the once daily group experienced a flare, while 6 out of 7 (86%) who were non-adherent experienced a flare (p < 0.01). In the conventional dosing group, 1 in 3 adherent patients (33%) experienced a flare compared with 4 out of 5 (80%) in the non-adherent group (p < 0.01).\n Adherence, rather than medication regimen, appeared to be important in disease outcome at 12 months.", "To compare the efficacy and safety of mesalamine (5-ASA) suspension enema versus oral sulfasalazine (SAS) in patients with active mild to moderate distal ulcerative colitis.\n Thirty-seven patients were randomly assigned to treatment with either rectal mesalamine, 4 g at night, (n = 19) or oral sulfasalazine, 1 g four times a day, (n = 18) in a 6-wk, double-blind, double-dummy, parallel-group, multicenter study. Patients known to be refractory to SAS or 5-ASA preparations were excluded. Efficacy was assessed by a physician-rated Disease Activity Index (DAI), which included symptom evaluations and sigmoidoscopic findings, by physician-rated Clinical Global Improvement (CGI) scores, and by Patient Global Improvement (PGI) scores. Safety was assessed by adverse event reports, clinical laboratory tests, and physical examination. Results. Mean DAI scores indicated significant improvement from baseline in both treatment groups. CGI scores indicated that 94% of the 5-ASA patients were either \"Very Much Improved\" or \"Much Improved\" at wk 6 versus 77% of the SAS patients. PGI ratings showed more improvement in the 5-ASA treatment group than in the SAS group at wk 2 (p = 0.02) and at wk 4 (p = 0.04). Adverse events, primarily headache and nausea, occurred significantly more frequently (p = 0.02) in the SAS than in the 5-ASA group (83 vs 42%). Three patients were withdrawn from SAS treatment because of adverse events.\n Rectally administered 5-ASA is as effective as oral SAS in treatment of active distal ulcerative colitis but is associated with fewer and milder adverse events. Patients treated with 5-ASA reported improvement earlier than those treated with SAS.", "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.", "5-Aminosalicylic acid (5-ASA) is the active component of Salazopyrin and induces a prompt and excellent improvement, when administered as high dosage enema, in patients suffering from active ulcerative colitis. However, the high instability of this metabolite makes its large use difficult. We aimed at finding a more stable preparation and therefore wondered whether another similar molecule, i.e. 4-aminosalicylic acid (4-ASA, generally known as p-aminosalicylic acid, PAS), which differs from 5-ASA only for the position of the amino group, might be a valid alternative. Therefore, 4-ASA at 2 g dosage, administered as rectal enema, was compared to an equivalent preparation of 5-ASA. We carried out a double-blind therapeutical trial, in which 63 patients, similarly matched for age, sex and extent of disease, took part. The analysis of the final results showed that in the 5-ASA group, 26 (81%) out of 32 patients improved clinically, 25 (78%) sigmoidoscopically and 15 (46%) histologically. In the group of the 31 patients treated with 4-ASA, 24 (77%) improved clinically, 24 (77%) sigmoidoscopically and 13 (41%) histologically. Since no difference was registered between the two types of treatment (p = 0.141, X2 test), 4-ASA could be a possible form of treatment for active ulcerative colitis.", "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.", "Oral mesalamine (5-aminosalicylate) is the current standard of care for mild-to-moderate ulcerative colitis. We investigated the efficacy and safety of once daily administration of prolonged-release mesalamine granules in maintenance of remission in patients with quiescent ulcerative colitis, compared with the well established twice daily dosing regimen.\n In this multicenter, randomized, single blind, noninferiority trial, 362 patients with quiescent ulcerative colitis were randomly assigned (1:1) to groups that were given oral mesalamine 2 g, once daily, or 1 g, twice daily, for 12 months. The primary objective was to compare remission rates at 1 year, based on the ulcerative colitis disease activity index score, using Kaplan-Meier methodology.\n At 1 year, 70.9% of the group given 2 g mesalamine once daily remained in remission vs 58.9% of the group given 1 g mesalamine twice daily; this difference was statistically significant (P = .024), indicating the increased efficacy of once daily, compared with twice daily, dosing. Self-reported adherence to therapy, measured by visual analog scale score after 4, 8, and 12 months, was significantly greater in the group given 2 g mesalamine once daily, compared with twice daily, at all but 1 study visit (P < .05). Compliance measured by medication taken was not significantly different between the groups. The difference between the 2 groups in overall incidence of adverse events was not statistically significant (P = .23).\n Patients with ulcerative colitis given prolonged-release oral mesalamine 2 g once daily had better remission rates, acceptability, and self-reported adherence to therapy compared with patients given oral mesalamine 1 g twice daily.", "The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis (UC) began with sulfasalazine and was driven by sulfapyridine toxicity. This convention and the assumption that dosing multiple times a day is necessary to treat UC had not been challenged until recently. This study was conducted to determine the efficacy and safety of once-daily dosing of delayed-release mesalamine (Asacol 400-mg tablets) compared with twice-daily dosing for maintaining remission in UC patients.\n A multicenter, randomized, investigator-blinded, 12-month, active-control trial was conducted to assess the noninferiority of delayed-release mesalamine 1.6-2.4 g/day administered once daily compared with twice daily in patients with mild-to-moderate UC currently in clinical remission. The primary end point was maintenance of clinical remission at month 6.\n A total of 1023 patients were randomized and dosed. The primary objective of noninferiority was met. At month 6, 90.5% of patients receiving once-daily dosing had maintained clinical remission, compared with 91.8% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -2.3 to 4.9). At month 12, 85.4% of patients receiving once-daily dosing had maintained clinical remission, compared with 85.4% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -4.6 to 4.7). Both regimens had low rates of withdrawals as a result of adverse events and serious adverse events.\n Once-daily dosing of delayed-release mesalamine at doses of 1.6-2.4 g/day was shown to be as effective as twice-daily dosing for maintenance of clinical remission in patients with UC.\n 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.", "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.", "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.", "Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear.\n To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine.\n A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multicentre, randomised trial: 49 patients received balsalazide 1.5 g twice daily, 40 received balsalazide 3.0 g twice daily, and 44 received mesalazine 0.5 g three times daily. Efficacy assessments were clinical activity index (CAI) and endoscopic score according to Rachmilewitz, and a histological score. In addition, laboratory tests were performed and urinary excretion of 5-ASA and its metabolite N-Ac-5-ASA was analysed. The study lasted for 26 weeks.\n Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly, pairwise contrasts of the final endoscopic score demonstrated a significant difference (p=0.005) between the two balsalazide treatment groups while differences between either of these two groups and mesalazine were not statistically significant. Patients treated with balsalazide excreted less 5-ASA and N-Ac-5-ASA than patients receiving mesalazine but these differences were not statistically significant. Discontinuation of the trial because of adverse effects occurred in nine patients: three in the balsalazide 1.5 g twice daily group, two in the balsalazide 3.0 g twice daily group, and four in the mesalazine 0.5 g three times daily group. No clinically important new drug safety related findings were identified in this study.\n High dose balsalazide (3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated.", "To compare the safety and efficacy of a pH-sensitive, polymer-coated oral formulation of mesalamine (Asacol, Procter & Gamble Pharmaceuticals, Cincinnati, Ohio) with those of placebo in maintaining remission in patients with ulcerative colitis.\n Multicenter, double-blind, placebo-controlled, randomized clinical trial.\n Eight private practices, five university-based medical centers, and four hospitals or clinics.\n 264 patients with ulcerative colitis that had been maintained in remission for at least 1 month while the patients were receiving stable doses of sulfasalazine or any oral mesalamine product.\n Coated mesalamine at oral dosages of 0.8 g/d or 1.6 g/d or matching placebo for 6 months.\n Treatment success, defined as maintenance of remission after 6 months, and treatment failure, defined as relapse during the study (as indicated by proctosigmoidoscopy at 1, 3, or 6 months of treatment) or withdrawal due to adverse events. Safety was assessed on the basis of laboratory analyses and patient- and investigator-noted adverse events.\n 189 patients were compliant with the protocol for 6 months or stopped receiving therapy because of relapse or adverse events. Of these 189 patients, 25 of the 63 patients (39.7%) in the placebo group had treatment success compared with 40 of the 68 patients (58.8% [95% CI, 46.4% to 71.3%]) in the group receiving mesalamine, 0.8 g/d (P = 0.036) and 38 of the 58 patients (65.5% [CI, 52.4% to 78.6%]) in the group receiving mesalamine, 1.6 g/d (P = 0.006). In the intention-to-treat analysis of all patients, 42 of the 87 patients (48.3%) in the placebo group had treatment success compared with 57 of the 90 patients (63.3% [CI, 52.8% to 73.8%]) in the group receiving mesalamine, 0.8 g/d (P = 0.050) and 61 of the 87 patients (70.1% [CI, 59.9% to 80.3%]) in the group receiving mesalamine, 1.6 g/d (P = 0.005). Age, sex, and race were not found to predict treatment success or failure. The mesalamine tablet was well tolerated, and no clinically significant changes were seen in hematologic, hepatic, or renal laboratory profiles.\n Coated mesalamine at oral dosages of 0.8 g/d and 1.6 g/d is safe and effective in maintaining remission in patients with quiescent ulcerative colitis.", "Thirty patients with distal ulcerative colitis in remission (17 proctitis, 13 proctosigmoiditis) were randomly given either 5-aminosalicylic acid (5-ASA) or placebo suppositories, 400 mg bid. During the 1-yr follow-up, patients were assessed clinically every month, and flexible sigmoidoscopy with a rectal pinch biopsy specimen and laboratory data were carried out every 3 months. Two patients in the 5-ASA group chose to withdraw from the study, one relapsed, and 12 remained in remission. In the placebo group, one patient chose to withdraw, 11 relapsed, and three remained in remission. The cumulative remission rate at the 12th month was 92% in the 5-ASA group and 21% in the placebo group. Log rank test showed a significant difference in the relapse rate between the two groups (chi 2 = 14.26, p less than 0.001). No side effects were observed. We conclude that 5-ASA in suppository form (800 mg/day), administered for 1 yr, is safe and effective in maintaining remission of distal ulcerative colitis.", "The safety and efficacy of Claversal (coated, oral 5-aminosalicylic acid (5-ASA) 0.75 g/day) and sulphasalazine 1.5-2.0 g/day were compared for the maintenance treatment of ulcerative colitis in a 1-year double-blind trial. Three hundred and thirty-four patients, whose disease was controlled on a stable dose of sulphasalazine (1.5-2.0 g/day) for a 1-month pre-trial, entered the study. On entry, patients were assigned in a random manner to continue sulphasalazine or to switch to coated 5-ASA. One hundred and thirty-one patients in the coated 5-ASA group and 142 on sulphasalazine were analysed for efficacy. No significant difference was observed between treatments with respect to the cumulative rate of relapse. Over the 12 months, 30 (28%) of the coated 5-ASA patients versus 29 (23%) of those treated with sulphasalazine had an exacerbation of their disease (log rank test P = 0.7011). The incidence of drug-related adverse events and subsequent withdrawals was similar. The high incidence of side-effects usually associated with sulphasalazine was not observed, probably due to the fact that this population was tolerant of sulphasalazine pre-trial. Of the 37 patients who reported adverse events with previous sulphasalazine therapy, however, only two (8%) of the 24 experienced those events when randomized to coated 5-ASA while five (38%) of the 13 who continued on sulphasalazine reported those same events. Coated 5-ASA is a safe, effective therapy for maintaining ulcerative colitis in remission.", "This prospective trial in patients with left-sided ulcerative colitis evaluated the efficacy and acceptability of biweekly high-dose 5-aminosalicylic acid (5-ASA) enemas (4g/100ml) in maintaining a remission recently induced using daily 5-ASA enemas. Thirty-one patients were randomly assigned, 16 to 5-ASA and 15 to oral sulphasalazine (2g/day), and examined monthly. Sigmoidoscopy was performed \"blind\" at six months or at clinical relapse. Twelve patients on 5-ASA (75%) and nine on sulphasalazine (60%) remained in clinical and endoscopic remission throughout the study (NS), and the survival curve for 5-ASA was better at all points (NS). No patient stopped therapy due to side effects, and all those on 5-ASA chose to continue rectal maintenance therapy after the study. It was concluded that biweekly 5-ASA enemas is at least as effective as oral sulphasalazine in maintaining remission in unselected patients whose remission has been achieve using local therapy.", "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 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.", "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.", "Budesonide is a new corticosteroid with high topical anti-inflammatory activity but little systemic effect. The aim of the present study was to compare the efficacy and safety of budesonide enema (2 mg/100 mL) and 5-ASA enema (mesalazine 1 g/100 mL) given for 4 weeks in the treatment of active distal ulcerative colitis and proctitis.\n Ninety-seven patients were studied in a multicentre single-blind randomized group-comparative trial. The primary efficacy variables were endoscopy and histopathology scores obtained at 0, 2 and 4 weeks. Clinical symptoms were the secondary efficacy variables. Haematology, chemistry and adverse events were the safety variables.\n Budesonide and 5-ASA enemas both resulted in a significant improvement in endoscopy and histopathology scores but no difference could be demonstrated between the two treatment groups. There was also a significant improvement of symptoms (number of bowel movements per day, quality of stools, presence of blood and mucus, and state of well-being) within both groups but no difference between the two treatment groups. The clinical remission rate at 4 weeks was, however, 38% for patients treated with budesonide enema but 60% for those treated with 5-ASA enema (P = 0.03). No adverse events attributed to the study drugs were recorded in either of the groups.\n Budesonide enema 2 mg/100 mL appears to be as efficient and well-tolerated as 5-ASA enema in the treatment of active distal ulcerative colitis and proctitis.", "In a double-blind, single-center, 1-year prospective trial, we compared a pH-dependent Eudragit L-coated formulation of oral 5-aminosalicylic acid (5-ASA) (Claversal), 0.5 g b.i.d., and sulfasalazine (SASP), 1 g b.i.d., in the prophylactic treatment of quiescent ulcerative colitis. Forty-four patients received 5-ASA and 44 received SASP. Clinical, sigmoidoscopic, and histologic findings were assessed at 6 and 12 months. The two groups were comparable in all pretrial characteristics. No significant difference was observed in the relapse rate in the two groups either after 6 months [5-ASA 20.5%, SASP 27.5%, p = 0.32, 95% confidence interval (CI) 0.28 +/- 0.13] or after 12 months (5-ASA 38.4%, SASP 51%, p = 0.18, 95% CI 0.38 +/- 0.1). We conclude that (a) 5-ASA was as effective as SASP in maintaining remission of ulcerative colitis; (b) the relapse rate was, however, higher than expected in both groups; (c) the incidence of side effects was similar with both treatments.", "This study was conducted to assess, in a small sample, the short-term outcomes of once-daily mesalamine versus conventional dosing in maintaining quiescent ulcerative colitis (UC) and to assess adherence rates with both regimens.\n Consecutive patients were randomly assigned to either a once-daily regimen, or they continued current conventional regimen (twice daily or 3 times daily). Patients were assessed at 3 months and 6 months. At each point, a clinical symptom disease score was obtained using patient questionnaires, and medication rates via pharmacy data. Adherence was defined as consumption of >80% of prescribed medication. Information was collected by an investigator blinded to treatment regimen.\n Twenty-two patients were enrolled in the study, 12 in the once-daily group (QD) and 10 in the conventional group (CD). At 3 months, no patients had experienced a relapse. All of the patients in the QD group and 70% of patients in the CD group were adherent (P = 0.04). The average amount of medication consumed in the QD group was significantly higher than in the CD group (90% vs. 75%, P = 0.02). At 6 months, 2 patients (1 patient from each group) experienced a clinical relapse (P = 0.76). Seventy-five percent vs. 70% of patients were adherent (P = 0.8); the amount of medication taken approached significance (90% vs. 76%, P = 0.07). All patients in the QD group reported being either \"very satisfied\" or \"satisfied\" with their regimen.\n In this randomized pilot trial, patients taking once-daily mesalamine had outcomes similar to those for patients on conventional regimens. A larger trial is warranted to assess whether true differences between regimens exist.", "Oral mesalamine (Asacol) in a dose of 3.2 g/day was administered in a 16-week placebo-controlled trial in 38 patients for the treatment of mildly to moderately active Crohn's colitis or ileocolitis. Eighteen patients continued a stable dose of prednisone of no more than 20 mg/day and 20 patients did not take prednisone. Changes in the Crohn's Disease Activity Index (CDAI) were used as the primary measure of efficacy. Oral mesalamine was effective in achieving partial or complete remission in 60% of patients as compared with 22% of placebo-treated patients. However, only 20 of 38 patients completed the 17-week study. The others withdrew early because of worsening of symptoms or were dropouts counted as failures. The high percentage of early withdrawals prevented comparison of mean 17-week CDAI scores. Although the number of patients in this study was relatively small, Asacol 3.2 g/day appears to be safe and effective treatment for mildly to moderately active Crohn's colitis and ileocolitis as compared with placebo, and this regimen is an option for treatment of patients who fail or are intolerant of sulfasalazine.", "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).", "Maintenance treatment in ulcerative colitis should be as convenient as possible, to increase the chance of compliance. MMX mesalazine is a once-daily, high-strength (1.2 g/tablet) formulation of 5-aminosalicylic acid. This study evaluated the safety and efficacy of MMX mesalazine dosed once or twice daily as maintenance therapy in patients with ulcerative colitis.\n This multicentre, randomised, open-label trial enrolled patients with strictly defined clinical and endoscopic remission, immediately following an episode of mild to moderate ulcerative colitis. Patients were randomised to MMX mesalazine 2.4 g/day as a single (2x1.2 g tablet) or divided dose (1x1.2 g tablet twice daily) for 12 months.\n 174 patients (37.9%; safety population n = 459) experienced 384 adverse events, the majority of which were mild or moderate in intensity. Eighteen patients (3.9%), nine in each group, experienced a total of 22 serious adverse events (10 in the once-daily and 12 in the twice-daily group). Most serious adverse events were gastrointestinal, experienced by 5 patients in the once-daily and 4 in the twice-daily group. At month 12, 64.4% (efficacy population, n = 451) of patients in the once-daily and 68.5% of patients in the twice-daily group were in clinical and endoscopic remission (p = 0.351). At month 12, 88.9% and 93.2% in each group, respectively, had maintained clinical remission (were relapse free).\n MMX mesalazine 2.4 g/day administered as a single or divided dose demonstrated a good safety profile, was well tolerated and was effective as maintenance treatment. High clinical and endoscopic remission rates can be achieved with once-daily dosing.\n NCT00151944.", "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.", "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.", "The value of 5-aminosalicylic acid (5-ASA) in Crohn's disease (CD) is still under discussion. In a previous study 2 g 5-ASA per day were inferior to a standard glucocorticoid treatment with 6-methylprednisolone (6-MPred) (Can J Gastroenterol 1990; 4: 446-51). In the present study we tested whether in active CD response rates to 4.5 g 5-ASA/day were not different from those to 6-MPred.\n Multicenter randomized double-blind double-dummy trial. 34 patients with active CD (CDAI > 150) were included. 17 patients were in the 5-ASA group (Salofalk, 4.5 g/day), 17 patients in the 6-MPred group (Urbason, initial dose 48 mg/day, weekly tapering). Duration of treatment was 8 weeks. Main outcome measure was remission of CD (CDAI < 150) and decrease of at least 60 points.\n Both groups were comparable with respect to demographic and clinical parameters. The median CDAI decrease in the 5-ASA group was 85, in the 6-MPred group 122 (p = 0.7437). The median AUC of the CDAI in the 5-ASA group was 1027, in the 6-MPred group 950 (p = 0.137). The median AUC of the CDAI per treatment day was 22.94 in the 5-ASA group, and 17.33 in the 6-MPred group (p = 0.0555). On an intention-to-treat basis remission rates after 8 weeks were 40.0% in the 5-ASA group and 56.3% in the 6-MPred group (p = 0.5867).\n Response rates to 5-ASA or 6-MPred were not significantly different although there was a trend towards a higher efficacy of 6-MPred. 5-ASA may be considered as alternative treatment in patients with activer CD who are intolerant to or refuse glucocorticoids.", "The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX) has been proposed as a novel approach for the treatment of ulcerative colitis (UC).\n To assess the efficacy and the tolerability of 8 weeks' oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates.\n This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS).\n A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005).\n CB-01-05 MMX was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates." ]

[ "1582239", "8093824", "7884017", "12678168", "1681680", "10971979", "7542829", "7041516", "9221965", "6931470", "16754835", "9131723", "12766921", "7041517", "2645508", "17625502" ]

[ "Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.", "A controlled Nordic multicentre study of zuclopenthixol acetate in oil solution, haloperidol and zuclopenthixol in the treatment of acute psychosis.", "A double-blind controlled study of intramuscular zuclopenthixol acetate and liquid oral haloperidol in the treatment of schizophrenic patients with acute exacerbation.", "Comparative study of the effectiveness of zuclopenthixol acetate and haloperidol in acutely disturbed psychotic patients.", "Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study.", "A double blind comparison of zuclopenthixol acetate with haloperidol in the management of acutely disturbed schizophrenics.", "Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double-blind parallel-group trial.", "A double-blind clinical investigation of cis(Z)-clopenthixol and clopenthixol in chronic schizophrenic patients.", "Clozapine versus placebo in Huntington's disease: a double blind randomised comparative study.", "Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate.", "Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder.", "Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study.", "The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia.", "Cis(Z)-clopenthixol and haloperidol in chronic schizophrenic patients--a double-blind clinical multicentre investigation.", "[Comparative double-blind study of the effectiveness and tolerance of baclofen, tetrazepam and tizanidine in spastic movement disorders of the lower extremities].", "Efficacy and safety of donepezil in patients with schizophrenia or schizoaffective disorder: significant placebo/practice effects in a 12-week, randomized, double-blind, placebo-controlled trial." ]

[ "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.", "Zuclopenthixol acetate--a new injectable formulation with a duration of action of 2-3 days--was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed, psychotic patients. The patients were stratified into 3 diagnostic categories: acute psychoses (48 patients), mania (22 patients), and exacerbation of chronic psychoses (73 patients). The patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Mania Rating Scale (BRMAS) (only manic patients) and globally on the Clinical Global Impression (CGI). The study was an open, randomized multicentre trial with a 6-day treatment period. The zuclopenthixol acetate patients received 1-4 doses, the haloperidol patients 1-26 and the zuclopenthixol patients 1-22 doses. The assessments on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories, with no differences between treatments. The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments. All 3 treatments caused a rapid remission of symptoms on the BRMAS. Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments. Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients.", "We carried out a 9-day double-blind clinical trial comparing intramuscular zuclopenthixol acetate with liquid oral haloperidol in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. A parallel-group design was used with stratification by sex. Zuclopenthixol acetate (50 to 150 mg) was given intramuscularly every 3 days, whereas liquid haloperidol (10 to 30 mg daily) was given orally three times a day, with supplementary doses of each medication given under double-blind conditions when needed for agitation. No other sedative drugs, including benzodiazepines, were administered. The mean daily dose was 18.9 mg for haloperidol as compared with a mean dose per 3 days of 117.6 mg for zuclopenthixol. The two treatments were found to be equally efficacious on the Brief Psychiatric Rating Scale and Clinical Global Impression Scale. Both drugs induced similar extrapyramidal side effects. However, more tremors were associated with zuclopenthixol as was a tendency for tardive dyskinesia to be unmasked at the end of the injection interval. Sedation was higher with zuclopenthixol acetate than with haloperidol. Serum creatinine phosphokinase levels were not significantly increased after zuclopenthixol injections. The results of this trial suggest that zuclopenthixol acetate given intramuscularly every second to third day offers an alternative to conventional liquid oral haloperidol in the management of acute schizophrenia.", "To study the effectiveness, frequency of administration and side effects of zuclopenthixol acetate (ZPTA) and haloperidol (HAL) in the treatment of acute psychotic disturbance with aggression.\n Purposive sampling method was employed in a group of psychotic patients with aggression admitted to Songkla Neuropsychiatric Hospital, they were randomly divided into 2 groups: ZPTA group and HAL group. All of the patients were evaluated daily for 7 consecutive days using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale (CGI). Statistical analysis was performed by using the Student t-test and Linear regression.\n There were 70 patients with diagnosis of schizophrenia, mania and acute psychosis. Thirty-eight patients were randomly assigned to the ZPTA group and were given 50-100 mg of the drug, while 32 patients received HAL 5-10 mg. The result showed a significant reduction in BPRS or CGI scores in both groups. Patients treated with ZPTA required less frequent administration than did those on HAL (p < 0.05). There was no statistically significant difference in the reduction in scores between the two groups. Nor was there a statistical difference in reduction of aggression based on BPRS rating. Each group of patients showed a few side effects of mild degree.\n Both ZPTA and HAL were effective in the treatment of acute psychosis with aggression, but frequency of administration was lower in the ZPTA group", "Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.", "The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient. Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were randomised to receive either zuclopenthixol acetate or haloperidol. They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) and UKU Side Effects Scale. Apart from repeat injections of the same medication, no other anti-psychotic was given for the duration of the study. 50 subjects entered the study of which 44 completed. 23 were given zuclopenthixol acetate and 21 haloperidol. Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating (p < 0.001). There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days (p > 0.05). More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study. Both groups had minimal side effects. Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic.", "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 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.", "To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease.\n Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately.\n Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties.\n Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group.", "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.", "Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.\n To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.\n Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).\n Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).\n Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.\n Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.", "Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a \"trait\" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.", "Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design.\n To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone.\n Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted.\n 66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure.\n After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.\n Copyright 2003 John Wiley & Sons, Ltd.", "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.", "In a double-blind comparative study, the therapeutic efficacy and safety of three centrally effective antispasmodics (Tetrazepam, Baclofen and Tizanidine) in patients suffering from multiple sclerosis with spastic motor disturbances of the lower extremities was to be examined. 47 patients of either sex at the age of 23 until 63 were allocated to one of the three therapies by means of minimization. The duration of treatment was limited to 35 days at a maximum. The dosage was optimized corresponding to the clinical symptoms. The antispasmodic efficacy and safety of the above-mentioned substances was investigated with well-established parameters and methods. The typical laboratory parameters were determined at the beginning and at the end of the study. -With reference to cloni, spasms and the muscular tonus, no systematic differences were found between the treatment groups. A previously existing clonus could not be altered decisively by the administration of the three antispasmodics, whereas the muscular tonus could comparably be decreased with all therapeutic measures. Statistically significant differences between the treatment groups were not observed. The patients of all three groups recorded a subjective sensation of relief with reference to the symptoms of spasms by the medication. As to the residual urinary volume, no relevant differences and alterations were determinated in the course of the treatment as well. With reference to undesired side effects quantitative and qualitative differences could be established, in which Tetrazepam showed the most favourable benefit/risk ratio.", "Altered expression of central muscarinic and nicotinic acetylcholine receptors in hippocampal and cortical regions may contribute to the cognitive impairment exhibited in patients with schizophrenia. Increasing cholinergic activity through the use of a cholinesterase inhibitor (ChEI) therefore represents a possible strategy for cognitive augmentation in schizophrenia. We examined the efficacy and safety of the ChEI donepezil as cotreatment for mild to moderate cognitive impairment in schizophrenia or schizoaffective disorder in a prospective, 12-week, placebo-controlled, double-blind, parallel-group study. In total, 250 patients (18-55 years) with schizophrenia or schizoaffective disorder who were clinically stabilized on risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole, alone or in combination, were enrolled at 38 outpatient psychiatric clinics in the United States. Patients were randomized to donepezil 5 mg q.d. for 6 weeks then 10 mg q.d. for 6 weeks, or placebo administered as oral tablets. The primary outcome measure was the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) neurocognitive battery composite score. In the intent-to-treat sample (donepezil, n=121; placebo, n=124), both treatments showed improvement in the composite score from baseline to week 12. At week 12, cognitive improvement with donepezil was similar to that with placebo (last-observation-carried-forward effect size, 0.277 vs 0.411; p=0.1182) and statistically significantly inferior for the observed-cases analysis (0.257 vs 0.450; p=0.044). There was statistically significant improvement in the Positive and Negative Syndrome Assessment Scale negative symptoms score for placebo compared with donepezil, while total and positive symptom scores were similar between both treatments. Statistically significant improvements in positive symptoms score and Clinical Global Impression-Improvement for donepezil compared with placebo were noted at Week 6. Treatment-emergent adverse events (AEs) were observed for 54.5% of donepezil- and 61.3% of placebo-treated patients; most AEs were rated as mild to moderate in severity. Donepezil was safe and well-tolerated but was not effective compared with placebo as a cotreatment for the improvement of cognitive impairment in this patient population. A significant and surprisingly large placebo/practice effect was observed among placebo-treated patients, and is a serious consideration in future clinical trial study designs for potential cognitive enhancing compounds in schizophrenia." ]

[ "3883876", "12785023", "14725657", "2690721", "7740420", "7029140", "12614412", "3307653", "9163286" ]

[ "Varicose veins: optimum compression following sclerotherapy.", "Foam-sclerotherapy, surgery, sclerotherapy, and combined treatment for varicose veins: a 10-year, prospective, randomized, controlled, trial (VEDICO trial).", "Evaluation of the efficacy of polidocanol in the form of foam compared with liquid form in sclerotherapy of the greater saphenous vein: initial results.", "Varicose veins: optimum compression after surgery and sclerotherapy.", "Mesocaval shunt or repeated sclerotherapy: effects on rebleeding and encephalopathy--a randomized trial.", "A random controlled trial of two forms of compression bandaging in outpatient sclerotherapy of varicose veins.", "Ambulatory phlebectomy versus compression sclerotherapy: results of a randomized controlled trial.", "Shunt surgery versus endoscopic sclerotherapy for long-term treatment of variceal bleeding. Early results of a randomized trial.", "Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial." ]

[ "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.", "The study compared, by a prospective, randomized method, 6 treatment options: A: Sclerotherapy; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclerotherapy; F: Surgery (ligation) followed by sclerotherapy. Results were analyzed 10 years after inclusion and initial treatment. Endpoints of the study were variations in ambulatory venous pressure (AVP), refilling time (RT), presence of duplex-reflux, and number of recurrent or new incompetent venous sites. The number of patients, limbs, and treated venous segments were comparable in the 6 treatment groups, also comparable for age and sex distribution. The occurrence of new varicose veins at 5 years varied from 34% for group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins varied from 37% in F to 56% in A. At inclusion AVP was comparable in the different groups. At 10 years the decrease in AVP and the increase in RT (indicating decrease in reflux), was generally comparable in the different groups. Also at 10 years the number of new points of major incompetence was comparable in all treatment groups. These results indicate that, when correctly performed, all treatments may be similarly effective. \"Standard,\" low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain, in selected subjects, results comparable to surgery.", "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.", "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.", "Sclerotherapy is usually effective in controlling acutely bleeding esophageal varices. It may not be as effective as shunt surgery for prevention of rebleeding; therefore we undertook a prospective study comparing interposition mesocaval shunt (MCS) and repeated sclerotherapy.\n Forty-five patients (mean age, 52.6 +/- 9.8 years) with variceal bleeding were randomized after emergency endoscopic sclerotherapy either to repeat variceal obliteration followed by regular check endoscopy (n = 21) or to elective interposition mesocaval shunting by use of 14 mm polytetrafluoroethylene graft (n = 24). There was an equal distribution of Child's classes in the two groups.\n In the sclerotherapy group 12 patients had recurrent hemorrhages causing five deaths compared with the shunt group, in which four patients had postoperative bleeding but without associated death. No difference was noted in the incidence of encephalopathy despite the development of total shunting 1 year after MCS. The median hospital stay was similar; 34.5 days (MCS) and 33 days (sclerotherapy). The number of intensive care unit days was also similar in the two groups. No difference was noted in survival in patients with Child's A and Child's B disease in the treatment groups. In patients with Child's C cirrhosis there was a statistically significant longer survival in patients undergoing MCS compared with patients undergoing sclerotherapy.\n The results of the study show that the rate of rebleeding is significantly higher after sclerotherapy than after mesocaval shunting. In patients with Child's C cirrhosis MCS may be an alternative to sclerotherapy for the prevention of rebleeding from esophageal varices in patients not suitable for transplantation.", "nan", "Although no randomized controlled trial has assessed the effects of either compression sclerotherapy or ambulatory phlebectomy, both techniques are used to treat varicose veins worldwide. We performed a randomized controlled trial to compare recurrence rates of varicose veins and complications after compression sclerotherapy and ambulatory phlebectomy.\n From September 1996 to October 1998, we randomly allocated 49 legs to compression sclerotherapy and 49 legs to ambulatory phlebectomy. Our primary outcome parameters were as follows: recurrence rates at 1 and 2 years and complications related to therapy. Eighty-two patients were included, of whom 16 were included with both of their legs. The number of treated legs was therefore 98, but two patients were lost to follow-up.\n One year recurrence amounted to 1 out of 48 for phlebectomy and 12 out of 48 for compression sclerotherapy (P<0.001); at 2 years, six additional recurrences were found, but then solely for compression sclerotherapy (P<0.001). Significant differences in complications occurring more in phlebectomy than in compression sclerotherapy therapy were blisters, teleangiectatic matting, scar formation, and bruising from bandaging.\n Our results show that ambulatory phlebectomy is an effective therapy for varicose veins of the leg. Recurrence rates are significantly lower than for compression sclerotherapy therapy. If varicose veins persist 4 weeks after compression sclerotherapy, it can be argued that to reduce the risk of future recurrence ambulatory phlebectomy should be considered as the better treatment option.", "In September 1982, a prospective randomized trial comparing shunt surgery and endoscopic sclerotherapy for the elective management of variceal hemorrhage in patients with cirrhosis was initiated. Twenty-seven patients have received shunts (distal splenorenal = 23, nonselective = 4) and 30 patients have had chronic sclerotherapy. Eighty-six per cent of patients had alcoholic cirrhosis and 33% were Child's class C. After a mean follow-up of 25 months, 19% of shunt and 57% of sclerotherapy patients have had rebleeding (p = 0.003). Kaplan-Meier survival analysis reveals similar 2-year survival rates for shunt (65%) and sclerotherapy (61%) groups. Only two of 10 sclerotherapy failures have been salvaged by surgery. Posttherapy quantitative hepatic function, frequency of encephalopathy, and cumulative medical costs were similar for both groups. Hepatic portal perfusion and portal pressure at 1 year were better maintained by sclerotherapy than by distal splenorenal shunt. In conclusion, endoscopic sclerotherapy and shunt surgery provide similar results with respect to survival, hepatic function, frequency of encephalopathy, and costs. Sclerotherapy is an acceptable, but not superior, alternative to shunt surgery for treatment of variceal hemorrhage.", "Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency.\n To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices.\n Randomized, controlled clinical trial.\n Three teaching hospitals.\n 49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS.\n Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein.\n Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs.\n Mean follow-up (+/-SE) was 567 +/- 104 days in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]).\n In obliterating varices and reducing rebleeding events from esophageal varies, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant." ]

[ "15017504", "9691103" ]

[ "Budesonide versus mesalamine for maintaining remission in patients refusing other immunomodulators for steroid-dependent Crohn's disease.", "A comparison of budesonide and mesalamine for active Crohn's disease. International Budesonide-Mesalamine Study Group." ]

[ "To compare the efficacy of controlled-release budesonide capsules with that of mesalamine for maintaining remission and improving quality of life (QOL) in patients with steroid-dependent Crohn's disease.\n Fifty-seven patients (25 men; mean age, 32 +/- 10.1 yr) with quiescent steroid-dependent Crohn's ileitis, ileocolitis, or colitis (Crohn's disease activity index <150) entered a prospective, investigator-blind trial. Patients were eligible for treatment with azathioprine but had not consented or had developed side effects. Patients were randomized to receive budesonide 6 mg/day (n = 29) or mesalamine 1 g 3 times/day (n = 28). Follow-up assessments were made every 2 months for up to 1 year or until relapse. At each visit, quality of life (QOL) was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ).\n There were no significant differences in baseline clinical characteristics between the study groups. The 1-year relapse rate was significantly lower in the budesonide group than in the mesalamine group (55% vs. 82%; 95% confidence interval, 12.4%-41%; P = 0.045). Patients assigned to budesonide also remained in remission longer (241 +/- 114 days vs. 147 +/- 117 days; 95% confidence interval, 32.7-155.3 days; P = 0.003). Compared with mesalamine, budesonide treatment also was associated with a better QOL throughout the study (mean total IBDQ scores 165 +/- 36 vs. 182 +/- 28, respectively; 95% confidence interval, -0.4 to 34.4, P = 0.0001). This advantage was confirmed in patients' self-assessed QOL scores.\n Over a 1-year period, controlled-release budesonide was significantly more effective than mesalamine for maintaining remission and improving the QOL of patients with steroid-dependent Crohn's disease.", "Crohn's disease is often treated with glucocorticoids or mesalamine. We compared the efficacy and safety of controlled-ileal-release budesonide capsules and slow-release mesalamine tablets in patients with active Crohn's disease affecting the ileum, the ascending colon, or both.\n In a double-blind, multicenter trial, we enrolled 182 patients with scores of 200 to 400 on the Crohn's Disease Activity Index (with higher scores indicating greater disease activity) and randomly assigned 93 to receive 9 mg of budesonide once daily and 89 to receive 2 g of mesalamine twice daily for 16 weeks. The primary efficacy variable was clinical remission, defined as a score of 150 or less on the Crohn's Disease Activity Index.\n In the analysis of all patients who received at least one dose of study drug, the rates of remission after 8 weeks of treatment were 69 percent in the budesonide group and 45 percent in the mesalamine group (P=0.001); the respective rates after 16 weeks of treatment were 62 percent and 36 percent (P<0.001). Seventy-seven patients in the budesonide group completed the 16 weeks of treatment, as compared with 50 patients in the mesalamine group (P<0.001). The numbers of patients with adverse events were similar in the two groups, but those assigned to budesonide had fewer severe adverse events. Among patients who completed 16 weeks of treatment, the morning plasma cortisol value was normal in 67 percent of budesonide-treated patients and 83 percent of mesalamine-treated patients (P=0.06); 90 percent and 100 percent, respectively, had normal increases in cortisol in response to cosyntropin (P=0.02).\n In patients with active Crohn's disease affecting the ileum, the ascending colon, or both, a controlled-ileal-release formulation of budesonide was more effective in inducing remission than a slow-release formulation of mesalamine." ]

[ "18569754", "3941301", "3812046", "16766441", "1873454", "3716918", "3369332", "17074945", "19524389" ]

[ "Hypnosis for smoking cessation: a randomized trial.", "A randomized controlled trial of hypnotherapy for smoking cessation.", "Treatment effectiveness of hypnosis and behaviour therapy in smoking cessation: a methodological refinement.", "Intensive hypnotherapy for smoking cessation: a prospective study.", "A randomized trial of smoking cessation interventions in general practice in Italy.", "Hypnosis and behavioral treatment in a worksite smoking cessation program.", "Use of single session hypnosis for smoking cessation.", "A randomized controlled trial of a smoking cessation intervention among people with a psychotic disorder.", "Impact of a brief motivational smoking cessation intervention the Get PHIT randomized controlled trial." ]

[ "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.", "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.", "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).", "The purpose of this study was to examine the effectiveness of different practice-based approaches to assist patients of primary care physicians to quit smoking and sustain cessation. Forty-four nonsmoking general practitioners volunteered for the study. After a period of training, they randomized 923 smoking clients, unselected for motivation toward quitting, to four different intervention groups: (i) minimal intervention, consisting of one single counselling session and a brief handout on quitting techniques; (ii) repeated counselling including reinforcing sessions at Months 1, 3, 6, and 9; (iii) repeated counselling and use of nicotine gum; and (iv) repeated counselling and spirometry. Biochemically validated smoking status was assessed at six and 12 months after recruitment. The proportion of verified quitters at 12 months was 4.8 percent among subjects randomized to the minimal intervention group, compared to 5.5 percent, 7.5 percent, and 6.5 percent among those randomized to the three repeated-counselling groups. In no treatment group was the outcome significantly different from that for one-time counselling at the (P less than 0.05) level. Lack of power, contamination, and low attendance at reinforcing sessions should be taken into account in interpreting the results.", "In the initial study, 48 subjects of the total (N = 63) ultimately used, were assigned to one of three treatments: four hypnotic sessions with a booster, two hypnotic sessions, or two hypnotic and two behavioral sessions with a booster. A follow-up group was later recruited composed of 15 subjects who received four hypnotic sessions and a booster session with less time between sessions. The results indicated no difference in smoking cessation 6 months after treatment regardless of the frequency, length between sessions, or addition of behavioral methods. Successful subjects were more educated, less able to utilize their imagination, and had fewer smokers at home.", "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.", "Despite extremely high rates of smoking among individuals with psychotic disorders and the associated financial and health costs, few studies have investigated the efficacy of smoking cessation interventions among this group. The purpose of this study was to compare an integrated psychological and nicotine replacement therapy intervention for people with a psychotic disorder with routine care alone.\n The authors recruited 298 regular smokers with a psychotic disorder residing in the community and randomly assigned them to a routine care comparison condition (N=151) or an eight-session, individually administered smoking cessation intervention (N=147), which consisted of nicotine replacement therapy, motivational interviewing, and cognitive behavior therapy. Outcome variables included continuous and point-prevalence abstinence rates, smoking reduction status, and changes in symptoms and functioning.\n While there were no overall differences between the treatment group and comparison group in abstinence rates, a significantly higher proportion of smokers who completed all treatment sessions stopped smoking at each of the follow-up occasions (point-prevalence rates: 3 months, 30.0% versus 6.0%; 6 months, 18.6% versus 4.0%; and 12 months, 18.6% versus 6.6%). Smokers who completed all treatment sessions were also more likely to have achieved continuous abstinence at 3 months (21.4% versus 4.0%). There was a strong dose-response relationship between treatment session attendance and smoking reduction status, with one-half of those who completed the intervention program achieving a 50% or greater reduction in daily cigarette consumption across the follow-ups, relative to less than one-fifth of the comparison subjects. There was no evidence of any associated deterioration in symptoms or functioning.\n These findings demonstrate the utility of a nicotine replacement therapy plus motivational interviewing/cognitive behavior therapy smoking cessation intervention among individuals with a psychotic disorder. Further development of more efficacious interventions is required for those who do not respond to existing interventions.", "Few studies have rigorously evaluated whether providing biologically based health-risk feedback is more effective than standard interventions in increasing smokers' motivation to quit and their long-term abstinence.\n An RCT was conducted from 2005 to 2008. Data were analyzed in 2008.\n Smokers (N=536) were recruited from the community, regardless of their interest in quitting smoking.\n Smokers either received brief ( approximately 20 minutes), personally tailored counseling sessions based on their lung functioning, carbon monoxide (CO) exposure, and smoking-related health conditions, or they received generic smoking-risk information and personalized counseling about their diet, BMI, and physical activity. All were advised to quit smoking and were offered access to a free phone-counseling program.\n Treatment utilization and abstinence at 6 and 12 months post-intervention.\n Participants who received the experimental treatment demonstrated no greater motivation to quit, use of treatment services, or abstinence compared to controls at either follow-up assessment. In fact, controls reported greater motivation to quit at 12 months (M 3.42 vs 3.20, p=0.03), greater use of pharmacotherapy at 6 months (37.8% vs 28.0%, p=0.02), and greater 30-day point prevalent abstinence at 6 months, after controlling for relevant covariates (10.8% vs 6.4%, adjusted p=0.04).\n The present study found no support for adding a personalized health-risk assessment emphasizing lung health and CO exposure to generic cessation advice and counseling for community-based smokers not otherwise seeking treatment.\n NCT00169260." ]

[ "1670783", "17710485" ]

[ "Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial.", "Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization." ]

[ "We tested the hypothesis that antihistamine-decongestant combinations cause no clinically significant relief of the symptoms of upper respiratory tract infections in young children by randomly assigning 96 children to one of three treatment groups: antihistamine-decongestant, placebo, and no treatment. There were no differences among the three study groups in the proportion of children considered \"better\" overall by the parent 48 hours after the initial assessment (drug, 67%; placebo, 71%; no treatment, 57%; p = 0.53). There were no differences among groups in individual or composite symptom score changes. Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms. In the proportion of parents believing that their child needed medicine, there was no difference between those who consented to participate and those who refused. Parents who wanted medicine at the initial visit reported more improvement at follow-up, regardless of whether the child received drug, placebo, or no treatment. We conclude that there is no clinically significant improvement in symptoms of upper respiratory tract infection, including no significant placebo effect, in young children for whom an antihistamine-decongestant is prescribed.", "Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.\n The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.\n An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.\n Thirty-one adult CAP patients who required hospitalization were enrolled.\n Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.\n In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy." ]

[ "8331703", "19477503", "9161392", "6195948", "8598656", "3672322", "6733063", "7717832", "8129501", "6998538", "11001889", "15457363", "17177928", "861482", "9160697", "15699762" ]

[ "Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups.", "Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial.", "A randomized, prospective trial of deep venous thrombosis prophylaxis in aortic surgery.", "Prevention of postoperative deep venous thrombosis and pulmonary emboli with combined modalities.", "Is DVT prophylaxis overemphasized? A randomized prospective study.", "Regimen for improved effectiveness of intermittent pneumatic compression in deep venous thrombosis prophylaxis.", "The efficacy of graduated compression stockings in the prevention of deep vein thrombosis after major gynaecological surgery.", "Deep vein thrombosis: prevention in stroke patients during rehabilitation.", "Changing clinical practice. Prospective study of the impact of continuing medical education and quality assurance programs on use of prophylaxis for venous thromboembolism.", "Low dose heparin and compression stockings in the prevention of postoperative deep venous thrombosis.", "Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study.", "Venous thromboembolism prophylaxis after head and spinal trauma: intermittent pneumatic compression devices versus low molecular weight heparin.", "Adoption of a ventilator-associated pneumonia clinical practice guideline.", "The efficacy of graduated compression stockings in the prevention of deep vein thrombosis.", "Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial.", "Valacyclovir for cytomegalovirus prophylaxis reduces the risk of acute renal allograft rejection." ]

[ "The incidence of deep venous thrombosis (DVT) and the efficacy of prophylactic measures were prospectively evaluated in all patients admitted to a level I trauma center during 1991. Patients with Injury Severity Scores (ISS) > 9 who survived a minimum of 48 hours (n = 395) were monitored using venous Doppler and ultrasound studies during hospitalization (total, 1308 studies). Two hundred eighty-one patients (71%) were randomly assigned to low-dose heparin or sequential compression devices. There were 18 cases of lower extremity DVT (4.6%) and four cases (1.0%) of pulmonary emboli (PE), three of which were fatal. Eight patients (2.9%) on prophylaxis and 10 (8.8%) without prophylaxis developed DVT (p < 0.02 by Chi-square). There were two PEs in each group. Fourteen of these 18 patients sustained blunt trauma and included seven spinal fractures or subluxations (four paraplegic) and four severe head injuries. This represented 14.0% of 50 patients admitted with spinal injuries and 4.3% of 92 patients with severe head injuries. Compared with those with no neurologic injury (7 of 253 or 2.7%), the risk of DVT is significantly higher in the spinal injury patients (p < 0.001, Chi-square) and twice as high as in the head injury group, although not statistically significant (p = 0.4, Chi-square). Three of the four patients with penetrating trauma and DVT had venous injuries. We conclude that DVT prophylaxis can significantly reduce the incidence of DVT in trauma patients with ISS > 9. Patients with severe neurologic injuries (particularly spinal cord) are at high risk for DVT and PE and may be considered for a prophylactic Greenfield filter.", "Deep vein thrombosis (DVT) and pulmonary embolism are common after stroke. In small trials of patients undergoing surgery, graduated compression stockings (GCS) reduce the risk of DVT. National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence. We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke.\n In this outcome-blinded, randomised controlled trial, 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK, Italy, and Australia. Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7-10 days and, when practical, again at 25-30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is registered, number ISRCTN28163533.\n All patients were included in the analyses. The primary outcome occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio 4.18, 95% CI 2.40-7.27).\n These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results.\n Medical Research Council (UK), Chief Scientist Office of Scottish Government, Chest Heart and Stroke Scotland, Tyco Healthcare (Covidien) USA, and UK Stroke Research Network.", "To study the incidence of postoperative deep venous thrombosis (DVT) in patients undergoing elective aortic reconstruction and to determine if aggressive DVT prophylaxis would reduce the incidence of DVT in these patients.\n Randomized, prospective trial.\n University hospital and Veterans Affairs hospital.\n One hundred patients undergoing aortic reconstruction for aneurysmal or occlusive disease randomized to receive DVT prophylaxis (treatment group) or no prophylaxis (control group). Exclusion criteria included a history of DVT, long-term anticoagulant use, or a malignant neoplasm. During the study period, 12 patients were ineligible for follow-up. Ninety-eight patients completed the trial, including 50 patients in the treatment group and 48 patients in the control group. Two patients in the control group died postoperatively of unrelated causes.\n Patients in the treatment group received DVT prophylaxis using a combination of low-dose heparin sodium therapy (5000 U every 12 hours) and calf-length intermittent mechanical compression devices. Control patients received no DVT prophylaxis.\n The occurrence of acute lower extremity DVT diagnosed by interval venous duplex ultrasound scan surveillance performed on postoperative days 1, 3, and 7.\n The overall incidence of proximal DVT in this study was 2%. One case of DVT occurred in the treatment group, and the other one occurred in the control group. There was no statistically significant difference (P = .99) in the incidence of DVT between the 2 groups. One patients in the control group had a nonfatal pulmonary embolus (1% of the patients overall).\n The incidence of proximal DVT in patients undergoing elective aortic reconstruction is low compared with patients undergoing other major intraabdominal general surgical procedures. The use of aggressive DVT prophylaxis did not reduce the risk of postoperative proximal DVT in this study. The selective use of DVT prophylaxis in patients undergoing elective aortic surgery should be based on associated concomitant or evolving risk factors.", "Worldwide statistics reveal that 25 to 40 per cent of patients who are over the age of 40 years and operated on for 1 or more hours will develop a deep venous thrombosis (DVT). The studies reviewed in this paper were performed to evaluate several modalities and compare their effectiveness in preventing DVT in postoperative patients. In the first study, five modalities plus a control group were evaluated in 562 patients from five surgical specialties. The incidence of DVT in the control group was 35 per cent. Though most of the pharmacologic agents were effective in reducing the incidence of DVT, the antistasis devices (gradient elastic stockings and intermittent pneumatic compression) were most effective. The purpose of the second study was to evaluate the effectiveness of combining a pharmacologic drug with an antistasis modality. Deep venous thrombosis was virtually eliminated in this group of 328 patients. There was only a 1.5 per cent incidence of DVT in the treated population as compared to a 26.8 per cent incidence in the control group. Thus, it seems that combining one antistasis and one pharmacologic agent greatly reduces the incidence of lower extremity thrombi. I-125 fibrinogen scanning was the most sensitive test in detecting DVT and had an accuracy of 97 per cent.", "This study was designed to prospectively evaluate a previously published prognostic index for predicting deep venous thrombosis (DVT) in general surgical patients with conventional prophylaxis. Patients undergoing procedures of at least 1 hr duration (abdominal, thoracic, head and neck, inguinal) requiring general or spinal anesthetic were prospectively randomized into the following groups: Group 1, sequential pneumatic compression devices during surgery and 2 days postoperatively; Group 2, subcutaneous heparin (5000 U q 12 hr) starting 1 hr before surgery and for 7 days postop; Group 3, control group. All patients underwent duplex evaluation of bilateral lower extremity deep venous systems preoperatively and on postoperative Days 1, 3, and 30. In addition, a previously developed predictive DVT incidence indicator, the prognostic index (PI), was calculated for each patient. A total of 137 patients were entered into the study with 29 removed for patient/staff reasons. There were no differences in PI among the three groups at the 0.05 level (ANOVA). The distribution of risk factors for DVT including increased age, body size, hemoglobin (Hb), and colorectal procedures were distributed evenly among the groups. Additional factors such as diabetes, COPD, PVD, immobilization, and cancer were also evenly distributed among the groups. The PI predicted a 20% incidence of DVT. For Groups 1 (n = 25), 2 (n = 38), and 3 (n = 45) no DVTs were detected over the 30 days of study. During the study period, 8 DVTs were detected by duplex evaluation in general surgical patients not in the study (1.5%). In conclusion, in a prospective randomized study using sequential pneumatic compression devices, subcutaneous heparin or no prophylaxis in matched general surgical patients at moderate to high risk for thromboembolism, no DVTs occurred for up to 30 days. Furthermore, neither a PI nor other factors associated with DVT accurately predicted the incidence of DVT in this patient population.", "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.", "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.", "Deep vein thrombosis (DVT) and subsequent pulmonary embolism (PE) is a major source of mortality and morbidity in stroke patients. This study was designed to determine the effectiveness of different prophylactic treatments in the prevention of DVT after a stroke in patients undergoing rehabilitation. An additional objective was the identification of risk factors for DVT in stroke in patients during rehabilitation. Three hundred and sixty patients, over a 3-year period, were randomly assigned to one of four groups: adjusted dose heparin, intermittent pneumatic compression (IPC), functional electrical stimulation (FES), or control. There was no significant difference in the development of DVT by treatment group. Patients with DVT on admission (prevalent, n = 61) were compared with the study patients (n = 360). Time interval (from stroke to admission) and lactic dehydrogenase (LDH) concentration were significant risk factors, as well as predictors, for development of DVT (p < .000). These results suggest that the longer a patient remains without DVT prophylaxis after a stroke, the greater the risk of developing DVT and this supports early prophylaxis before rehabilitation.", "To determine the effect of continuing medical education (CME) with and without a quality assurance component (CME+QA) on physician practices in the prevention of venous thromboembolism.\n A communitywide study was performed in 15 short-stay hospitals in central Massachusetts. The study population included 3158 patients in acute-care hospitals with multiple risk factors for venous thromboembolism. Study hospitals were randomly assigned to one of two educational strategies or to a control group that received no intervention.\n The proportion of patients at high risk for venous thromboembolism who received effective methods of prophylaxis increased significantly from 29% in 1986 to 52% in 1989 (P < .001). This increase was seen in all study groups: control hospitals, 40% to 51% (P < .001); CME hospitals, 21% to 49% (P < .0001); and CME+QA hospitals, 27% to 55% (P < .0001). The increase in prophylaxis use from 1986 to 1989 was significantly greater among patients cared for in hospitals whose physicians participated in a formal CME program (an increase of 28%) than in control hospitals (an increase of 11%) (P < .001). There was no significant difference in the use of prophylaxis in hospitals whose physicians received CME+QA interventions compared with hospitals whose physicians received CME interventions alone (identical increases of 28%).\n A formal CME program significantly increased the frequency with which physicians prescribed prophylaxis for venous thromboembolism. We believe the key factor in our CME interventions that motivated clinicians to change their practices was the provision of hospital-specific data demonstrating a compelling need for improvement. Despite the substantial investment by hospitals in QA, traditional QA intervention appeared to provide no additional benefit. Even after extensive CME/QA interventions, prophylaxis for venous thromboembolism remained underutilized, suggesting the need to develop new approaches to changing clinical practice.", "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.", "The role of corticosteroids in the prophylaxis of graft-versus-host disease (GVHD) is not well established. We have conducted a prospective, randomized, open-label, single-center study about the effect of adding methylprednisolone (MP) to the widely used prophylactic regimen consisting of cyclosporine A and methotrexate. A total of 108 consecutive patients treated with allogeneic bone marrow transplantation from an HLA-identical sibling donor for malignant blood disease were entered into the study; 53 patients were randomized to receive and 55 were randomized not to receive prophylactic MP. The dose of MP was 0.5 mg/kg on days 14 to 20, 1 mg/kg on days 21 to 34, 0.5 mg/kg on days 35 to 48, and thereafter the dose was slowly tapered and the administration discontinued on day 110. In the group given prophylactic MP, the incidence of acute GVHD was lower (19% vs 56%, P =.0001), there was a trend toward a lower incidence of chronic GVHD among low-risk patients (P =.06), and during the first 4 months the time spent at hospital was shorter and there were fewer infections. The total amount of MP given was similar in the study groups because of a higher incidence of acute GVHD and its treatment in the group of patients not given prophylactic MP. There were no significant differences between the study groups in relapse rate or survival. In conclusion, the addition of MP to the combination of cyclosporine and methotrexate markedly reduced the incidence of acute GVHD without causing untoward effects. The timing of corticosteroid administration is probably important for the efficacy.", "Although there are alternative methods and drugs for preventing venous thromboembolism (VTE), it is not clear which modality is most suitable and efficacious for patients with severe (stable or unstable) head/spinal injures. The aim of this study was to compare intermittent pneumatic compression devices (IPC) with low-molecular-weight heparin (LMWH) for preventing VTE. We prospectively randomized 120 head/spinal traumatized patients for comparison of IPC with LMWH as a prophylaxis modality against VTE. Venous duplex color-flow Doppler sonography of the lower extremities was performed each week of hospitalization and 1 week after discharge. When there was a suspicion of pulmonary embolism (PE), patients were evaluated with spiral computed tomography. Patients were analyzed for demographic features, injury severity scores, associated injuries, type of head/spinal trauma, complications, transfusion, and incidence of deep venous thrombosis (DVT) and PE. Two patients (3.33%) from the IPC group and 4 patients (6.66%) from the LMWH group died, with their deaths due to PE. Nine other patients also succumbed, unrelated to PE. DVT developed in 4 patients (6.66%) in the IPC group and in 3 patients (5%) in the LMWH group. There was no statistically significant difference regarding a reduction in DVT, PE, or mortality between groups ( p = 0.04, p > 0.05, p > 0.05, respectively). IPC can be used safely for prophylaxis of VTE in head/spinal trauma patients.", "The Academic Center for Evidence-based Practice (ACE) Star Model was used to implement an evidence-based clinical practice guideline (CPG) in order to decrease ventilator-associated pneumonia (VAP) incidence rates and ventilator days. The goal was to interrupt person-to-person transmission of bacteria and bacterial colonization using low-cost, evidence-based strategies to prevent VAP. DISCOVERY: Two geographically proximate medical centers, inclusive of five intensive care units located in the southwestern region of the United States had significant variations in their VAP rates.\n Using the U.S. Preventive Services Task Force grading criteria, the results of 69 studies were used to establish a clinical practice guideline to prevent ventilator-associated pneumonia. TRANSLATION: A clinical practice guideline was developed for the prevention of VAP and included five nursing activities: (a) head-of-bed elevation; (b) oral care; (c) ventilator tubing condensate removal; (d) hand hygiene; and (e) glove use. The effect of the CPG, inclusive of an educational intervention, was measured using an observational, prospective, quasi-experimental design. INTEGRATION: A multidisciplinary education team developed a self-learning packet, educational materials, and storyboards for the staff as dissemination strategies. Strategies also included e-mail, one-on-one teaching with clinicians, and feedback on guideline adoption and VAP rate reports.\n Observation data were collected to evaluate adoption of the CPG while caring for 106 ventilated patients. VAP rates changed at both hospitals although the change was not statistically significant. Additionally, the ICU length of stay declined at both facilities, causing cost savings.\n These results support the idea that adoption of evidence-based practices contributes to decreased VAP rates. For a successful program, ICU leaders should emphasize strategies that routinize adoption of evidence-based CPGs.", "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.", "Patients with a lymphohematopoietic malignancy considered to be at high risk for posttransplant relapse were enrolled in a study to compare the use of cyclosporine (CSP) as a single agent with a combination of methylprednisolone (MP) and CSP for graft-versus-host disease (GVHD) prophylaxis after marrow transplantation from an HLA-identical sibling donor. Sixty patients were randomized to receive CSP only and 62 were randomized to receive CSP plus MP. Daily CSP was started on day -1 (5 mg/kg/d intravenously) and administered at gradually reduced doses until day 180. MP was started on day 7 at 0.5 mg/kg/d, increased to 1.0 mg/kg/d on day 15, started on a taper schedule on day 29, and discontinued on day 72. All 104 evaluable patients (surviving > or =28 days) had sustained engraftment. The incidence rates of grades II-IV acute GVHD were 73% and 60% for patients receiving CSP and CSP plus MP, respectively (P = .01). No difference was seen for grades III-IV GVHD. However, chronic GVHD occurred somewhat more frequently in patients receiving CSP plus MP (44%) than in patients receiving only CSP (21%; P = .02). The incidence of de novo chronic GVHD was marginally higher in patients receiving CSP plus MP (P = .08). No significant differences in the risk of infections were observed. There was a suggestion that the risk of relapse was lower in patients receiving CSP plus MP (P = .10) and, although the overall survival in the two groups was not different (P = .44), there was a slight advantage in favor of CSP plus MP-treated patients for relapse-free survival (P = .07). These results suggest that prophylactic MP, when combined with CSP, has only limited efficacy in acute GVHD prevention and may increase the probability of chronic GVHD.", "Both oral ganciclovir and valacyclovir decrease the incidence of cytomegalovirus (CMV) disease after renal transplantation. Moreover, valacyclovir has been shown to reduce the risk of acute rejection. Our study was designed to compare the efficacy and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease after renal transplantation.\n A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir (8 g/day, n=35, VAL). A control group (DEF, n=12) was managed by deferred therapy.\n No differences were found in demography, immunosuppression, or donor/recipient CMV serology. The 12-month incidence of CMV disease was 67% in the DEF group compared with 6% in the GAN group and 3% in the VAL group (P<0.001 GAN or VAL vs. DEF; P=0.575 GAN vs. VAL). The biopsy-confirmed acute rejection rate at 12 months was 12% in the VAL group compared with 34% in the GAN group (P=0.030) and 58% in the DEF group (P<0.001). The difference between the GAN and DEF groups was not significant (P=0.087). The average CMV-associated costs per patient were $3,072, $2,906, and $4,906 in the GAN, VAL, and DEF groups, respectively.\n Valacyclovir and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation. Both regimens are cost-effective. Valacyclovir is associated with a significantly reduced risk of acute rejection compared with both ganciclovir prophylaxis and deferred therapy." ]

[ "75438", "8142334", "3089466", "2754147" ]

[ "A double-blind controlled crossover trial of an antigen-avoidance diet in atopic eczema.", "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.", "Effect of maternal dietary exclusion on breast fed infants with eczema: two controlled studies.", "Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study." ]

[ "20 out of 36 children (aged two to eight years) with atopic eczema completed a twelve-week, double-blind, controlled, crossover trial of an egg and cows' milk exclusion diet. During the first and third four-week periods, patients on an egg and cows' milk exclusion diet received a soya-based milk substitute (trial period) or an egg and cows' milk preparation (control period). Response was assessed in terms of eczema activity, number of areas affected, pruritus, sleeplessness, and antihistamine usage while on the two diets. During the middle period patients resumed their normal diet to minimise any carry-over effect. 14 patients responded more favourably to the antigen-avoidance diet than to the control diet, whereas only 1 responded more favourably to the control diet than the trial diet. Patients experienced more benefit during the first diet period than the second, whatever the nature of the diet. There was no correlation between a positive prick test to egg and cows' milk antigen and response to the trial diet.", "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.", "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.", "The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cow's milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cow's milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group (p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life." ]

[ "7972781", "9159625", "1987387", "16765759", "15489085", "10514159" ]

[ "Low-dose aspirin combined with dipyridamole versus anticoagulants after femoropopliteal percutaneous transluminal angioplasty.", "Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical prosthetic heart valves.", "Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.", "Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial.", "Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.", "Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin." ]

[ "To investigate whether anticoagulation or platelet inhibition treatment provides better prevention of reobstruction after percutaneous transluminal angioplasty (PTA).\n In a controlled study, 160 patients received either oral anticoagulants or a combination of low-dose acetylsalicylic acid (25 mg) and dipyridamole (200 mg) (ASAD) twice daily for 1 year after successful femoropopliteal PTA. Compliance was comparable. The patients in the two groups had similar clinical and angiographic characteristics. Patency was assessed with noninvasive methods 1 day and then 3, 6, and 12 months after PTA and was confirmed at angiography at the end of the study in 112 patients.\n Patency in patients who received anticoagulants was 53% and was not statistically significantly different from 69% in patients who received ASAD (P = .18). With anticoagulants, there were four bleeding complications (one was fatal); with ASAD, only five minor complications occurred.\n ASAD is at least as effective as anticoagulants for secondary prevention of obstruction after PTA but has less severe side effects.", "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.", "To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease.", "Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long-term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events.\n Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0-3.0; n=3371) or clopidogrel (75 mg per day) plus aspirin (75-100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00243178.\n The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76; p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively).\n Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy.", "This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.\n Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.\n We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.\n Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.\n The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.", "To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice.\n Randomised controlled trial.\n 729 patients aged >/=60 years with atrial fibrillation, recruited in general practice, who had no established indication for coumarin. Mean age was 75 years and mean follow up 2. 7 years.\n Primary care in the Netherlands.\n Patients eligible for standard intensity coumarin (international normalised ratio 2.5-3.5) were randomly assigned to standard anticoagulation, very low intensity coumarin (international normalised ratio 1.1-1.6), or aspirin (150 mg/day) (stratum 1). Patients ineligible for standard anticoagulation were randomly assigned to low anticoagulation or aspirin (stratum 2).\n Stroke, systemic embolism, major haemorrhage, and vascular death.\n 108 primary events occurred (annual event rate 5.5%), including 13 major haemorrhages (0.7% a year). The hazard ratio was 0.91 (0.61 to 1.36) for low anticoagulation versus aspirin and 0.78 (0.34 to 1.81) for standard anticoagulation versus aspirin. Non-vascular death was less common in the low anticoagulation group than in the aspirin group (0.41, 0.20 to 0.82). There was no significant difference between the treatment groups in bleeding incidence. High systolic and low diastolic blood pressure and age were independent prognostic factors.\n In a general practice population (without established indications for coumarin) neither low nor standard intensity anticoagulation is better than aspirin in preventing primary outcome events. Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice." ]

[ "2030245", "17663611", "11680554", "1460157", "17076751", "7673531" ]

[ "A comparative evaluation of parent-training interventions for families of chronic delinquents.", "An adaptive approach to family intervention: linking engagement in family-centered intervention to reductions in adolescent problem behavior.", "Reducing conduct problems among children of battered women.", "Family preservation using multisystemic therapy: an effective alternative to incarcerating serious juvenile offenders.", "Randomised controlled trial of a parenting intervention in the voluntary sector for reducing child conduct problems: outcomes and mechanisms of change.", "Preventing escalation in problem behaviors with high-risk young adolescents: immediate and 1-year outcomes." ]

[ "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.", "This study used Complier Average Causal Effect analysis (CACE; see G. Imbens & D. Rubin, 1997) to examine the impact of an adaptive approach to family intervention in the public schools on rates of substance use and antisocial behavior among students ages 11-17. Students were randomly assigned to a family-centered intervention (N = 998) in 6th grade and offered a multilevel intervention that included (a) a universal classroom-based intervention, (b) the Family Check-Up (selected; T. J. Dishion & K. Kavanagh, 2003), and (c) family management treatment (indicated). All services were voluntary, and approximately 25% of the families engaged in the selected and indicated levels. Participation in the Family Check-Up was predicted by 6th-grade teacher ratings of risk, youth reports of family conflict, and the absence of biological fathers from the youths' primary home. Relative to randomized matched controls, adolescents whose parents engaged in the Family Check-Up exhibited less growth in alcohol, tobacco, and marijuana use and problem behavior during ages 11 through 17, along with decreased risk for substance use diagnoses and police records of arrests by age 18.", "This study was an experimental evaluation of an intervention designed to reduce conduct problems among children of battered women. Participants were 36 families (mothers and children) in which the mother had sought shelter because of relationship violence and had at least 1 child (4-9 years old) with clinical levels of conduct problems. The intervention consisted of 2 primary components: (a) providing instrumental and emotional support and (b) teaching child management skills to mothers. Families were randomly assigned to either the intervention condition or the existing services comparison condition and were assessed on 5 occasions over 16 months after shelter departure. Compared with families receiving existing services, children in the intervention condition improved at a faster rate, the proportion of children displaying clinical levels of conduct problems was greatly diminished, and mothers displayed greater improvements in child management skills.", "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.", "To test effectiveness of a parenting intervention, delivered in a community-based voluntary-sector organisation, for reducing conduct problems in clinically-referred children.\n Randomised controlled trial, follow-up at 6, 18 months, assessors blind to treatment status. Participants--76 children referred for conduct problems, aged 2-9, primarily low-income families, randomised to treatment vs. 6-month wait-list group. Retention was 93% at 6 months, 90% at 18 months. Interventions--Webster-Stratton Incredible Years video-based 14-week group programme, teaches cognitive-behavioural principles for managing behaviour, using a collaborative, practical, problem-solving approach. Primary outcomes--child problem behaviour by parent-report (Eyberg) and home-based direct observation; secondary outcomes--observed positive and negative parenting; parent-reported parenting skill, confidence and depression.\n Post-treatment improvements were found in child problem behaviour, by parent-report (effect size (ES) .48, p = .05) and direct observation (ES .78, p = .02); child independent play (ES .77, p = .003); observed negative (ES .74, p = .003) and positive (ES .38, p = .04) parenting; parent-reported confidence (ES .40, p = .03) and skill (ES .65, p =.01), using ANCOVA to control for baseline scores. Maternal depression did not change. Consumer satisfaction was high. At 18-month follow-up, although no randomised comparison was possible, changes appeared to maintain, with no significant change toward baseline level on any measure. Change in observed positive parenting appeared to mediate change in child problem behaviour (p < .025).\n Findings suggest that a group-based cognitive-behavioural parenting programme, delivered by well-trained and supervised staff, can be effective in a community voluntary-sector setting, for reducing conduct problems and enhancing parenting skills. Change in parenting skill appears to be a key mechanism for change in child behaviour. Findings have implications for feasibility of translating evidence-based programmes, even for clinically-referred conduct problems, into less specialised community settings, likely to have lower costs and be more accessible for families.", "The study tested alternative intervention strategies to reduce escalation in problem behaviors among high-risk young adolescents (11 to 14 years old). A total of 158 families with young adolescents (male and female) participated in this study. Of these, 119 families were randomly assigned to 1 of the following intervention conditions: (a) parent focus, (b) teen focus, (c) parent and teen focus, (d) self-directed change (materials only). In addition, 39 families of young adolescents were recruited as a quasi-experimental control. Parent focus and teen focus interventions resulted in immediate beneficial effects in observed and reported family conflict. The parent intervention conditions showed immediate beneficial effects on behavior problems at school. Longitudinal trends suggest that the parent focus condition may reduce subsequent tobacco use, compared with all other approaches. Interventions that aggregated high-risk youths into groups, however, showed the highest escalations in tobacco use and problem behavior at school, beginning at termination and persisting to follow-up. These findings are discussed with respect to the need to re-evaluate strategies that aggregate high-risk youths into intervention programs and focus more on strategies to engage parents in prevention." ]

[ "2691402", "12269458", "6365424", "7822059", "7005653", "3060308", "2403486", "6572128", "6754242", "17713339", "1890532", "12218280", "1059514", "11553111", "1756217", "6593146", "14684973", "281356", "284065", "318958", "3275147", "3895545", "6989549", "8448778", "295702", "342181", "782777", "288179", "9372795", "3476237", "6593805", "7960167", "9758424", "10826050", "8521431", "3910338", "224083", "1623700", "3284939", "3288434", "9017171", "16352884", "15914981", "12000347", "6088166", "7960166", "9829868", "6594021", "6929082", "270395", "8783533", "3476523", "1547611", "22736448", "21698991", "3471376", "170634", "11460274", "9314656", "16739545", "9429811" ]

[ "Clinical trial of a low-fluoride toothpaste for young children.", "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.", "Caries prevention using a 1.2% sodium monofluorophosphate dentifrice in an aluminium oxide trihydrate base.", "Enamel opacities and dental caries in children who used a low fluoride toothpaste between 2 and 5 years of age.", "[Cariostatic effect of Fluocaril; controlled clinical research].", "A 3-year oral health dose-response study of sodium monofluorophosphate dentifrices with and without zinc citrate: anti-caries results.", "Caries-preventive effect of fluoride dentifrices with and without anticalculus agents: a 3-year controlled clinical trial.", "Combined effects of a fluoride dentifrice and mouthrinse on the incidence of dental caries.", "Comparative unsupervised clinical trial on caries inhibition effect of monofluorophosphate and amine fluoride dentifrices after 3 years in Strasbourg, France.", "Noninvasive control of dental caries in children with active initial lesions. A randomized clinical trial.", "Effectiveness of fortnightly tooth brushing with amine fluorides in caries-prone subjects.", "A randomised controlled trial of the efficacy of supervised toothbrushing in high-caries-risk children.", "Caries preventive effect of a fluoride-containing varnish (Duraphat) after 1 year's study.", "Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year.", "[The caries-protective efficacy of 2 fluoride varnishes in a 2-year controlled clinical trial].", "Caries clinical trial of fluoride rinses in a Danish Public Child Dental Service.", "Prevalence and determinants of enamel fluorosis in Flemish schoolchildren.", "Observations on dental caries in primary teeth after frequent fluoride toplications in a program involving other preventives.", "The caries-preventive effect of amine fluorides and inorganic fluorides in a mouthrinse or dentifrice after 30 months of use.", "Effect of high-concentration ammonium and sodium fluoride rinses on dental caries in schoolchildren.", "[Reduction of dental caries after two years with a combination of mouthwashes and topical fluorides].", "Effect on caries of different fluoride prophylactic programs in preschool children. A two year clinical study.", "A 3-year clinical trial into the effect of fluoride content and toothpaste abrasivity on the caries inhibitory properties of a dentifrice.", "Dental fluorosis, dental caries and fluoride exposure among 7-year-olds.", "Effect of fluoride varnish (Duraphat) in preschool children.", "Caries-preventive effect of two concentrations of stannous fluoride mouthrinse.", "Clinical study of an amine fluoride gel and acidulated phosphate fluoride gel.", "Effect of flouride varnish (Duraphat) treatment every six months compared with weekly mouthrinses with 0.2 per cent NaF solution on dental caries.", "A three-year clinical trial of a combination of trimetaphosphate and sodium fluoride in silica toothpastes.", "Effect of fluoride containing dentifrice, mouthrinsing, and varnish on approximal dental caries in a 3-year clinical trial.", "Three-year study of the effect of fluoride varnish (Duraphat) on proximal caries progression in teenagers.", "The effect of NaF and SMFP toothpastes on three-year caries increments in adolescents.", "Fluorosis risk from early exposure to fluoride toothpaste.", "Dental caries and fluorosis prevalence study in a nonfluoridated Brazilian community: trend analysis and toothpaste association.", "Fluoride varnish versus acidulated phosphate fluoride gel: a 3-year clinical trial.", "Three-year caries increments after fluoride rinses or topical applications with a fluoride varnish.", "The relative caries-inhibiting effects of a stannous fluoride dentifrice in a silica gel base.", "Caries development after termination of a fluoride rinsing program.", "Dental caries, fluorosis, and fluoride exposure in Michigan schoolchildren.", "A 3-year clinical trial to compare efficacy of dentifrices containing 1.14% and 0.76% sodium monofluorophosphate.", "Effect of supervised use of an alum mouthrinse on dental caries incidence in caries-susceptible children: a pilot study.", "The prevalence and severity of fluorosis in children who received toothpaste containing either 440 or 1,450 ppm F from the age of 12 months in deprived and less deprived communities.", "A clinical trial of a slow-releasing fluoride device in children.", "Dental fluorosis decline after changes to supplement and toothpaste regimens.", "Caries inhibition of a dentifrice containing 0.78% sodium monofluorophosphate in a silica base.", "Results from a three-year caries clinical trial comparing NaF and SMFP fluoride formulations.", "Risk factors for enamel fluorosis in optimally fluoridated children born after the US manufacturers' decision to reduce the fluoride concentration of infant formula.", "The caries-preventive effect of a fluoride varnish in the fissures of the first permanent molar.", "Caries increment and gingival status during 2 years' use of chlorhexidine- and fluoride-containing dentifrices.", "[Caries prevention by means of a Na2FPO3-toothpaste after 7 year's application].", "A comparative study of fluoride-releasing composite resin and glass ionomer materials used as fissure sealants.", "A three-year clinical comparison of a sodium monofluorophosphate dentifrice with sodium fluoride dentifrices on dental caries in children.", "Efficacy of APF treatments without prior toothcleaning targeted to high-risk children.", "Randomized trial on fluorides and sealants for fissure caries prevention.", "Occlusal caries prevention in high and low risk schoolchildren. A clinical trial.", "Clinical cariostatic effectiveness of a NaF rinse in a low prevalence child population.", "A clinical evaluation of a sodium fluoride dentifrice.", "Comparative anti-caries effects of tablet and liquid fluorides in cleft children.", "The relationship between reported toothpaste usage in infancy and fluorosis of permanent incisors.", "Fluoride dentifrice ingestion and fluorosis of the permanent incisors.", "Risk factors associated with fluorosis in a non-fluoridated population in Norway." ]

[ "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.", "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.", "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.", "A recent clinical trial investigated the cariostatic effectiveness of a low (550 ppm) fluoride toothpaste in comparison with a standard (1050 ppm) control paste in pre-school children who were 2-years-old at the start of the 3-year trial. The present study has investigated the prevalence of enamel opacities in permanent incisor teeth and of caries in children who had taken part. As well as children from test and control groups, a third group of non-trial children were included in the sample. A total of 1,523 children were examined in schools and had photographs taken of their upper permanent incisor teeth. The latter were scored using the Thylstrup and Fejerskov (TF) index for fluorosis and the modified Developmental Defects of Enamel (DDE) index. Differences between the groups were small in real terms but using the TF index the child and tooth prevalence of opacities were significantly lower in the children who had used the test paste with a lower fluoride content; the same trend was seen in diffuse defects scored using the modified DDE index. There was no significant difference in the prevalence of caries in either primary or permanent teeth although the trend in both cases was for slightly more disease in children who had used the test paste.", "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.", "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.", "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.", "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.", "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.", "The aim of this study was to investigate whether DMFS increment can be decreased among children with active initial caries by oral hygiene and dietary counseling and by using noninvasive preventive measures. Except for mentally disabled and handicapped children attending special schools, all 11- to 12-year-olds in Pori, Finland, with at least one active initial caries lesion were invited to participate in the study and were then randomized into two groups. Children in the experimental group (n = 250) were offered an individually designed patient-centered preventive program aimed at identifying and eliminating factors that had led to the presence of active caries. The program included counseling sessions with emphasis on enhancing use of the children's own resources in everyday life. Toothbrushes, fluoride toothpaste and fluoride and xylitol lozenges were distributed to the children. They also received applications of fluoride/chlorhexidine varnish. The children in the control group (n = 247) received basic prevention offered as standard in the public dental clinics in Pori. For both groups, the average follow-up period was 3.4 years. A community level program of oral health promotion was run in Pori throughout this period. Mean DMFS increments for the experimental and control groups were 2.56 (95% CI 2.07, 3.05) and 4.60 (3.99, 5.21), respectively (p < 0.0001): prevented fraction 44.3% (30.2%, 56.4%). The results show that by using a regimen that includes multiple measures for preventing dental decay, caries increment can be significantly reduced among caries-active children living in an area where the overall level of caries experience is low.\n 2007 S. Karger AG, Basel", "The aim of this study was to assess the caries incidence and plaque accumulation in schoolchildren at caries risk, after brushing the teeth fortnightly with gels containing 0, 0.4% F, 1.25% F as amine fluoride (AmF) or the common amine fluoride toothpaste containing 0.125% F. The study was conducted double blind over an 18-month period, and after 6 months discontinuation of brushing. Only the group that brushed with the 1.25% AmF gel showed a significant decrease in caries development compared to the group that brushed with the 0.125% AmF toothpaste. During the 6-month discontinuation period, the incidence of caries increased in all groups; the differences in caries development between all groups were not significant. Plaque indices were significantly lower in the AmF-treated groups. The highest fluoride concentration in the gel reduced the development of caries to zero, probably due to increased fluoride levels in the oral milieu of caries risk children. In order to maintain a positive effect of fluoride over an extended time period, caries-prone subjects should continue an initiated fluoride programme.", "Scottish children have one of the highest levels of caries experience in Europe. Only 33% of 5-year-old children in Dundee who developed caries in their first permanent molars by 7 brushed their teeth twice a day. High-caries-risk children should benefit if they brush more often with fluoridated toothpaste. The aim of this clinical trial was to determine the reduction in 2-year caries increment that can be achieved by daily supervised toothbrushing on school-days with a toothpaste containing 1,000 ppm fluoride (as sodium monofluorophosphate) and 0.13% calcium glycerophosphate, combined with recommended daily home use, compared to a control group involving no intervention other than 6-monthly clinical examinations. Five hundred and thirty-four children, mean age 5.3, in schools in deprived areas of Tayside were recruited. Each school had two parallel classes, one randomly selected to be the brushing class and the other, the control. Local mothers were trained as toothbrushing supervisors. Children brushed on school-days and received home supplies. A single examiner undertook 6-monthly examinations recording plaque, caries (D(1) level), and used FOTI to supplement the visual caries examination. For children in the brushing classes, the 2-year mean caries increment on first permanent molars was 0.81 at D(1) and 0.21 at D(3) compared to 1.19 and 0.48 for children in the control classes (significant reductions of 32% at D(1) and 56% at D(3)). In conclusion, high-caries-risk children have been shown to have significantly less caries after participating in a supervised toothbrushing programme with a fluoridated toothpaste.\n Copyright 2002 S. Karger AG, Basel", "The caries prophylactic effect of semi-annual applications of a fluoride-containing varnish (Duraphat) was tested in 121 15-year-old children. The children were divided into a test (60 subjects). The teeth of the children in the test group were coated with fluoride varnish at the beginning of the experimental period and again 6 months later. A clinical and radiographic examination of all children was performed immediately prior to the first application of varnish and 1 year later. The mean caries increment was 0.9 new DMFS in the test group and 4.0 in the control group. The difference was statistically significant at the 0.1% level. The caries prophylactic effect on different tooth surfaces was statistically significant both on proximal and on occlusal surfaces at the 0.1% level. Analyzing the material with respect to the caries prophylactic effect against the background of caries prevalence at the start of the investigation showed a better effect in the group of children with low and medium initial DMFS values.", "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.", "The aim of this randomized, double-blind study was to measure the cariostatic effect of Bifluorid 12 (VOCO GmbH), containing 6% sodium fluoride and 6% calcium fluoride and Laweflour-Schüttellack (LAW), containing 5% sodium fluoride in comparing of placebo varnish. The caries study included 400 schoolchildren, aged 12-14 years. The tests according to the DMFS were carried out by two independent examiners. The 400 children were divided into 3 test and 1 placebo group, each group consisting of 100 subjects. After two years there was a significant inhibition of caries increment in all test groups compared to placebo group. Percentage caries reduction ranged from 25 to 30%. The highest effect was stated at proximal surfaces.", "365 2nd through 4th graders completed a 3-yr clinical trial on the caries-preventive effect of rinsings every second week during the school year with 10 ml of an 0.2% neutral solution of sodium fluoride. All children received regular dental examinations and treatment in clinics established by the municipality in which the study took place. The trial was performed under double-blind conditions. The caries increment on teeth erupted at baseline was 1.75 DMFS in the fluoride group and 1.83 DMFS in the placebo group (P greater than 0.05; 95% confidence limits for percentage caries reduction: -20.7% and 29.5%). The caries increment on teeth erupting during the trial was 0.73 DMFS in the fluoride group and 0.99 DMFS in the placebo group (P greater than 0.05; 95% confidence limits for percentage caries reduction: 1.0% and 51.6%).", "As part of an epidemiological study on the oral health of Flemish schoolchildren, fluoride use was studied together with risk factors (medical history, tap water fluoride concentration, use of fluoride supplements, toothpaste and brushing habits). Fluorosis was scored according to the Thylstrup-Fejerskov index (TFI) in children aged 11 years (4,128 children examined). Explanatory variables were recorded yearly, starting at the age of 7. Earliest toothpaste use was reported at the age of 1. By age 7, 99.7% of the children reported the use of toothpaste (90% fluoride-containing), but only 13.9% reported using a pea-sized amount. At age 7, 66% of the children had received systemic fluoride supplements during at least part of their childhood. At 11 years, 92% of the children used a fluoride-containing toothpaste and 6% still received systemic fluoride supplements. Fluorosis was present in about 10% of all the children examined, mainly TFI score 1 (7.3% in upper central incisors). Logistic regression established tooth brushing frequency and fluoride supplement use, in addition to tap water fluoride concentrations above 0.7 mg/l, as significant risk factors when the presence of fluorosis on at least one tooth was used as outcome variable. Children having fluorosis had a lower risk of caries, both in the primary (median dmft 1, range 0-10 vs. 2, range 0-12) and permanent dentition (median DMFT 0, range 0-5 vs. 0, range 0-11).\n Copyright 2004 S. Karger AG, Basel", "The anticaries effect of repeated toplications with APF gel was assessed in the primary dentition of 2-6-year-olds after 8, 18 and 28 months. Frequent, but less than daily, topical fluoride therapy appeared to have little effect in pre-school children consuming water-borne fluoride and receiving other traditionally recommended modalities of prevention.", "The study groups using a dentifrice and mouthrinse both containing fluorides, a dentifrice containing stannous fluoride and a mouthrinse containing sodium fluoride, or a mouthrinse containing sodium fluoride with a placebo dentifrice had a 20.7% to 29.0% lower DMF increment than the control group after 30 months. These differences were significant. The study groups using a dentifrice containing amine fluorides and a placebo mouthrinse, a mouthrinse containing amine fluorides and a placebo dentifrice, or a dentifrice containing stannous fluoride and a placebo mouthrinse had a 13.6% to 22.4% lower DMF increment than the control group. These differences were not statistically significant. There was no significant difference in effectiveness against caries between the use of the organic or inorganic fluoride products.", "A double-blind clinical trial was conducted in a non-fluoridated community to determine the effect on enamel fluoride and caries experience of daily rinsing in school with 1,000 parts/10(6) solutions of ammonium fluoride or sodium fluoride at pH 4.4. Subjects were 10- to 12-year-old children (n approximately equal to 200/group at baseline), about one-half of whom reported the usage of fluoride supplements. Dental caries (DFS index) and enamel fluoride (in vivo biopsy) were evaluated at baseline, 12 months, and 24 months. Supplement users had higher enamel fluoride levels and less caries experience initially, as well as generally lower caries increments over the study. In year 1, the overall caries reductions (supplement users and non-users combined) were 23 % (ammonium fluoride) and 33 % (sodium fluoride), P less than 0.01. For year 2, treatment effects were significantly greater: 54 % (ammonium fluoride) and 47 % (sodium fluoride). In newly erupted teeth, the effects of the ammonium fluoride (70 % DFS reduction) was significantly greater (P = 0.013) than that of the sodium fluoride (48 % DFS reduction). Enamel fluoride levels at the end of 2 years were 3,124 parts/10(6) (ammonium fluoride), 2,771 parts/10(6) (sodium fluoride), and 2,603 parts/10(6) (placebo), P = 0.025.", "The study's purpose was to evaluate the reduction of dental caries incidence by the association of two preventive methods. 246 students of both sexes aged from 7 to 11 years registered in \"Escola de Educação Básica da Universidade Federal de Uberlândia\" and living in the urbana area of Uberlândia, state of Minas Gerais, were examined. The sample was distributed into two groups: children from Group 1, which received a semestral topical application of Acidulated Fluor Phosphate at 1.23% and children from Group II, that besides the topical application above related (Group I) also received weekly mouthwashes of sodium fluoride aquesus solution at 0.2%. After two years of study DMFS index were tabled and statistically analysed. It was verified a reduction of 33.97% in the incidence of dental caries (in the permanent dentition). The difference between the Groups was significant at 5% level of confidence.", "376 three-year old children were divided into four experimental groups and exposed to different combinations of preventive programs for a period of two years. All the groups were given the same basic prophylactic information. Additionally Group I received fluoride tablets (FLUDENT) for daily sucking twice a day plus a placebo dentifrice free of fluoride. Group II was given a fluoride dentifrice containing 0.025% F, (ACTA). Group III was given a placebo dentifrice plus fluoride varnish (Duraphat) twice a year. Group IV a fluoride dentifrice containing 0.025% F (ACTA) plus fluoride varnish (Duraphat) twice a year. No statistically significant difference in caries increment during the two experimental years was found between the groups. A tendency to lower caries increment was found in Group IV, i.e. in the children using the low fluoride dentifrice and treated twice a year with fluoride varnish.", "The effect of reducing the abrasivity of toothpaste on dental caries was observed in a 3-year clinical trial involving 1106 11-13-year-old Berkshire schoolchildren were divided into three groups; Group 1 were allocated a low abrasivity paste containing 0.8% sodium monofluorophosphate, Group 2 a paste of conventional abrasivity also containing 0.8% sodium monofluorophosphate and Group 3 a low abrasivity non-fluoride paste. After 3 years the net DMFS increments (clinical and radiographic scores combined) were 4.22 in Group 1, 4.72 in Group 2 and 6.43 in Group 3. The differences between Groups 1 and 3 and between Groups 2 and 3 were highly significant (P less than 0.001). The mean increment in Group 1 was lower than in Group 2 but did not reach statistical significance. Reducing the abrasivity of the toothpaste had no meaningful effect on the standard of oral hygiene and prevalence of gingivitis as measured by the Gingival and Plaque Indices.", "Mild dental fluorosis is frequently linked to fluoridated water, but discretionary fluoride sources may also be important. The aim of this study was to record age of weaning and fluoride exposure from water, toothpaste and supplements, and to relate these to the presence of caries and fluorosis in children born in 1983. In Perth (Western Australia) 14 school classes were selected. The 350 children (mean age 7.5 years) ultimately included gave fluoride exposure data for the period birth to 4 years of age. Caries (DMFT, WHO criteria, no radiographs) and dental fluorosis (TF index, dry permanent incisors) were registered clinically. Most (89%) children had lived at least 2.5 years in a fluoridated area. Supplement use was minimal and unrelated to caries or fluorosis. Mean age of weaning of those who had been breast-fed was 7.7 months; by 9 months, 74% had been weaned. Eighty-five percent liked toothpaste, 60.7% had swallowed it, and the mean age of starting to use it was 1.5 (SD 0.96) years. Caries prevalence was 0.1 and mean DMFT was 0.13. The prevalence of fluorosis was 0.48; 63% of fluorosis was TF score 1. Residence in a fluoridated area for > or = 2.5 of the first 4 years of life had an odds ratio (OR) of 4.9 for fluorosis. Weaning before 9 months of age, swallowing toothpaste and liking toothpaste were also statistically significant risk factors. Major risk factors for more severe fluorosis (TF > or = 2) were early weaning and swallowing toothpaste (ORs 2.77 and 2.64, respectively). Residence in a fluoridated area (OR 2.2) was not a statistically significant risk factor.(ABSTRACT TRUNCATED AT 250 WORDS)", "The caries-preventive effect of semiannual applications of a fluoride varnish (Duraphat) was tested for 2 years in 225 3-year-old children; 113 children served as a control group. At the baseline examination, 69% of the children in the test group and 75% in the control group were caries-free. The results after 2 years showed an average caries increment of 2.1 surfaces in the test group and 3.7 in the control group. The difference is statistically significant. Thirty-eight percent of the children in the test group and 27% in the control group were still caries-free. The caries reduction was 44%.", "The effectiveness of a stannous fluoride mouthrinse, when used once each school day, was investigated in a 3-year study. Effervescent stannous fluoride tablets of two concentrations were dissolved in 20 ml of water, giving solutions of 100 parts/10(6)F- and 200 parts/10(6)F- respectively. Approximately 1,200 children, with a mean age of 10 years, were divided on a random basis into three groups. Two of the groups rinsed with the two strengths of solution and the third group rinsed with a placebo. Examinations were carried out at the commencement of the study, and at yearly intervals thereafter. The final series was carried out a year after the rinsing procedures were terminated. There were significant reductions in the numbers of new caries in each of the two experimental groups as compared with the controls. The concentration of the solutions appeared to have little influence on the results. More dramatic reductions were noted in the teeth which erupted during the course of the study. A residual effect was demonstrated a year after the rinsing procedures were terminated.", "This study compared caries inhibition in children by an amine fluoride and an acidulated phosphate fluoride when administered in a topically applied gel. In addition, the effects of applying amine fluoride daily and weekly were compared. Four hundred and sixty-eight children, ages 6 to 13, were randomly assigned to one of five treatment groups and received a total of five, 5-minute treatments. The treatment and interval between each of the five treatments were as follows:(A)acidulated phosphate fluoride daily, (B) amine fluoride daily, (C) amine fluoride weekly, (D) placebo daily, and (E) placebo weekly. When the children were examined for total Decayed, Missing, and Filled Surfaces (DMFS) increments 2 years later, no significant differences were observed. However, when the data were examined for effects of DMFS for specific tooth surface, significant restriction (61%) of occlusal increment was shown in the group which was treated with amine fluoride daily for 5 consecutive days as compared with the control group.", "Recent studies have shown a high fluorine uptake in the enamel and a considerable caries reduction following the application of varnished containing fluoride. As the application is easy to carry out it may in certain situations serve as an alternative to other topical fluoride school programmes. The aim of the present study, therefore, was to compare the caries increment in schoolchildren exposed to a fluoride varnish (Duraphat) every six months and in children receiving the conventional weekly fluoride mouthrinsing programme with 0.2 per cent sodium fluoride over a two-year period. Two hundred 14-year-old children, divided into one test and one control group took part in the study. They were clinically and radiographically examined every year. Preexperimental data revealed no differences between the groups. During the experimental period the children in the fluoride varnish group developed a statistically significant lower number of new carious lesions compared with those in the mouthrinsing group. The difference in caries increment was about 30 per cent. Further clinical studies to compare the effects of various topical fluoride programmes are recommended.", "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.", "The purpose of this study was to evaluate the separate effect of fluoride dentifrice, fluoride mouthrinsing and fluoride varnish on approximal dental caries. All 252 13-14-yr-old children at an elementary school were selected at random and divided among four groups for a 3-yr longitudinal study. Group 1 received a fluoride dentifrice for home care and a fluoride mouthrinse once a week. Group 2 received a fluoride dentifrice for home care and a placebo mouthrinse once a week. Group 3 received a fluoride dentifrice for home care and a fluoride varnish once every 3 months. Group 4 received a placebo dentifrice for home care and a fluoride rinse once a week. Fluoride rinsing did not give any additional effect compared with placebo-rinsing when a fluoride dentifrice was used for home care. Fluoride varnish gave a significant caries reduction compared with fluoride rinsing.", "The effect of sodium fluoride varnish (Duraphat) applications on proximal caries progression was studied during a 3-yr period in 87 teenagers and compared to a control group (n = 107). In the fluoride varnish group the children were treated with fluoride varnish every third month during the experimental period. Caries lesions on the mesial surfaces of first premolars to the mesial surfaces of second molars were recorded annually on radiographs and an individual progression value was calculated. The study showed that topical application of fluoride varnish every third month significantly (P less than 0.05) reduced the progression of proximal caries lesions in premolars and molars. The most obvious reduction of caries progression was observed among children who developed between two and eight new proximal lesions during the test period. In the children with the highest caries activity (greater than nine new proximal lesions) Duraphat treatments did not significantly reduce proximal caries progression in premolars and molars.", "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)", "Swallowed fluoride toothpaste in the early years of life has been postulated to be a risk factor for fluorosis, but the epidemiological evidence is weakened by the fact that most of the relevant studies were done in developed countries where an individual is exposed to multiple sources of fluoride.\n To quantify the risk of fluorosis from fluoride toothpaste in a population whose only potential source of fluoride was fluoride toothpaste.\n Case-control analyses were conducted to test the hypothesis that fluoride toothpaste use before the age of 6 years increased an individual's risk of fluorosis. Data came from a cross-sectional clinical dental examination of schoolchildren and a self-administered questionnaire to their parents. The study was conducted in Goa, India. The study group consisted of 1189 seventh grade children with a mean age of 12.2 years.\n The prevalence of fluorosis was 12.9% using the TF index. Results of the crude, stratified, and logistic regression analyses showed that use of fluoride toothpaste before the age of 6 years was a risk indicator for fluorosis (OR 1.83, 95% CI 1.05-3.15). Among children with fluorosis, beginning brushing before the age of 2 years increased the severity of fluorosis significantly (P<0.001). Other factors associated with the use of fluoride toothpaste, such as eating or swallowing fluoride toothpaste and higher frequency of use, did not show a statistically significant increased risk for prevalence or severity of fluorosis.\n Fluoride toothpaste use before the age of 6 years is a risk indicator for fluorosis in this study population.", "The main purpose of this study is to compare data from previous surveys to current prevalence rates of dental caries and dental fluorosis in eleven- and twelve-year-olds in a non-fluoridated Brazilian community (< 0.2 ppm F). This study also assesses the possible association between use of fluoride toothpaste and the prevalence of dental caries and dental fluorosis. The sample subjects are randomly selected schoolchildren who were examined with a dental probe and buccal mirror under natural light. The intra-examiner error was calculated, using Kappa statistics (K tau 0.85). The results showed that between 1991 and 1997 there was a 56.7 percent decrease in the prevalence of dental caries and an 80.1 percent increase in dental fluorosis. Children with dental fluorosis were 1.75 times more likely to be free of caries (OR = 1.75-CI:0.43, 6.68). Children who started using fluoride toothpaste before the age of three were 4.43 times more likely to have dental fluorosis than those who started using it after the age of three (OR = 4.43-CI:0.51, 99.61). The results of the cross-sectional surveys conducted with schoolchildren in 1991, 1995, and 1997 suggest a continuing decrease in the prevalence of dental caries and an increase in the prevalence of dental fluorosis in this nonfluoridated Brazilian town.", "The aim of this trial was to compare the caries-preventive effect of sodium fluoride varnish and acidulated phosphate fluoride (APF) gel. A total of 254 children aged 12-13 years with high past caries experience were randomly divided into two groups. The participants received semi-annual applications of either fluoride varnish or APF gel for 3 years. During the study, the mean (+/- SD) total DMFS increments of the varnish and gel groups were 6.8 +/- 5.6 and 7.7 +/- 6.4, respectively, when initial caries was included, and 3.1 +/- 3.7 and 3.6 +/- 4.6 when initial caries was excluded. The difference was most evident on the approximal surfaces (varnish: 1.4 +/- 2.4; gel: 1.9 +/- 3.1). However, this difference was not statistically significant. Although larger studies are needed for firm conclusions about the comparative effect of the two fluoride measures, the results suggest that fluoride varnish is as effective as fluoride gel at least in preventing approximal caries. Taking into account the shorter treatment time, using fluoride varnish for professional applications seems justified.", "251 9-12-yr-old children completed a 3-yr, double-blind, clinical trial of two caries preventive fluoride programs. Caries increments and progression patterns were compared in two groups of children who rinsed every fortnight with a 0.2% NaF solution or received biannual topical applications with a fluoride varnish (Fluor-Protector). Clinically recorded mean DFS increments were 3.3 +/- 0.2 (SE) in the rinse group and 3.5 +/- 0.2 in the varnish group. In both groups nearly half of these increments were recorded in the occlusal surfaces of second molars. The mean incremental DFS recorded radiographically on approximal surfaces of posterior teeth were 1.1 +/- 0.2 and 1.5 +/- 0.2 in the rinse and varnish group, respectively. None of the inter-group differences were statistically significant (P greater than 0.05). Detailed analyses of the radiographic scores revealed a similar and extremely slow caries progression in the two study groups and they strengthened the conclusion of equal clinical efficacy of the two treatments. None of the fluoride programs had been able to change preestablished patterns of caries development among the children.", "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.", "In a municipality near Copenhagen, Denmark, where fortnightly fluoride rinses with 0.2% neutral sodium fluoride had been performed for more than a decade, 1306 children from kindergarten through 6th grade were stratified by school and grade and randomly distributed into two groups. One group continued the fluoride rinses, the other group had the fluoride solution replaced with distilled water. Both solutions were slightly flavored. 1083 children completed the 3-yr trial. Caries was recorded clinically by the dentists in the municipal dental service using the diagnostic criteria for the Child Dental Health Services, and on bitewing radiographs by one of the authors applying the criteria developed by GRONDAHL et al. Permanent molars and premolars were included in the study. Clinically, caries increment in the two groups was the same with pits and fissures containing 94% of the DMFS. According to the radiographs, caries progression in the water group was higher than in the fluoride group. This difference was statistically significant for the surfaces erupting during the study (P less than 0.05).", "This study relates the prevalence of caries and fluorosis among Michigan children, residing in four different areas, to the various concentrations of F in the communities' water supplies. Demographic information, details of F history, and dental attendance data were collected by a questionnaire form filled out by parents. Children ages six to 12 were screened for caries by means of the NIDR criteria and for fluorosis by means of the TSIF index. Results pertain only to continuous residents and the permanent dentition. The prevalence of both caries and fluorosis was significantly associated with the F concentration in the community water supply. Approximately 65% of all children were caries-free, ranging from 55.1% in fluoride-deficient Cadillac to 73.7% in Redford (1.0 ppm F). About 36% of all children had dental fluorosis, ranging from 12.2 in Cadillac to 51.2 in Richmond (1.2 ppm). All of the fluorosis was very mild. From logistic regression, the prevalence of caries was significantly associated with age, dental attendance, and the use of a water supply fluoridated at 1.0 ppm. The odds of experiencing fluorosis increased at every F level above the baseline (Cadillac), with the use of topical F rinses, and with age. Results suggest that children in the four communities may be ingesting a similar level of F from sources such as dentifrices, dietary supplements, and professional applications, but the factor that differentiates them with respect to the prevalence of caries and fluorosis is the F concentration in the community water supply.", "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.", "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.", "This study compared fluorosis in the upper central incisors of children from socially diverse backgrounds who had received either 440- or 1,450-ppm F toothpaste from 12 months of age. The children were resident in non-fluoridated districts in the north-west of England. They received either 440- or 1,450-ppm F toothpaste and advice regarding its use until the age of 5-6 years. Dental fluorosis (TF index) was assessed on digital images of dried teeth when the children (n = 1,268) were 8-10 years old. In the less deprived districts the prevalences of fluorosis (TF >or=0) for the 1,450- and 440-ppm F groups were 34.5 and 23.7% (p = 0.006). In the deprived districts the prevalences of fluorosis were 25.2 and 19.5% (p = 0.2). Overall the prevalences of TF >or=2 were 7 and 2.1% for the 1,450- and 440-ppm F groups and 2.2 and 0.2% for TF >or=3. These differences were statistically significant (p < 0.003). There was a strong association between the deprivation status of wards and fluorosis. Only 1 subject with a TF score of 3 was identified in the two most deprived quintiles of the Townsend score. It is concluded that careful targeting of programmes of this type to children living in high caries risk deprived communities carries only a small risk of aesthetically objectionable fluorosis (TF >2) whether low or high fluoride toothpastes are used. High fluoride (1,450 ppm F) toothpastes should not be provided on a community basis to very young children in less deprived communities.", "The objective was to test a fluoride-containing slow-release device in preventing dental caries in children. Accordingly a population of 174 children aged 8 years living in a high-caries, low socio-economic area of Leeds (UK) was assembled. Two slow-release/dissolving glass (SFG) pellets, one with fluoride (F) and one without, were randomly attached to the maxillary molars of the children. Baseline caries as dmft/s, DMFT/S, periodontal disease, plaque and calculus were recorded using standard indices. Unstimulated saliva samples were collected 2 h postprandial for F analysis. All parameters were measured at 6-month intervals for 2 years. There were 132 children completing the trial of whom 63 (test n = 31, control n = 32) still retained the glass devices at the end. Comparison of mean values for gingival health and calculus showed no differences between groups throughout the trial. Mean caries as dmfs at the end of the trial (2.26) was significantly lower for the test (SFG, 2.26) compared with that for the control children (8.41; p < or = 0.001). DMFS was significantly lower at 0.84 and 2.34, respectively (p < or = 0.05). Mean salivary fluoride concentrations were 0.11 and 0.03 mg/l for test and control groups. It was concluded that placement of a glass slow-releasing fluoride device significantly reduced caries incidence in a group of low socio-economic schoolchildren over 2 years.\n Copyright (c) 2005 S. Karger AG, Basel.", "In 1989/90, in 659 12-year-olds in Perth (F 0.8 mg/L) and the Bunbury region of Western Australia (WA) (F approximately 0.25 mg/L), dental fluorosis prevalences were 40.2% and 33.0%. Fluoride supplements (OR 4.63) and extended residence in a fluoridated area (OR 4.06) were significant risk factors; toothpaste ingestion variables had ORs greater than unity; in 1990, DMFT for this age group was 0.84. School Dental Service took steps to discourage supplement and toothpaste ingestion and to promote low fluoride toothpaste for children < 6 years of age.\n To evaluate the effect of this campaign on fluorosis and caries.\n Between May-July 2000, 582 10-year-olds were examined for dental fluorosis (TF index) and dental caries (DMFT) in school dental clinics.\n Fluorosis prevalence was 22.2% in Perth and 10.8% in the Bunbury region. Overall prevalence was 18.0% and of this, 80.2% was TF 1, 17.9% was TF 2 and just 1.9% was TF 3. In 1989/90, 79 children had used supplements before the age of 4 year; in 2000 only 40 had done so (P < 0.001). Mean DMFT values in Perth and Bunbury were 0.32 and 0.28 (P > 0.05). Low F toothpaste, unavailable in 1989/90, had been used by 24.5%. The only significant risk factor was residence, OR 2.0.\n Fluorosis prevalence seems to have fallen in parallel with a reduction in discretionary intake from supplements and toothpaste. No increase in dental caries experience was recorded. Because the teeth examined in this study were at risk of fluorosis in 1992-95, very soon after policies changed, and because people are slow to change health habits, it seems reasonable to expect a further improvement when teeth mineralised in the late 1990s become visible.", "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.", "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).", "This case-control study investigated risk factors for enamel fluorosis in optimally fluoridated children, born after the US infant formula industry voluntarily reduced the fluoride content of their products. Analysis was performed on 233 children, aged 10-14 years. Case-control status was determined using the Fluorosis Risk Index (FRI). Risk factor exposure was ascertained via a mailed questionnaire. Logistic regression analyses revealed a strong association between mild-to-moderate enamel fluorosis on early forming (FRI classification I) enamel surfaces and both fluoride supplement use (odds ratio (OR)=5.95, 95% confidence interval (CI) 1.06-33.53), and early fluoride toothpaste use (OR=6.35, 95% CI 1.21-33.40). The authors found a suggestive, but nonsignificant, association between fluorosis on these enamel surfaces and infant formula in the form of powdered concentrate (OR=4.33, 95% CI 0.73-25.66). There was a strong association between mild-to-moderate fluorosis on later forming (FRI classification II) enamel surfaces and infant formula use in the form of powdered concentrate (OR=10.77, 95% CI 1.89-61.25), fluoride supplement use (OR=10.83, 95% CI 1.90-61.55), and early fluoride toothpaste use (OR=8.37, 95% CI 1.68-41.72). No association was observed between the use of ready to feed infant formula and enamel fluorosis.", "The aim of the present study was to assess the caries-preventive effect of topical application of Duraphat on the occlusal surface of newly erupted first permanent molars. A base-line examination was performed on children aged 5 years and 9 months. The children were randomly divided into a Duraphat group and a control group. In accordance with the anatomy of the fissure system, the molars were divided into shallow and deep fissures, respectively. From the time of eruption, 381 molars were examined every 3rd month during 24 months. Duraphat was applied every 6th month, altogether four times. The results showed that in the Duraphat group 35% of the fissures were decayed compared with 80% in the control group. Caries reduction amounted to 56%, and the caries-preventive effect was found in molars with shallow and deep fissures.", "A total of 91 schoolchildren, 13 years of age, were distributed into three groups. Three test dentifrices were used containing 0.1% NaF, 0.1% NaF and 2% chlorhexidine, and 2% chlorhexidine, respectively. The caries increment and gingival conditions over a period of 2 years were recorded. The caries data of the groups were compared and related to two reference groups in order to estimate a possible influence upon the study results by a change in caries incidence general to the area and age groups in question. There was less caries in the group using the dentifrice containing fluoride and chlorhexidine than in the two other test groups. The differences in caries increment between the groups were not statistically significant. The gingival health seemed to improve in all groups, but there were no statistically significant differences between the groups. The caries data from the reference groups indicated that the general trend towards reduced caries incidence was different from that of the study group.", "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%.", "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.", "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.", "A clinical field trial was conducted, over a 2-yr period, to evaluate the efficacy of bi-annual APF gel topical applications without previous prophylaxis in reducing dental caries among high-risk children living in non-fluoridated communities. 488 children 6 yr old, presenting at least three cavities on proximal surfaces of their primary teeth, were randomly assigned to two groups. The experimental group received bi-annual topical APF gel applications and the control group received a placebo. All treatments were given at school without any prior toothcleaning. The APF gel provided a 34.3% reduction in caries incidence (P-value = 0.03) among the children with 3-14 cavities on their primary teeth at the beginning of the study. However, the treatment did not show any efficacy in reducing caries incidence among the higher-risk children having initially more than 14 cavities. These findings suggest that the efficacy of APF gel applications without previous prophylaxis varies according to the individual risk of the subjects and that more comprehensive programs should be targeted to very high-risk children.", "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).", "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.", "Epidemiologic studies in which oral health in schoolchildren in the nonfluoridated city of The Hague has been monitored, have revealed a substantial decrease in caries prevalence since 1969 in groups of all socioeconomic status (SES). Because of a still significantly higher caries activity in children of lower socioeconomic classes, in 1981 a weekly fluoride mouthrinsing program in these children was started. The purpose of the present study was to investigate the cariostatic effectiveness of a weekly 0.2% neutral NaF rinse in children with low caries prevalence. A sample of 29 schools stratified according to SES and randomly assigned to two groups was selected. One group of schools (14) performed weekly rinsing and the other group (15) served as controls. After 3 yr the number of children available for re-examination had dropped from 501 to 333, of which 62.2% had written parental consent for radiographic examination. Statistical analysis of the data showed that fluoride rinsing could establish a reduction in caries incidence only in children who did not use fluoride tablets. The results of this study are of special interest for health authorities in planning and implementing public dental health measures.", "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.", "Children with cleft lip and/or palate are at a higher risk for developing caries of the primary incisors compared with non-cleft children. To determine whether fluoride in tablet or liquid form would be more efficacious with children with cleft lip and/or palate, a two-year clinical investigation was conducted to test the anti-caries effects. One-hundred and fifteen cleft children (59 boys and 56 girls) between 22 and 26 months old were randomly selected into control, tablet and liquid fluoride groups. The amount of administered fluoride was 0.25 mg F daily in non-fluoridated Taiwan. Dental examinations were conducted using mirrors and #23 explorers. Caries were assessed using the DMF index in the baseline, first year and second year. The results showed that children in the tablet and liquid groups had a significantly lower DMFT increment than in the control group (p < 0.05). In the DMFS index, children in the liquid group showed a significantly lower caries increment than in the control group (p < 0.01), and children in the tablet group presented a borderline, but non-significant statistical difference when compared with the control group (p = 0.065). No significant statistical difference was found in either DMFT or DMFS between tablet and liquid fluoride administrations (p = 0.521 and p = 0.383, respectively). It is concluded that dietary fluoride supplements in liquid form show efficacy in reducing early childhood caries in the cleft children. Liquid fluoride showed slightly better numerical anti-caries effect than tablet fluoride, which is possibly due to its ease of administration with small children.", "To examine a possible relationship between reported toothbrushing habits in infancy and fluorosis of permanent maxillary incisors at age 8-9 years.\n Comparison of clinical findings with retrospective survey data.\n Five primary schools in the City of Birmingham where the water is fluoridated at 1.0 mg F/l.\n Results of clinical examinations were compared with historical data collected via parental questionnaires. Maxillary central incisors of 325 consecutive children were examined for fluorosis clinically and photographically according to the criteria of the Modified Thylstrup and Fejerskov Index. 112 children had fluorosis and 213 did not. Information concerning toothbrushing habits in infancy was obtained via a questionnaire to parents who were also asked to add paste to a brush in a similar way to when the children were small. From a combination of questionnaire replies and paste weights the amount of fluoride that each child may have ingested from toothpaste each day was then estimated.\n Highly significant associations were found between estimated fluoride ingestion from toothpaste and fluorosis. The mean DMF score of the fluorosis group was half that of the fluorosis-free children. The prevalence of fluorosis among children in ACORN group A-C was significantly greater than in groups D-F.\n The results of the study suggest that toothpaste swallowing may be a factor in the production of fluorosis.", "Fluoride dentifrice is a primary means of preventing childhood caries, but it is also an important risk factor for fluorosis. The authors examine the influence of fluoride dentifrice ingestion on fluorosis of the permanent incisors.\n Participants in the Iowa Fluoride Study received questionnaires at regular intervals concerning fluoride sources. The authors assessed fluorosis using the fluorosis risk index. They estimated daily fluoride ingestion from dentifrice, diet and fluoride supplements and divided the amount by kilograms of body weight. The statistical analysis related fluoride ingestion to fluorosis in the permanent incisors.\n In bivariate analyses, mild fluorosis was significantly related to ingestion of fluoride dentifrice at ages 24 and 36 months (P = .02 for both). After the authors adjusted for fluoride ingested from dietary sources, logistic regression showed a significant association between fluorosis and dentifrice ingestion at age 24 months (P = .04).\n The study results suggest that fluorosis of the permanent incisors is influenced by ingestion of fluoride dentifrice during the first three years of life. Further research is needed to assess total intake of fluoride as a risk factor for fluorosis.\n These results support recommendations that young children use only a pea-sized amount of dentifrice. Parents should supervise young children as they brush their teeth with fluoride dentifrice.", "In Norway, there is no water fluoridation and little naturally occurring fluoride in drinking water. Fluoride toothpaste is used by 95% of the population and there is a long tradition of fluoride supplement use. The purpose of this study was to record the prevalence and severity of dental fluorosis in 8-year-old children and relate this to systemic fluoride exposure (supplements and toothpaste). All children (n = 551, born 1988) in a municipality in Norway were invited to participate. Dental fluorosis on the buccal surface of the upper permanent incisors was recorded according to the Thylstrup-Fejerskov index (TF). Parents provided data on use of supplements and toothpaste. Complete data were obtained from 383 children. Sixty-seven percent of the children had used fluoride supplements regularly during childhood. At 8 months or earlier, the teeth of 26% of the children, and at age 14 months or earlier the teeth of 82%, were being brushed. Among children who used fluoride supplements regularly, periodically, seldom and not at all, 45%, 21%, 10% and 0%, respectively, had dental fluorosis. The dental fluorosis was mild (TF = 1) in 87% of the cases. Bivariate and multivariate analyses showed that, in addition to use of fluoride supplements, starting toothbrushing at an early age was associated with higher prevalence of dental fluorosis. The child's birth weight and liking for or swallowing of toothpaste did not influence the prevalence of fluorosis. Risk factors for fluorosis were use of toothpaste before the age of 14 months and regular use of fluoride supplements during childhood." ]

[ "18341378", "12789464" ]

[ "Limited cytoprotective effects of amifostine in high-dose radioactive iodine 131-treated well-differentiated thyroid cancer patients: analysis of quantitative salivary scan.", "Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection?" ]

[ "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.", "Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer.\n 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m(2) carboplatin, day 1-5 in week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation.\n 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis.\n According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary." ]

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

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

[ "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.", "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.", "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." ]

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

[ "A randomized study comparing retroperitoneal drainage with no drainage after lymphadenectomy in gynecologic malignancies.", "A prospective randomized study comparing retroperitoneal drainage with no drainage and no peritonization following radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer.", "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 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.", "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.", "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." ]

[ "14505443", "18454611" ]

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

[ "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.", "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." ]

[ "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." ]

[ "19457937", "17290061", "17822748" ]

[ "Randomized multicenter phase II trial of cisplatin and ifosfamide with or without paclitaxel in recurrent or metastatic carcinoma of the uterine cervix: a Hellenic Cooperative Oncology Group (HeCOG) study.", "Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study.", "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." ]

[ "We undertook a randomized phase II trial to test whether the addition of paclitaxel (Taxol) to the cisplatin and ifosfamide (IP) combination could improve objective response (OR) rate, progression-free survival (PFS) and overall survival (OS) in patients with recurrent or metastatic cancer of the uterine cervix.\n One hundred and fifty-three patients were randomly allocated to receive either the IP regimen (ifosfamide 1.5 g/m(2), daily, on days 1-3 and cisplatin 70 mg/m(2) on day 2) or the same combination with the addition of paclitaxel 175 mg/m(2) on day 1 [ifosfamide, paclitaxel and cisplatinum (ITP) regimen]. Cycles were administered every 4 weeks on an outpatient basis.\n A modest increase in neurotoxicity was observed with the triplet combination. OR rate was significantly higher in the ITP group (59% versus 33%, P = 0.002). Median PFS was 7.9 and 6.3 months for patients in the ITP and IP arms, respectively (P = 0.023). Median OS was 15.4 months and 13.2 months in the ITP and IP arms, respectively (P = 0.048). In multivariate analysis, the triplet yielded a hazard ratio of 0.70 for relapse or progression (P = 0.046) and 0.75 for death (P = 0.124) compared with the doublet.\n The ITP combination merits further investigation in randomized phase III studies.", "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.", "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." ]

[ "15760929" ]

[ "A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs." ]

[ "In rheumatoid arthritis (RA), intramuscular (IM) pulsed depomedrone expedites an immediate response to disease modifying antirheumatic drugs (DMARDs). Although IM depomedrone is also widely used to treat disease flares in patients treated with DMARDs, its effect on radiological progression has not been assessed.\n To evaluate the benefits of 120 mg IM depomedrone versus placebo in patients with established RA whose disease was inadequately controlled by existing DMARDs.\n In a 2 year prospective randomised controlled trial patients were assessed using the ILAR/WHO core dataset, disease activity score (DAS28), x ray examination of hands and feet scored by Larsen's method, and bone densitometry.\n 291 patients with RA were screened, 166 were eligible, and 91 consented and were randomised. Disease activity improved more rapidly in the steroid treated patients than with placebo, but after 6 months no difference remained. A small but significant reduction in erosive damage in the steroid group compared with placebo was also found. More adverse reactions occurred in the steroid treated group than in the placebo patients (55 v 42), especially those reactions traditionally related to steroids (16 v 2), including vertebral fracture, diabetes, and myocardial infarction. Hip bone density fell significantly in steroid treated but not placebo patients.\n IM depomedrone improved disease activity in the short term and produced a small reduction in bone erosion at the cost of a significant increase in adverse events. Despite the initial benefit of IM depomedrone, when patients respond suboptimally to a DMARD they should not be given long term additional steroids but should be treated with alternative or additional DMARDs." ]

[ "21387176", "21888842", "17931895" ]

[ "The clinical benefit of medial support screws in locking plating of proximal humerus fractures: a prospective randomized study.", "[Surgical treatment for proximal humerus fracture].", "Primary hemiarthroplasty in four-part fractures of the proximal humerus: randomized trial of two different implant systems." ]

[ "The purpose of this study was to evaluate the clinical benefit of medial support screws for locking plating of proximal humerus fractures.\n Seventy-two consecutive patients underwent prospective treatment for proximal humerus fractures with locking plates between October 2007 and September 2008. Sixty-eight patients accomplished a mean 30.8-month follow-up and were randomized into two groups: 39 patients were treated with only a locking plate and were classified in the -MSS (medial support screw) group, and 29 patients were included in the + MSS group, which were fixed with additional medial support screws. Clinical and radiological investigations were performed in both groups.\n The fractures united at an average of 13.6 weeks after final surgery. Comparably better shoulder function recovery was achieved in the +MSS group with regard to the Constant shoulder score (P = 0.01), with the respective excellent and good rates of 79% and 62%. Eleven patients developed various complications. A statistical difference (P = 0.036) was observed regarding the failure rate (23.1% in the -MSS group vs. 3.4% in the +MSS group). The early loss of fixation was related to higher age (P < 0.001) and less initial neck-shaft angle (NSA) (P = 0.011) of the patients. However, bone mineral density was not significantly associated with loss of fixation (P = 0.076). Although no difference was found in all types of the fractures between the +MSS and -MSS groups regarding immediate postoperative NSA, we observed a significantly lower final NSA in the -MSS group and greater secondary angle loss in the subgroup of Neer three-part (P = 0.033 and 0.015, respectively) and four-part fractures (P = 0.043 and 0.027).\n Anatomical reduction can substantially decrease the risk of postoperative failure in locking plating of proximal humerus fractures. Medial support for proximal humerus fractures seems to have no benefits in Neer two-part fractures. However, the additional medial support screws inserted into the medio-inferior region of the humeral head may help to enhance mechanical stability in complex fractures and allow for better maintenance of reduction.", "The aim of the study was to compare the medical aspects of alternative surgical methods for treatment of proximal humerus fractures in specific indications (two- and three- fragment fractures).\n A prospective randomised study on surgical treatment of two- and three-fragment fractures of the proximal humerus was carried out at the Department of Surgery, University Hospital in Hradec Králové, from January 2006 till January 2010. The study comprised patients with proximal humerus fractures indicated for surgical treatment. Study inclusion criteria were as follows: informed consent, AO fracture types A2, A3, B1 or C1, age between 18 and 80 years, and patient compliance. Exclusion criteria included open fracture, associated injury (AIS . 2), open growth plates, or such state of the patient's health that would limit the extent of surgery. Two groups were compared. One included patients treated by the Zifko method of minimally invasive osteosynthesis with intramedullary K-wire insertion (MIO group) and the other (ORIF group) consisted of patients undergoing open reduction with angle-stable osteosynthesis using a Philos plate (Synthes, Switzerland). The patients were randomised to the groups by a computer programme which facilitates the maintenance of homogeneity of the groups compared. The procedure in each patient was based on the sealed-envelope method.\n The ORIF group comprised 28 patients. It took them an average of 27.2 weeks (9-72) to regain normal upper limb function. The final CM score was 86.6% (64-100%) as compared with the healthy limb. Excellent and good results were achieved in 89% of the patients; complications were recorded in 39% of them. The MIO group included 27 patients. The fractures healed in all of them. Normal upper limb function was regained at an average of 21.4 weeks (13-36). The final CM score was 87.5% (52-100%) in comparison with the healthy limb. Excellent and good results were achieved in 89% and complications developed in 33% of the patients.\n The statistical evaluation of the results, using the unpaired t-test, did not show any significant differences either in functional outcomes or the number of complications between the two groups. The only significant difference was found in operative times (117 min and 72 min in ORIF and MIO groups, respectively). The difference in time needed to regain limb function (27 and 21 weeks) was at a marginal level of statistical significance. With both methods 89% of excellent and good results were achieved, and a similar number of patients had complications (11 and 9).", "The objective of this study was to determine the effect of different prosthetic systems on the functional and radiographic outcomes after shoulder arthroplasty for fractures. This study comprised 35 patients (28 women and 7 men) with a mean age of 74 years (range, 56-88 years) who sustained 4-part fractures of the proximal humerus and were randomly allocated to 2 different groups regarding the type of prosthesis. The 2 systems used differ mainly in the type of fixation of the tuberosities. In group 1 (EPOCA), the fixation was achieved with wire cables through a medial and a lateral hole in the stem, whereas in group 2 (HAS), the fixation was performed by use of transosseous braided sutures. After a follow-up of 1 year, the functional and radiographic outcomes were evaluated. The retrieved data demonstrate that rigid fixation and anatomic positioning of the tuberosities (group 1) increase the rate of bony healing superior to all other factors. There was a statistically significant difference regarding the relative individual Constant score (P = .001) and the mean active range of motion (flexion, P < .001; abduction, P = .001; external rotation in adduction, P = .01; and external rotation in 90 degrees abduction, P = .001) when both groups were compared, showing a better outcome in the EPOCA group for all parameters. Radiologic findings, like heterotopic ossification, glenoid erosion, or subluxation, had no significant influence on the outcome in this study. Accurate placement of the tuberosities and healing at the bone-bone interface of the rotator cuff seem to be the most important factors influencing the outcome in prosthetic care of fractures." ]

[ "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", "6811710", "16330203", "6403808", "17324657" ]

[ "A prospective randomized clinical trial of total parenteral nutrition in children with cancer.", "Comparison of morbidity in children requiring abdominal radiation and chemotherapy, with and without total parenteral nutrition.", "Parenteral nutrition is not superior to replacement fluid therapy for the supportive treatment of chemotherapy induced oral mucositis in children.", "Effect of total parenteral nutrition on marrow recovery during induction therapy for acute nonlymphocytic leukemia in childhood.", "Nutrition support using the American Dietetic Association medical nutrition therapy protocol for radiation oncology patients improves dietary intake compared with standard practice." ]

[ "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.", "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.", "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.", "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.", "A randomized controlled trial previously conducted in radiation oncology patients demonstrated that nutrition intervention had a beneficial impact on body weight, nutritional status, and quality of life compared with standard practice, but it did not report on dietary intake data.\n To determine the impact of nutrition intervention compared with standard practice on dietary intake in outpatients receiving radiotherapy.\n Prospective, randomized, controlled trial.\n Sixty consecutive radiation oncology outpatients (51 men and nine women; age 61.9+/-14 years [mean+/-standard deviation]).\n Australian private radiotherapy facility.\n Patients were randomly assigned to receive either nutrition intervention (n=29) (nutrition counseling following the American Dietetic Association [ADA] medical nutrition therapy [MNT] protocol for radiation oncology) or standard practice (n=31) (general nutrition talk and booklet).\n Dietary intake (protein, energy, fiber) assessed at baseline and at 4, 8, and 12 weeks after starting radiotherapy.\n Repeated-measures analysis of variance done on an intention to treat basis.\n The nutrition intervention group had a higher mean total energy (P=0.029) and protein intake (P<0.001) compared with the standard practice group. Mean intake per kilogram of body weight for the nutrition intervention group ranged from 28 to 31 kcal/kg/day compared with 25 to 29 kcal/kg/day for the standard practice group (P=0.022). The nutrition intervention group had a higher mean protein intake (1.1 to 1.3 g/kg/day) compared with the standard practice group (1.0 to 1.1 g/kg/day) (P=0.001). Although the change in fiber intake between the groups was not significant, there was a trend in the anticipated direction (P=0.083).\n Intensive nutrition intervention following the ADA MNT protocol results in improved dietary intake compared with standard practice and seems to beneficially impact nutrition-related outcomes previously observed in oncology outpatients receiving radiotherapy. The ADA MNT protocol for radiation oncology is a useful guide to the level of nutrition support required." ]

[ "12006305", "10918757", "2258521", "8455920", "12052998", "8248962", "9506598", "12161876", "9133884", "10926959", "9832763", "16313377", "20130401" ]

[ "Does an integrated care pathway improve processes of care in stroke rehabilitation? A randomized controlled trial.", "The development of a stroke clinical pathway: an experience in a medium-sized community hospital.", "The effect of systematic care planning after acute stroke in general hospital medical wards.", "The critical path method in stroke rehabilitation: lessons from an experiment in cost containment and outcome improvement.", "Integrated care pathways and quality of life on a stroke rehabilitation unit.", "A model for management of patients with stroke during the acute phase. Outcome and economic implications.", "A randomized controlled trial of rehabilitation at home after stroke in southwest Stockholm.", "Variance analysis applied to a stroke pathway: how this can improve efficiency of healthcare delivery.", "Evaluation of a stroke family care worker: results of a randomised controlled trial.", "Randomized controlled trial of integrated (managed) care pathway for stroke rehabilitation.", "Acute stroke patients comparing outcomes with and without case management.", "Expanding the role of the stroke nurse: a pragmatic clinical trial.", "Very early rehabilitation or intensive telemetry after stroke: a pilot randomised trial." ]

[ "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.", "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.", "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.", "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.", "Integrated care pathways (ICP) may not reduce disability, institutionalization, or duration of hospitalization compared with conventional multidisciplinary team (MDT) care in organized stroke rehabilitation. Their potential to improve patient heath status or satisfaction with care is not known.\n A comparison of quality of life, caregiver strain, and patient/caregiver satisfaction at 6 months after stroke was undertaken in 152 stroke patients randomized to receive ICP or MDT care. Differences in processes of care were recorded with the use of a predefined schedule. Multivariate analyses were undertaken to identify the effect of age, sex, stroke severity, functional status, mood, and use of care pathway on quality of life score.\n The 2 groups were comparable for baseline characteristics of age, sex, stroke severity, and initial disability. MDT care was characterized by greater emphasis on return of higher function and caregiver needs compared with ICP. EuroQol Visual Analogue Scale (EQ-VAS) scores were higher in the MDT group (median, 72 versus 63; P<0.005), who also had higher scores for EuroQol dimension of social functioning (P=0.014). Higher EQ-VAS scores were independently related to MDT care (P=0.04), Rankin score (P=0.01), and psychological function (P<0.0001) but not to age, sex, or stroke severity. There were no significant differences in patient or caregiver satisfaction between the 2 settings.\n Better quality of life in patients receiving conventional MDT care may be attributable to improved social functioning and greater attention to higher function and caregiver needs during rehabilitation.", "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.", "This study describes the methodology, patient outcome, and use of hospital and rehabilitation services at 3 months of a population-based randomized controlled trial. The purpose was to evaluate rehabilitation at home after early supported discharge from the Department of Neurology, Huddinge Hospital, for moderately disabled stroke patients in southwest Stockholm.\n The patients were eligible if they were continent, independent in feeding, had mental function within normal limits, and had impaired motor function and/or aphasia 1 week after stroke. Patients were randomized either to early supported discharge with continuity of rehabilitation at home for 3 to 4 months or to routine rehabilitation service in a hospital, day care, and/or outpatient care. The home rehabilitation team consisted of two physical therapists, two occupational therapists, and one speech therapist; one of the therapists was assigned as case manager for the patient. The rehabilitation program at home emphasized a task- and context-oriented approach. The activities were chosen on the basis of the patient's personal interests. Spouses were offered education and individual counseling. A total of 81 patients were followed up for a minimum of 3 months. Patient outcome was assessed by the Frenchay Social Activity Index, Extended Katz Index, Barthel Index, Lindmark Motor Capacity Assessment, Nine-Hole Peg Test, walking speed over 10 m, reported falls, and subjective dysfunction according to the Sickness Impact Profile. Patient use of hospital and home rehabilitation service and patient satisfaction with care were studied.\n Overall there were no statistical significant differences in outcome. Multivariate logistic regression analysis suggested a systematic positive effect for the home rehabilitation group in social activity, activities of daily living, motor capacity, manual dexterity, and walking. A considerable difference in resource use during such a 3-month period was seen. A 52% reduction in hospitalization was observed: from 29 days in the routine rehabilitation group to 14 days in the home rehabilitation group. Patient satisfaction was in favor of the latter group.\n Early supported discharge with continuity of home rehabilitation services for the majority of moderately disabled stroke patients during the first 3-month period after acute stroke is not less beneficial than routine rehabilitation and can be a rehabilitation service of choice if follow-up at 6 and 12 months confirms the suggested effectiveness and considerable reduction in use of health care.", "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.", "To examine the effect of contact with a stroke family care worker on the physical, social, and psychological status of stroke patients and their carers.\n Randomised controlled trial with broad entry criteria and blinded outcome assessment six months after randomisation.\n A well organised stroke service in an Edinburgh teaching hospital.\n 417 patients with an acute stroke in the previous 30 days randomly allocated to be contacted by a stroke family care worker (210) or to receive standard care (207). The patients represented 67% of all stroke patients assessed at the hospital during the study period.\n Patient completed Barthel index, Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, mental adjustment to stroke scale, and patient satisfaction questionnaire; carer completed Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, caregiving bassles scale, and carer satisfaction questionnaire.\n The groups were balanced for all important baseline variables. There were no significant differences in physical outcomes in patients or carers, though patients in the treatment group were possibly more helpless less well adjusted socially, and more depressed, whereas carers in the treatment group were possibly less hassled and anxious. However, both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care, in particular those related to communication and support.\n The introduction of a stroke family care worker improved patients' and their carers' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients' physical wellbeing.", "Integrated Care Pathway (ICP) is an organized, goal-defined, and time-managed plan that has the potential of facilitating timely interdisciplinary coordination, improving discharge planning, and reducing length of hospital stay.\n An ICP for stroke rehabilitation based on evidence of best practice, professional standards, and existing infrastructure was developed. Its effectiveness was tested in 152 stroke patients undergoing rehabilitation who were randomized to receive ICP care coordinated by an experienced nurse (n=76) or conventional multidisciplinary care (n=76).\n The age, sex, premorbid functional ability, and stroke characteristics of the 2 groups were comparable. There were no differences in mortality rates (10 [13%] versus 6 [8%]), institutionalization (10 [13%] versus 16 [21%]), or length of hospital stay (50+/-19 versus 45+/-23 days) between patients receiving ICP or multidisciplinary care. Patients receiving conventional multidisciplinary care improved significantly faster between 4 and 12 weeks (median change in Barthel Activities of Daily Living Index 6 versus 2; P<0.01) and had higher Quality of Life scores at 12 weeks (65 versus 59; P=0.07) and 6 months (72 versus 63; P<0.005). There were no significant differences in the mean duration of physiotherapy (42.8+/-41.2 versus 39.4+/-36.4 hours) or occupational therapy (8.5+/-7.5 versus 8.0+/-7.5 hours) received between the 2 groups.\n ICP management offered no benefit over conventional multidisciplinary care on a stroke rehabilitation unit. Functional recovery was faster and Quality of Life outcomes better in patients receiving conventional multidisciplinary care.", "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.", "This paper reports a study evaluating whether expanding a specialist nursing role to provide outreach education and support to stroke patients and carers after discharge from hospital is effective in promoting recovery.\n Building therapeutic relationships with patients and carers is a key component of the nursing role in stroke rehabilitation, although this is limited by the constraints of service organization.\n A pragmatic randomized controlled trial was undertaken. Patients with a diagnosis of stroke were randomized to receive continued support from a stroke nurse (n = 87) or usual care and follow-up (n = 89) after discharge from hospital. Patients were recruited from two hospitals in the north-west of England from November 1999 to April 2001. Patient dependence (Barthel Index), general health (Nottingham Health Profile), activities of living (Frenchay Activity of Living Index), depression (Beck Depression Inventory) and carer strain (Carer Strain Index) were assessed at 3 and 12 months after stroke.\n The continued intervention of a stroke nurse after discharge was associated with improved patient perceptions of general health at 12 months (median difference 42.6, P = 0.012), and in particular reduced negative emotional reaction (P = 0.037) and perceived social isolation (P = 0.002). In addition, the intervention reduced carer strain at 3 months (P = 0.045), and reduced deterioration in physical dependence from 3 to 12 months (P = 0.049).\n The provision of continued intervention from a stroke nurse after discharge from hospital, focusing on education and support, has tangible benefits for patients and carers.", "Stroke patients are more likely to make a good recovery if they receive care in a well-organised stroke unit. However, there are uncertainties about how best to provide such care. We studied 2 key aspects of early stroke unit care: early active mobilisation (EM) and automated monitoring (AM) for physiological complications such as hypoxia.\n This was an observer-blinded, factorial (2 x 2) pilot randomised controlled trial recruiting stroke patients within 36 h of symptom onset. The patients were randomised to 1 of 4 nurse-led treatment protocols: (a) standard stroke unit care, (b) EM, (c) AM or (d) combined EM and AM. The primary outcome was the Rankin score at 3 months. We also report the data on feasibility and safety.\n We randomised 32 patients (mean age = 65 years; mean baseline modified NIH score = 6). On unadjusted comparisons, the EM patients were significantly (p < 0.05) more likely to mobilise very early (within 1 h of randomisation) and to achieve walking by day 5 and were less likely to develop complications of immobility. The AM group was significantly (p < 0.05) more likely to have pre-defined physiological complication events detected. All these associations remained, but were less statistically significant, after correcting for age, baseline NIH score and co-interventions. There were no significant safety concerns.\n We have demonstrated the feasibility of implementing EM and AM for physiological complications in a randomised controlled trial. Larger trials are warranted to determine whether these interventions have clinical benefits.\n (c) 2010 S. Karger AG, Basel." ]

[ "16822111", "21924563", "1861939", "17214891", "16893677", "15762903", "14687254", "12399345", "15249261" ]

[ "Internet-based health information consumer skills intervention for people living with HIV/AIDS.", "Adoption, reach and effectiveness of computer-based, practitioner delivered and combined smoking interventions in general medical practices: a three-arm cluster randomized trial.", "Increasing patient knowledge, satisfaction, and involvement: randomized trial of a communication intervention.", "Medical communication and technology: a video-based process study of the use of decision aids in primary care consultations.", "What factors are associated with the integration of evidence retrieval technology into routine general practice settings?", "Can computer-generated evidence-based care suggestions enhance evidence-based management of asthma and chronic obstructive pulmonary disease? A randomized, controlled trial.", "Effects of computerized guidelines for managing heart disease in primary care.", "Effect of computerised evidence based guidelines on management of asthma and angina in adults in primary care: cluster randomised controlled trial.", "Providing a web-based online medical record with electronic communication capabilities to patients with congestive heart failure: randomized trial." ]

[ "Medical information can improve health, and there is an enormous amount of health information available on the Internet. A randomized clinical trial tested the effectiveness of an intervention based on social- cognitive theory to improve information use among people living with HIV/AIDS. Men and women (N = 448) were placed in either (a) an 8-session intervention that focused on Internet information consumer skills or (b) a time-matched support group and were followed to 9 months postintervention. The Internet skills group demonstrated greater Internet use for health, information coping, and social support compared with the control group. The authors conclude that people with HIV infection may benefit from increased access to health information on the Internet and that vulnerability to misinformation and fraud can be reduced through behavioral interventions.\n Copyright 2006 APA, all rights reserved.", "Brief advice for smoking patients has not been sufficiently integrated in routine care. Computer-based interventions emerged as a time saving option that might help to exhaust the potential population impact of the general practice setting.\n 151 practices were randomly assigned to one of three intervention programs consisting in the delivery of: (1) brief advice by the practitioner; (2) individually tailored computer-generated letters; or (3) a combination of both interventions. We assessed three dimensions of population impact: (1) adoption, i.e., the rate of practices participating in the program; (2) reach, measured as the number of interventions provided within 7 months; (3) effectiveness, measured as smoking abstinence at 12-months follow-up.\n Among the practices, 70% adopted the program with no significant differences across study groups. Treatment was provided to 3086 adult smokers. Negative binomial regression analysis revealed that the number of interventions provided was higher in practices allocated to the tailored letter and combination intervention groups by 215% (p<.01) and 127% (p=.02), respectively, compared to the brief advice intervention group. Among the patients who received the combination of both intervention, the odds of point abstinence from smoking was increased by 65% (p=.02) and 32% (p=.01) compared to the brief advice and tailored letters intervention respectively. Comparing the number of abstinent patients at follow-up revealed that the tailored letter and combination interventions were superior to the brief advice intervention.\n Computer-based interventions alone or in addition to conventional practitioner-delivered advice can foster the participation of general medical practices in tobacco control.\n Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.", "A brief educational intervention to promote effective communication between physicians, children, and parents during pediatric office visits was designed and tested. A randomized clinical trial involving 141 children (5- to 15-year-olds) tested the effectiveness of the intervention to improve the process and outcome of medical care. The intervention was contained in three brief videotapes (one each for parents, physicians, and patients) and in accompanying written materials. Materials were designed to build skills and motivation for increased child competence and participation during pediatric medical visits. Control subjects saw health education videotapes and received materials comparable in length with those of experimental subjects. Postintervention medical visit process was analyzed using videotapes of visits. Visit outcomes, assessed with standardized instruments and interviews, included children's rapport with physicians, children's anxiety, children's preference for an active health role, children's recall of information, parents' satisfaction with the medical visit, and physician satisfaction. Results indicated that physicians in the intervention group, compared with their counterparts in the control group, more often included children in discussions of medical recommendations (50% vs 29%, t = 2.39, P less than .05); that children in the intervention group, compared with control children, recalled more medication recommendations (77% vs 47%, P less than .01) and reported greater satisfaction and preference for an active health role; and that the intervention and control groups did not differ in parent satisfaction, physician satisfaction, or child anxiety. The results suggest that a brief educational intervention administered during waiting room time can positively impact physician-child rapport and children's preference for an active role in health and their acquisition of medical information.", "Much of the research on decision-making in health care has focused on consultation outcomes. Less is known about the process by which clinicians and patients come to a treatment decision. This study aimed to quantitatively describe the behaviour shown by doctors and patients during primary care consultations when three types of decision aids were used to promote treatment decision-making in a randomised controlled trial.\n A video-based study set in an efficacy trial which compared the use of paper-based guidelines (control) with two forms of computer-based decision aids (implicit and explicit versions of DARTS II). Treatment decision concerned warfarin anti-coagulation to reduce the risk of stroke in older patients with atrial fibrillation. Twenty nine consultations were video-recorded. A ten-minute 'slice' of the consultation was sampled for detailed content analysis using existing interaction analysis protocols for verbal behaviour and ethological techniques for non-verbal behaviour.\n Median consultation times (quartiles) differed significantly depending on the technology used. Paper-based guidelines took 21 (19-26) minutes to work through compared to 31 (16-41) minutes for the implicit tool; and 44 (39-55) minutes for the explicit tool. In the ten minutes immediately preceding the decision point, GPs dominated the conversation, accounting for 64% (58-66%) of all utterances and this trend was similar across all three arms of the trial. Information-giving was the most frequent activity for both GPs and patients, although GPs did this at twice the rate compared to patients and at higher rates in consultations involving computerised decision aids. GPs' language was highly technically focused and just 7% of their conversation was socio-emotional in content; this was half the socio-emotional content shown by patients (15%). However, frequent head nodding and a close mirroring in the direction of eye-gaze suggested that both parties were active participants in the conversation\n Irrespective of the arm of the trial, both patients' and GPs' behaviour showed that they were reciprocally engaged in these consultations. However, even in consultations aimed at promoting shared decision-making, GPs' were verbally dominant, and they worked primarily as information providers for patients. In addition, computer-based decision aids significantly prolonged the consultations, particularly the later phases. These data suggest that decision aids may not lead to more 'sharing' in treatment decision-making and that, in their current form, they may take too long to negotiate for use in routine primary care.", "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.", "Translation of evidence-based guidelines into clinical practice has been inconsistent. We performed a randomized, controlled trial of guideline-based care suggestions delivered to physicians when writing orders on computer workstations.\n Inner-city academic general internal medicine practice.\n Randomized, controlled trial of 246 physicians (25 percent faculty general internists, 75 percent internal medicine residents) and 20 outpatient pharmacists. We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease. Care suggestions concerning drugs and monitoring were delivered to a random half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations. A 2 x 2 factorial randomization of practice sessions and pharmacists resulted in four groups of patients: physician intervention, pharmacist intervention, both interventions, and controls. DATA EXTRACTION/COLLECTION METHODS: Adherence to the guidelines and clinical activity was assessed using patients' electronic medical records. Health-related quality of life, medication adherence, and satisfaction with care were assessed using telephone questionnaires.\n During their year in the study, patients made an average of five scheduled primary care visits. There were no differences between groups in adherence to the care suggestions, generic or condition-specific quality of life, satisfaction with physicians or pharmacists, medication compliance, emergency department visits, or hospitalizations. Physicians receiving the intervention had significantly higher total health care costs. Physician attitudes toward guidelines were mixed.\n Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease.", "Electronic information systems have been proposed as one means to reduce medical errors of commission (doing the wrong thing) and omission (not providing indicated care).\n To assess the effects of computer-based cardiac care suggestions.\n A randomized, controlled trial targeting primary care physicians and pharmacists.\n A total of 706 outpatients with heart failure and/or ischemic heart disease.\n Evidence-based cardiac care suggestions, approved by a panel of local cardiologists and general internists, were displayed to physicians and pharmacists as they cared for enrolled patients.\n Adherence with the care suggestions, generic and condition-specific quality of life, acute exacerbations of their cardiac disease, medication compliance, health care costs, satisfaction with care, and physicians' attitudes toward guidelines.\n Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions. The intervention had no effect on physicians' adherence to the care suggestions (23% for intervention patients vs 22% for controls). There were no intervention-control differences in quality of life, medication compliance, health care utilization, costs, or satisfaction with care. Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients.\n Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease. Future studies must weigh the benefits and costs of different (and perhaps more Draconian) methods of affecting clinician behavior.", "To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care.\n A before and after pragmatic cluster randomised controlled trial utilising a two by two incomplete block design. Setting: 60 general practices in north east England.\n General practitioners and practice nurses in the study practices and their patients aged 18 or over with angina or asthma.\n Adherence to the guidelines, based on review of case notes and patient reported generic and condition specific outcome measures.\n The computerised decision support system had no significant effect on consultation rates, process of care measures (including prescribing), or any patient reported outcomes for either condition. Levels of use of the software were low.\n No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care. This was probably due to low levels of use of the software, despite the system being optimised as far as was technically possible. Even if the technical problems of producing a system that fully supports the management of chronic disease were solved, there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex, multiple conditions.", "It is possible to provide patients with secure access to their medical records using the Internet. Such access may assist patients in the self-management of chronic diseases such as heart failure.\n To assess how a patient-accessible online medical record affects patient care and clinic operations. The SPPARO (System Providing Access to Records Online) software consisted of a web-based electronic medical record, an educational guide, and a messaging system enabling electronic communication between the patient and staff.\n A randomized controlled trial was conducted in a specialty practice for patients with heart failure. Surveys assessing doctor-patient communication, adherence, and health status were conducted at baseline, 6 months, and 1 year. Use of the system, message volume, utilization of clinical services, and mortality were monitored.\n One hundred and seven patients were enrolled (54 intervention and 53 controls). At 12 months, the intervention group was not found to be superior in self-efficacy (KCCQ self-efficacy score 91 vs. 85, p=0.08), but was superior in general adherence (MOS compliance score 85 vs. 78, p=0.01). A trend was observed for better satisfaction with doctor-patient communication. The intervention group had more emergency department visits (20 vs. 8, p=0.03), but these visits were not temporally related to use of the online medical record. There were no adverse effects from use of the system.\n Providing patients with congestive heart failure access to an online medical record was feasible and improved adherence. An effect on health status could not be demonstrated in this pilot study." ]

[ "15774341", "15484202", "17785708", "7937251", "11879296", "11157015" ]

[ "A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment.", "Exercise manages fatigue during breast cancer treatment: a randomized controlled trial.", "Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.", "A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy.", "Fatigue and quality of life outcomes of exercise during cancer treatment.", "Structured exercise improves physical functioning in women with stages I and II breast cancer: results of a randomized controlled trial." ]

[ "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.", "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.", "Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects.\n We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema.\n The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem (P = .015), aerobic fitness (P = .006), and percent body fat (adjusted P = .076). Resistance exercise was superior to usual care for improving self-esteem (P = .018), muscular strength (P < .001), lean body mass (P = .015), and chemotherapy completion rate (P = .033). Changes in cancer-specific QOL, fatigue, depression, and anxiety favored the exercise groups but did not reach statistical significance. Exercise did not cause lymphedema or adverse events.\n Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy, but they did improve self-esteem, physical fitness, body composition, and chemotherapy completion rate without causing lymphedema or significant adverse events.", "To examine the effects of a comprehensive rehabilitation program on facilitating physical and psychosocial adaptation of women with breast cancer who are receiving adjuvant chemotherapy.\n Experimental.\n Breast evaluation clinics of two New England medical centers with comprehensive cancer treatment programs.\n 14 women (mean age = 44 years) receiving adjuvant chemotherapy for breast cancer (86% stage II) following surgical treatment.\n Subjects were assigned randomly to the experimental group or the usual care group. Experimental group members began a structured exercise program of walking and attended support group meetings. All subjects were tested before beginning chemotherapy, during the course of chemotherapy, and one month following chemotherapy completion.\n Performance status, physical functioning, psychosocial adjustment, self-concept and body image, and 12 symptoms (e.g., fatigue, nausea, anxiety).\n Measures of physical performance, psychosocial adjustment, and symptom intensity revealed improved adaptation in subjects who completed the walking/support group program.\n Physical and psychosocial benefits from a modest walking exercise program and a support group are possible for patients receiving adjuvant chemotherapy.\n Although more detailed research is necessary to answer some of the questions raised by this study, implementing the walking program and forming a support group are achievable in an outpatient setting.", "Despite the recognition of fatigue as a common and distressing symptom during cancer treatment, there are few evidence-based interventions available to manage such fatigue. The purpose of this multi-institutional pilot study was to explore the effects of a home-based moderate walking exercise intervention on fatigue, physical functioning, emotional distress, and quality of life (QOL) during breast cancer treatment.\n Fifty-two women were recruited from five university hospital outpatient departments for this pilot study with an experimental design. Subjects were randomly assigned to the walking program or to usual care during adjuvant chemotherapy or radiation therapy for breast cancer. Symptoms, physical functioning, and QOL were measured at baseline, midtreatment, and at the end of treatment.\n Women who exercised at least 90 minutes per week on 3 or more days reported significantly less fatigue and emotional distress as well as higher functional ability and QOL than women who were less active during treatment.\n A home-based walking exercise program is a potentially effective, low-cost, and safe intervention to manage fatigue and to improve QOL during adjuvant chemotherapy or radiation therapy for breast cancer. This health-promoting self-care activity needs further testing in large randomized clinical trials.", "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." ]

[ "18667099", "9210279", "17364418" ]

[ "Cognitive behaviour therapy for violent men with antisocial personality disorder in the community: an exploratory randomized controlled trial.", "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)." ]

[ "Little information exists on treatment effectiveness in antisocial personality disorder (ASPD). We investigated the feasibility and effectiveness of carrying out a randomized controlled trial of cognitive behaviour therapy (CBT) in men with ASPD who were aggressive.\n This was an exploratory two-centre, randomized controlled trial in a community setting. Fifty-two adult men with a diagnosis of ASPD, with acts of aggression in the 6 months prior to the study, were randomized to either treatment as usual (TAU) plus CBT, or usual treatment alone. Change over 12 months of follow-up was assessed in the occurrence of any act of aggression and also in terms of alcohol misuse, mental state, beliefs and social functioning.\n The follow-up rate was 79%. At 12 months, both groups reported a decrease in the occurrence of any acts of verbal or physical aggression. Trends in the data, in favour of CBT, were noted for problematic drinking, social functioning and beliefs about others.\n CBT did not improve outcomes more than usual treatment for men with ASPD who are aggressive and living in the community in this exploratory study. However, the data suggest that a larger study is required to fully assess the effectiveness of CBT in reducing aggression, alcohol misuse and improving social functioning and view of others. It is feasible to carry out a rigorous randomized controlled trial in this group.", "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." ]

[ "18055007", "15919846", "18155287", "8732700", "6437150" ]

[ "Transtheoretical model-based multiple behavior intervention for weight management: effectiveness on a population basis.", "Transtheoretical model-chronic disease care for obesity in primary care: a randomized trial.", "Initial efficacy of MI, TTM tailoring and HRI's with multiple behaviors for employee health promotion.", "Effectiveness of a behavioral weight control program for blacks and whites with NIDDM.", "Minimal interventions for weight control: a cost-effective alternative." ]

[ "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.", "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.", "This study was designed to compare the initial efficacy of Motivational Interviewing (MI), Online Transtheoretical Model (TTM)-tailored communications and a brief Health Risk Intervention (HRI) on four health risk factors (inactivity, BMI, stress and smoking) in a worksite sample.\n A randomized clinical trial assigned employees to one of three recruitment strategies and one of the three treatments. The treatment protocol included an HRI session for everyone and in addition either a recommended three TTM online sessions or three MI in person or telephone sessions over 6 months. At the initial post-treatment assessment at 6 months, groups were compared on the percentage who had progressed from at risk to taking effective action on each of the four risks.\n Compared to the HRI only group, the MI and TTM groups had significantly more participants in the Action stage for exercise and effective stress management and significantly fewer risk behaviors at 6 months. MI and TTM group outcomes were not different.\n This was the first study to demonstrate that MI and online TTM could produce significant multiple behavior changes. Future research will examine the long-term impacts of each treatment, their cost effectiveness, effects on productivity and quality of life and process variables mediating outcomes.", "To compare the weight losses of black and white patients with NIDDM treated in a year-long behavioral weight loss program.\n Subjects were randomly assigned to a behavioral program that either used a low-calorie diet throughout or included two 12-week periods of a very-low calorie diet (VLCD). Weight, dietary intake, and exercise were measured at 0, 6, and 12 months of treatment, and attendance and self-monitoring records were assessed weekly throughout the year.\n Blacks had smaller weight losses than whites regardless of treatment condition. Overall weight losses (baseline to 1 year) were 7.1 kg in blacks vs 13.9 kg in whites. The differences in overall outcome resulted primarily from greater weight regain in blacks during months 6-12 than in whites. There was a trend for blacks to have poorer attendance than whites during the latter half of the program and for blacks to report smaller changes in calorie intake from baseline to 6 months.\n The results confirm prior studies with nondiabetic patients showing smaller weight losses in blacks than in whites and suggest that these differences may result primarily from faster weight regain in blacks. Further research is needed to more carefully examine the variables that may explain this difference and to develop more effective programs for blacks with NIDDM.", "Two studies were conducted to evaluate simpler, less intensive interventions for weight control which presumably would be more cost-effective and efficient than a \"full-length\" behavioral treatment program. In Study 1, participants in a minimal intervention (MI1) program who attended no regularly scheduled meetings and initially only received three simple verbal instructions about how to lose weight, lost an average of 11.1 lb. by 7-month follow-up. Subjects in three variations of a shortened, less intensive, 6-week behavioral weight loss program lost 7.8, 6.5 and 6.3 lb. but did not significantly differ from MI1 subjects in the amount of weight lost. In Study 2, MI2 subjects lost 5.5 lb. compared to subjects in two variations of a full-length program who lost 8.1 and 11.1 lb. by 6-month follow-up. Again, none of the groups significantly differed from each other in the amount lost. It was concluded that a minimal intervention program seems to produce weight loss and to be a cost-effective and efficient method for some subjects. The difference between the two minimal intervention programs may be related to the payment of a monetary deposit; a model for future research was presented to investigate simpler, less intensive interventions in combination with more complex ones in a \"stepped-care\" fashion." ]

[ "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", "7508066" ]

[ "Forced versus minimal intravenous hydration in the management of acute renal colic: a randomized trial.", "Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences." ]

[ "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.", "We examined the biochemical changes and the efficacy of indapamide in the prevention of calcium stone recurrences. Seventy-five patients with calcium nephrolithiasis and hypercalciuria were randomly assigned to three different therapies: diet and fluid (group A), diet and fluid plus indapamide 2.5 mg/day (group B), and diet and fluid plus indapamide 2.5 mg/day plus allopurinol 300 mg/day (group C). Before treatment and after 6, 12, 24, and 36 months of therapy, we evaluated blood pressure, serum and urine risk parameters (including relative supersaturations of calcium oxalate, calcium phosphate and uric acid), stone rate, and the proportion of calculi-free patients. During the 3 years of treatment, urinary calcium greatly decreased in groups B and C, dropping to 50% of the pretreatment values; urinary oxalate also significantly declined in group B (-24%) and group C (-27%). Relative supersaturations of calcium oxalate and calcium phosphate decreased to the same extent in groups B and C (about one-half of the pretreatment value), and relative supersaturation of uric acid was particularly reduced in group C (-65% of the pretreatment value). The stone rate improved in all three groups (p < 0.005), but using actuarial analysis in the evaluation of calculi-free patients, indapamide, and indapamide plus allopurinol groups were found to have a significantly more favorable effect than diet and fluid treatment (p < 0.02), without any difference between the two drug groups. Because indapamide has fewer side effects than thiazide diuretics, we conclude that indapamide could be an interesting alternative to thiazides in the prevention of calcium stones in hypercalciuric patients." ]

[ "11431176" ]

[ "Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy." ]

[ "Angiotensin-converting enzyme (ACE) inhibitors and AT1-receptor antagonists (ARAs) are widely administered to reduce urinary protein loss and slow the progression of proteinuric nephropathy to end-stage renal failure. Our group recently observed that the combination of ACE inhibitors and ARAs may have an additive antiproteinuric effect, which may occur because ACE inhibitors do not completely reduce angiotensin II (Ang II) production. Ang II is also produced by chymase. Thus, combination therapy better antagonizes the effects of Ang II. The purpose of this study is to ascertain whether the additive antiproteinuric effect of ACE inhibitors plus ARAs is dose dependent and related to the drug-induced reduction in systemic blood pressure. Therefore, enalapril (E; 10 mg/d) and losartan (LOS; 50 mg/d) were randomly administered alone and then in association; initial dosages were doubled when drugs were administered alone and in association. To determine the influence of the drug-dependent effect on reducing blood pressure and the reduction in urinary proteinuria, both ambulatory and office blood pressures were recorded. E and LOS administered alone reduced proteinuria by the same extent; no further reduction was observed when E and LOS alone were administered at a doubled dose. When E and LOS were coadministered, proteinuria decreased by a greater extent compared with E and LOS alone; an additional reduction in proteinuria was observed when combined therapy doses were doubled. The reduction in proteinuria was not correlated with clinical through blood pressure; however, reductions in diastolic and mean ambulatory blood pressures significantly correlated with the decrease in proteinuria, as well as with creatinine clearance. In conclusion, this study shows that combination therapy with E and LOS has an additive dose-dependent antiproteinuric effect that is likely induced by the drug-related reduction in systemic blood pressure. In normotensive proteinuric patients, it is likely that even a small reduction in systemic blood pressure may affect intraglomerular hemodynamics by a great extent because efferent arteriole regulation is hampered more completely by the coadministration of ACE inhibitors and ARAs." ]

[ "18237352", "18755784", "10117742", "19775439", "9097333", "7974314" ]

[ "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "Promotion of health in older people: a randomised controlled trial of health risk appraisal in British general practice.", "The impact of increasing intensity of health promotion intervention on risk reduction.", "A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies.", "Psychophysiological concomitants of organizational change in health care personnel: effects of a controlled intervention study.", "Prospective controlled evaluation of the effect of a community based asthma education centre in a multiracial working class neighbourhood." ]

[ "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation.", "there is inadequate evidence to support currently formulated NHS strategies to achieve health promotion and preventative care in older people through broad-based screening and assessment in primary care. The most extensively evaluated delivery instrument for this purpose is Health Risk Appraisal (HRA). This article describes a trial using HRA to evaluate the effect on health behaviour and preventative-care uptake in older people in NHS primary care.\n a randomised controlled trial was undertaken in three London primary care group practices. Functionally independent community-dwelling patients older than 65 years (n = 2,503) received a self-administered Health Risk Appraisal for Older Persons (HRA-O) questionnaire leading to computer-generated individualised written feedback to participants and general practitioners (GPs), integrated into practice information-technology (IT) systems. All primary care staff received training in preventative health in older people. The main outcome measures were self-reported health behaviour and preventative care uptake at 1-year follow-up.\n of 2,503 individuals randomised, 2,006 respondents (80.1%) (intervention, n = 940, control n = 1,066) were available for analysis. Intervention group respondents reported slightly higher pneumococcal vaccination uptake and equivocal improvement in physical activity levels compared with controls. No significant differences were observed for any other categories of health behaviour or preventative care measures at 1-year follow-up.\n HRA-O implemented in this way resulted in minimal improvement of health behaviour or uptake of preventative care measures in older people. Supplementary reinforcement involving contact by health professionals with patients over and above routine clinical encounters may be a prerequisite to the effectiveness of IT-based delivery systems for health promotion in older people.", "The HealthWise Stepped Intervention Study (1988-1990) at Pacific Gas and Electric was conducted to evaluate how a health promotion program affects behavior change and whether increasing levels of preventive interventions improve health status. The basic intervention components consisted of health risk assessment and health newsletter (Levels 1, 2, 3, and 4). Additional interventions were health resource center and self-care books (Levels 2, 3, and 4), behavioral change workshops and Division Healthwise team (Levels 3 and 4), and case management and environmental policy (Level 4). The study employed a quasi-experimental design with nonequivalent control groups. The overall risk status has significantly improved at all four intervention levels. The comparison across the four intervention levels found that Level 4, combining environmental policy with \"high risk\" targeting, showed the most impressive performance. Participants in Level 4 consistently showed significantly greater improvement in life-style factors, and their overall risk status also showed the greatest improvement.", "Significant resources and time are invested in the production of research knowledge. The primary objective of this randomized controlled trial was to evaluate the effectiveness of three knowledge translation and exchange strategies in the incorporation of research evidence into public health policies and programs.\n This trial was conducted with a national sample of public health departments in Canada from 2004 to 2006. The three interventions, implemented over one year in 2005, included access to an online registry of research evidence; tailored messaging; and a knowledge broker. The primary outcome assessed the extent to which research evidence was used in a recent program decision, and the secondary outcome measured the change in the sum of evidence-informed healthy body weight promotion policies or programs being delivered at health departments. Mixed-effects models were used to test the hypotheses.\n One hundred and eight of 141 (77%) health departments participated in this study. No significant effect of the intervention was observed for primary outcome (p < 0.45). However, for public health policies and programs (HPPs), a significant effect of the intervention was observed only for tailored, targeted messages (p < 0.01). The treatment effect was moderated by organizational research culture (e.g., value placed on research evidence in decision making).\n The results of this study suggest that under certain conditions tailored, targeted messages are more effective than knowledge brokering and access to an online registry of research evidence. Greater emphasis on the identification of organizational factors is needed in order to implement strategies that best meet the needs of individual organizations.\n The trial registration number and title are as follows: ISRCTN35240937 -- Is a knowledge broker more effective than other strategies in promoting evidence-based physical activity and healthy body weight programming?", "To assess possible psychophysiological changes in personnel being exposed to organizational change and to assess the effects of a structured empowerment programme.\n A randomized, prospective, controlled, and non-blinded intervention was carried out in two wards within a geriatric hospital. The I-ward (intervention) was offered a structured intervention programme with a trained, registered psychologist during 20 weekly 1-hour sessions before and after the organizational change. The C-ward (control) was passively attended by the same psychologist during equal time conditions. Blood pressure as well as pulse rate were taken and blood samples were drawn from all participants before (0 weeks), immediately after the intervention (20 weeks) and after another 10 weeks' follow-up (30 weeks).\n There was a significant time x group interaction with increasing prolactin levels on the C-ward as compared to decreasing levels on the I-ward during the intervention.\n Our study results suggest a picture of differentiated changes in stress hormone levels. The I-ward exhibited less psychoendocrine stress compared to the C-ward, probably due to the intervention and the possibility for personnel to influence the programme. We suggest that psychosocial empowerment programmes are beneficial when organizational changes are enacted in health care settings.", "Previous work has indicated a high rate of non-attendance at hospital based clinics among young, multiracial asthmatic patients of lower socioeconomic class. The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated.\n A prospective controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were randomised to the usual follow up or the education centre plus usual follow up. Measurements were taken at entry into the study and again nine months later.\n At nine months patients randomised to the education centre had more preventive medications, more peak expiratory flow meters and better flow meter technique, more self-management plans, better knowledge of appropriate action to take when confronted with worsening asthma, less nocturnal awakening, and better self-reported asthma control than the control group. There was no difference between the study groups in measurements of compliance, hospital admission, days lost from school or work, or emergency room use.\n The main effects of education were on asthma knowledge and self-management skills, whilst improvements in asthma morbidity were small. Potential reasons for this include heterogeneous study population (in terms of baseline self-management skills, asthma severity, ethnicity and age), pragmatic study design, insensitivity of many of the measurements of morbidity, the modest effectiveness of a single time limited education programme, and inability to limit the effects of such a large community based study to the intervention group (there was a 67% reduction in asthma admissions during the study period from the geographical area targeted compared with a 22% reduction for the rest of Auckland)." ]

[ "16500364" ]

[ "Addition of human chorionic gonadotropin to clomiphene citrate ovulation induction therapy does not improve pregnancy outcomes and luteal function." ]

[ "In a randomized prospective study, 125 women with World Health Organization class II anovulation received 50 mg of clomiphene citrate alone (group A, n = 65) or 50 mg of clomiphene citrate plus hCG (group B, n = 60) in a total of 125 cycles during natural intercourse-advised cycles. There were no statistically significant differences between groups regarding pregnancy outcomes and midluteal P levels, but luteal phase length was longer in group A." ]

[ "12893670", "16585434" ]

[ "Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment." ]

[ "Although there is a consensus that clozapine is more effective than conventional antipsychotic drugs for treatment-resistant schizophrenia, there is great heterogeneity among results of relevant trials.\n To re-evaluate the evidence comparing clozapine with conventional antipsychotics and to investigate sources of heterogeneity.\n Individual studies were inspected with assessment of clinical relevance of results. Meta-regression analysis was performed to investigate sources of heterogeneity.\n Ten trials were examined. Recent large-scale studies have not found a substantial advantage for clozapine, especially in terms of a clinically relevant effect. Meta-regression showed that shorter study duration, financial support from a drug company and higher baseline symptom score consistently predicted greater advantage of clozapine.\n It may be inappropriate to combine studies in meta-analysis, given the degree of heterogeneity between their findings. The benefits of clozapine compared with conventional treatment may not be substantial.", "When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.\n Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).\n Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.\n For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects." ]

[ "9915528", "10528595", "10327093" ]

[ "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 study of ultrasound therapy in the management of acute lateral ligament sprains of the ankle joint." ]

[ "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.", "To determine the efficacy of a fixed dose of ultrasound energy to treat acute lateral ligament sprains of the ankle joint.\n Double-blind randomised controlled trial.\n Accident and Emergency department of University Teaching Hospital.\n Patients presenting at Accident and Emergency with ankle injuries.\n Ultrasound or placebo, and Tubigrip.\n Pain measured with visual analogue scales, swelling using a tape measure, range of movement using a fluid-filled goniometer, and weight bearing using two scales simultaneously.\n Patients in both groups improved symptomatically. There were no statistically significant differences between groups in any outcome measure. Within groups, statistically significant differences were detected in pain perceived, and range of movement (dorsiflexion).\n At the dose and duration used, ultrasound therapy is no better than placebo in the management of lateral ligament injuries." ]

[ "11356585", "11729030", "18162017", "9232667", "9850359", "10334524", "9404747", "10522500" ]

[ "Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia.", "A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia.", "Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial.", "Evaluation of antitussive agents in man.", "Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma.", "Safety and efficacy of using a single agent or a phase II agent before instituting standard combination chemotherapy in previously untreated metastatic breast cancer patients: report of a randomized study--Cancer and Leukemia Group B 8642.", "Routine nebulized ipratropium and albuterol together are better than either alone in COPD. The COMBIVENT Inhalation Solution Study Group.", "Use of topical ascorbic acid and its effects on photodamaged skin topography." ]

[ "Evidence that the metabolism of phospholipids and polyunsaturated fatty acids (PUFA) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation. An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies. The first study was designed to distinguish between the possible effects of two different n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA, DHA or placebo for 3 months. Improvement on EPA measured by the Positive and Negative Syndrome Scale (PANSS) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS. EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures. In the second placebo-controlled study, EPA was used as a sole treatment, though the use of antipsychotic drugs was still permitted if this was clinically imperative. By the end of the study, all 12 patients on placebo, but only eight out of 14 patients on EPA, were taking antipsychotic drugs. Despite this, patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study. It is concluded that EPA may represent a new treatment approach to schizophrenia, and this requires investigation by large-scale placebo-controlled trials.", "This study determined if augmentation of neuroleptics with 3 g/day of ethyl eicosapentaenoic acid (EPA) improves symptoms and cognition in patients with schizophrenia or schizoaffective disorder.\n Eighty-seven patients meeting criteria for schizophrenia or schizoaffective disorder who had residual symptoms despite neuroleptic treatment were randomly assigned to receive either 3 g/day of ethyl EPA (N=43) or placebo (N=44) in a 16-week, double-blind supplementation trial. Assessments were performed at baseline and at weeks 1, 2, 4, 8, 12, and 16; a cognitive battery was administered at baseline and at week 16.\n No differences were found between groups in positive or negative symptoms, mood, cognition, or global impression ratings. Results were similar for the intention-to-treat (N=87) and completer (N=75) groups.\n For schizophrenia patients treated with 3 g/day of ethyl EPA, improvement in residual symptoms and cognitive impairment was no greater than for schizophrenia patients treated with placebo.", "To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP).\n We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures.\n Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all timepoints), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone.\n The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted.\n Australian Clinical Trials Registry identifier 12605000267651 (http://actr.org.au).", "Methodology to evaluate the efficacy of antitussive drugs rely largely on subjective methods and cough counts. There are few studies in cough due to natural disease especially using objective techniques. This paper presents data from a series of randomized, double blind, placebo controlled clinical trials in cough due to both chronic bronchopulmonary disease and acute upper respiratory tract infections. In these studies, cough was quantified using a standardized and validated computerized system for the acquisition and multidimensional analysis of the cough sound. Key objective parameters like cough counts, intensity, latency and total effort expended were studied. Guaiphenesin and bromhexine showed significant expectorant effects in patients with productive cough due to chronic bronchopulmonary disease. Differences were observed in speed of action, and objective and subjective measures, that probably indicate differences in drug action. More recently, three studies evaluated the antitussive drug dextromethorphan in non-productive cough due to uncomplicated upper respiratory tract infections. Reproducible cough suppressant effects were demonstrated after a single 30 mg dose using objective measures of cough counts, latency and total effort. These results establish the sensitivity and robustness of the cough quantitation methodology in the objective evaluation of cough treatments.", "Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.", "We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients.\n A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF.\n The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm.\n The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.", "We compared the long-term safety and efficacy of the combination ipratropium bromide (IB) and albuterol sulfate (ALB) inhalation solution with that of each separate component using three-times-daily administration.\n Using a parallel design, we randomized patients to receive 3.0 mg ALB, 0.5 mg IB, or the combination by small-volume nebulizer (SVN) for 85 days. Subjects were allowed to use up to two extra doses of study medication daily for control of symptoms on an as-needed basis. The main efficacy evaluation was the acute pulmonary function response to an aerosol of the maintenance study medication over the course of the investigation. Physician global evaluation, subject quality of life assessments, COPD symptom scores, and twice-daily peak expiratory flow rate (PEFR) were also assessed over the study period.\n Twenty-five centers participated in the investigation.\n We studied 652 patients with moderate to severe COPD.\n Over the course of the study, the acute spirometric response and evening PEFR values with the SVN combination of IB plus ALB were statistically significantly better compared to ALB or IB alone. The quality of life scores, physician global evaluations, symptom scores, and morning PEFR scores were unchanged over the duration of the study in all treatment groups. There was no significant difference in adverse events in the three treatment groups.\n In patients with COPD, maintenance SVN therapy with IB and ALB provides better bronchodilation than either therapy alone without increasing side effects.", "To determine the efficacy of topical ascorbic acid application in treating mild to moderate photodamage of facial skin using an objective, computer-assisted image analysis of skin surface topography and subjective clinical, photographic, and patient self-appraisal questionnaires.\n A 3-month, randomized, double-blind, vehicle-controlled study.\n Facial plastic surgery private practice.\n Nineteen evaluable volunteer sample patients aged between 36 and 72 years with Fitzpatrick skin types I, II, and III who were in good physical and mental health with mild to moderately photodamaged facial skin were considered for analysis.\n Coded, unmarked medications were randomly assigned to the left and right sides of each subject's face, one containing the active agent, topical ascorbic acid (Cellex-C high-potency serum; Cellex-C International, Toronto, Ontario), the other, the vehicle serum (Cellex-C International). Three drops (0.5 mL) of each formulation were applied daily to the randomly assigned hemifaces over the 3-month study period. Treatment assignments were not disclosed to subjects, clinicians, or personnel involved in analyzing skin replicas.\n Specific clinical parameters were evaluated and graded on a 0- to 9-point scale (0, none; 1-3, mild; 4-6, moderate; and 7-9, severe). Reference photographs were used to standardize grading criteria. Overall investigator scores were compared with baseline and graded as excellent (much improved), good (improved), fair (slightly improved), no change, or worse. Patient self-appraisal questionnaires rated the degree of improvement (much improved, improved, slightly improved, no change, or worse) and reported adverse effects (burning, stinging, redness, peeling, dryness, discoloration, itching, and rash). Standard photographs were taken at baseline, including anteroposterior and left and right oblique views to facilitate subsequent clinical evaluations, and at the end of therapy for comparison. Optical profilometry analysis was performed on the skin surface replicas of the lateral canthal (crow's feet) region, comparing baseline to end-of-study specimens. Using this computer-based system, the resulting image was digitally analyzed, and numeric values were assigned to reflect surface features. The parameters obtained included Rz, Ra, and shadows. These values provided objective data that document pretreatment and posttreatment texture changes proportional to the degree of wrinkling, roughness, and other surface irregularities.\n Optical profilometry image analysis demonstrated a statistically significant 73.7% improvement in the Ra and shadows north-south facial axis values with active treatment greater than vehicle control, as well as a trend for improvement in the Rz north-south facial axis parameter, showing a 68.4% greater improvement of active treatment vs vehicle control. Clinical assessment demonstrated significant improvement with active treatment greater than control for fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone, sallowness/yellowing, and overall features. Patient questionnaire results demonstrated statistically significant improvement overall, active treatment 84.2% greater than control. Photographic assessment demonstrated significant improvement, active treatment 57.9% greater than control.\n A 3-month daily regimen of topical ascorbic acid provided objective and subjective improvement in photodamaged facial skin. Skin replica optical profilometry is an objective method for quantification of the skin surface texture changes." ]

[ "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." ]

[ "17388666", "16919803", "9388397" ]

[ "Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe.", "A brief individualized computer-delivered sexual risk reduction intervention increases HIV/AIDS preventive behavior.", "Randomised, controlled, community-level HIV-prevention intervention for sexual-risk behaviour among homosexual men in US cities. Community HIV Prevention Research Collaborative." ]

[ "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.", "One objective of translational science is to identify elements of human immunodeficiency virus (HIV) risk-reduction interventions that have been shown to be effective and find new ways of delivering these interventions to the community to ensure that they reach the widest possible audience of at-risk individuals. The current study reports the development and evaluation of a computer-delivered, theory-based, individually tailored HIV risk-reduction intervention.\n This study evaluated the effectiveness of a custom computerized HIV/AIDS risk reduction intervention at increasing HIV/AIDS preventive behaviors in a randomized trial with 157 college students. The intervention content and delivery were based on the Information-Motivation-Behavioral Skills Model of Health Behavior Change and used Motivational Interviewing techniques. Participants completed a baseline assessment of HIV prevention information, motivation, behavioral skills and behavior, attended two brief computer-delivered intervention sessions, and completed a follow-up assessment.\n As compared to the control group (a nutrition education tutorial), participants who interacted with the computer-delivered HIV/AIDS risk reduction intervention exhibited a significant increase in risk reduction behavior. Specifically, participants reported a greater frequency of keeping condoms available and displayed greater condom-related knowledge at a four-week follow-up session; among sexually active participants, there was a significant increase in self-reported condom use.\n Delivery of brief individually tailored HIV/AIDS risk reduction interventions via computer may be an effective HIV/AIDS prevention approach for adolescents. More research is needed to further support the effectiveness of this type of intervention and determine the generalizability of these findings to economically and educationally disadvantaged adolescents.", "Community-level interventions may be helpful in population-focused HIV prevention. If members of populations at risk of HIV infection who are popular with other members can be engaged to advocate the benefits of behaviour change to peers, decreases in risk behaviour may be possible. We assessed a community-level intervention to lower the risk of HIV infection, focusing on men patronising gay bars in eight small US cities.\n We used a randomised community-level field design. Four cities received the intervention and four control cities did not. Participants were men from each city who went to gay bars. Men completed surveys about their sexual behaviour on entering the bars during 3-night periods at baseline and at 1-year follow-up. In the control cities, HIV educational materials were placed in the bars. In the intervention cities, we recruited popular homosexual men in the community and trained them to spread behaviour-change endorsements and recommendations to their peers through conversation.\n Population-level of risk behaviour decreased significantly in the intervention cities compared with the control cities at 1-year follow-up, after exclusion of surveys completed by transients and men with exclusive sexual partners in a city-level analysis, in the intervention cities we found a reduction in the mean frequency of unprotected anal intercourse during the previous 2 months (baseline 1.68 occasions; follow-up 0.59: p = 0.04) and an increase in the mean percentage of occasions of anal intercourse protected by condoms (baseline 44.7%; follow-up 66.8%, p = 0.02). Increased numbers of condoms taken from dispensers in intervention-city bars corroborated risk-behaviour self-reports.\n Popular and well-liked members of a community who systematically endorse and recommend risk-reduction behaviour can influence the sexual-risk practices of others in their social networks. Natural styles of communication, such as conversations, brought about population-level changes in risk behaviour." ]

[ "9870617", "17227922" ]

[ "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 randomized controlled trial of laparoscopic nissen fundoplication versus proton pump inhibitors for treatment of patients with chronic gastroesophageal reflux disease: One-year follow-up." ]

[ "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).", "A randomized controlled trial conducted in patients with gastroesophageal reflux disease compared optimized medical therapy using proton pump inhibitor (n = 52) with laparoscopic Nissen fundoplication (n = 52). Patients were monitored for 1 year. The primary end point was frequency of gastroesophageal reflux dis-ease symptoms. Surgical patients had improved symptoms, pH control, and overall quality of life health index after surgery at 1 year compared with the medical group. The overall gastroesophageal reflux disease symptom score at 1 year was unchanged in the medical patients, but improved in the surgical patients. Fourteen patients in the medical arm experienced symptom relapse requiring titration of the proton pump inhibitor dose, but 6 had satisfactory symptom remission. No surgical patients required additional treatment for symptom control. Patients controlled on long-term proton pump inhibitor therapy for chronic gastroesophageal reflux disease are excellent surgical candidates and should experience improved symptom control after surgery at 1 year." ]

[ "15654136", "9688391", "8299789", "10099977", "7558391", "10615885", "19531445", "8822431", "7962385", "2065789", "8425628", "10521098" ]

[ "A randomised prospective trial of intrauterine insemination versus timed intercourse in superovulated cycles with clomiphene.", "Controlled ovarian hyperstimulation and intrauterine insemination for treating male subfertility: a controlled study.", "Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles.", "The clinical efficacy of low-dose step-up follicle stimulating hormone administration for treatment of unexplained infertility.", "Intrauterine insemination of washed spermatozoa for treatment of oligozoospermia.", "Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis.", "A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial.", "Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility.", "Clinical pregnancy and male subfertility; the ESHRE multicentre trial on the treatment of male subfertility. European Society of Human Reproduction and Embryology.", "A prospective trial of intrauterine insemination of motile spermatozoa versus timed intercourse.", "Comparison of intracervical, intrauterine, and intratubal techniques for donor insemination.", "Efficacy of double intrauterine insemination in controlled ovarian hyperstimulation cycles." ]

[ "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.", "In this randomized crossover trial we investigated whether the use of controlled ovarian hyperstimulation with low-dose human menopausal gonadotrophin in couples with male subfertility leads to a higher probability of conception when intrauterine insemination (IUI) is applied. We also investigated whether the efficacy of IUI in natural or stimulated cycles was related to the severity of male subfertility. Seventy-four couples completed 308 treatment cycles. Thirteen pregnancies occurred after IUI in a natural cycle (pregnancy rate per completed cycle: 8.4%) and 21 after IUI in a stimulated cycle (pregnancy rate per completed cycle: 13.7%). The difference between the two treatment modalities was not statistically significant. The efficacy of IUI in stimulated cycles was related to the severity of the semen defect. In couples with a total motile sperm count < 10 x 10(6), ovarian stimulation did not improve treatment outcome, while it did in couples with a total motile sperm count > or = 10 x 10(6). Compared with the expected chance of conceiving spontaneously without treatment, both natural and stimulated cycles improved the probability of conception. We conclude that, for the group as a whole, ovarian stimulation did not improve the probability of conception. However, in couples with less severe semen defects, ovarian stimulation did improve the probability of conception.", "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.", "The present study was designed to compare the clinical efficacy of low-dose step-up follicle stimulating hormone (FSH) administration with conventional FSH protocol (FSH was injected daily starting with a dose of 150 IU), both combined with intrauterine insemination (IUI), for the treatment of unexplained infertility. A total of 97 unexplained infertility couples was randomly assigned to one or other of the two treatment groups, either conventional FSH with IUI (48 patients) or low-dose step-up FSH with IUI (49 patients), and only the first treatment cycle was evaluated in each protocol. The difference in pregnancy rates per cycle was not statistically significant between the low-dose FSH group and the conventional group [seven of 49 (14.3%) and seven of 48 (14.6%) respectively]. A significant reduction in the incidence of ovarian hyperstimulation syndrome (OHSS) was observed in the low-dose group (8.3% versus 27.1%, P < 0.05). The incidence of moderate OHSS requiring hospitalization was reduced significantly in the low-dose group (low-dose 0% versus conventional 16.7%, P < 0.01). However, the low-dose protocol did not completely prevent multiple pregnancies. Our results suggest that the low-dose step-up FSH treatment appeared to be useful for the treatment of unexplained infertility because of the high pregnancy rates and the significant decrease in the incidence of OHSS.", "Efficacy of intrauterine insemination (IUI) using washed spermatozoa for treatment of oligozoospermia was evaluated by a prospective randomized study in 50 couples, using LH-timed natural intercourse in the alternate menstrual cycles as a control. The quality of spermatozoa in terms of their concentration and motility before and after sperm washing was compared. Sperm motility increased significantly after sperm preparation but the number of sperm was reduced. Eight pregnancies occurred in 253 cycles of IUI with washed spermatozoa and clomiphene citrate-stimulated cycles (3.16% per cycle). Only one patient conceived in 242 LH-timed natural intercourse cycles (0.41% per cycle). Compared with LH-timed natural intercourse, IUI provided a significantly improved pregnancy rate. When the sperm count was < 5 x 10(6) per ml, no pregnancy occurred with the IUI method. Therefore, IUI is a of rather limited usefulness when the sperm quality is very poor. Few complications occurred after IUI, but included slight cervical contact bleeding and mild abdominal discomfort and/or cramps. In conclusion, IUI should be considered as a useful and relatively non-invasive therapeutic modality for treating caused by moderate oligozoospermia (> 5 x 10(6)/ml), when sexual intercourse fails.", "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.", "To determine the value of gonadotropin/intrauterine insemination (FSH/IUI) therapy for infertile women aged 21-39 years.\n Randomized controlled trial.\n Academic medical center associated with a private infertility center.\n Couples with unexplained infertility.\n Couples were randomized to receive either conventional treatment (n=247) with three cycles of clomiphene citrate (CC)/IUI, three cycles of FSH/IUI, and up to six cycles of IVF or an accelerated treatment (n=256) that omitted the three cycles of FSH/IUI.\n The time it took to establish a pregnancy that led to a live birth and cost-effectiveness, defined as the ratio of the sum of all health insurance charges between randomization and delivery divided by the number of couples delivering at least one live-born baby.\n An increased rate of pregnancy was observed in the accelerated arm (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.00-1.56) compared with the conventional arm. Median time to pregnancy was 8 and 11 months in the accelerated and conventional arms, respectively. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. Average charges per delivery were $9,800 lower (95% CI, $25,100 lower to $3,900 higher) in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of $2,624 per couple for accelerated treatment and 0.06 more deliveries.\n A randomized clinical trial demonstrated that FSH/IUI treatment was of no added value.\n Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "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.", "Ovulation induction alone, and ovulation induction in conjunction with one of four assisted procreation methods [intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF)] were tested as a treatment for male infertility in a prospective randomized trial. The trial when completed had generated data on 499 cycles from 346 patients. There was overwhelming evidence that some form of assisted procreation was beneficial, when compared to the spontaneous natural conception rate, which is generally assumed to be between 0.01 and 0.02 for male infertility. There was also firm evidence that IUI, GIFT or IVF (mean per cycle pregnancy rate 0.212) were superior to the remaining two treatments of IPI and ovulation induction alone (mean per cycle pregnancy rate 0.068). Duration of infertility and a diagnosis of endometriosis were the most important (adverse) pre-treatment factors detected.", "The efficacy of intrauterine insemination (IUI) of selected motile sperm.\n Prospective randomized sequential alternating cycle trial comparing IUI with luteinizing hormone (LH)-timed intercourse.\n Clinical infertility service.\n Couples selected included unexplained infertility (n = 73), cervical mucus hostility (n = 24), moderate semen defect (n = 110), and severe semen defect (n = 78). Two hundred eighty-five couples undertook 600 IUI cycles and 505 LH-timed intercourse.\n Overall, IUI was slightly more effective than LH-timed intercourse with a pregnancy rate of 6.2% versus 3.4% per cycle. When individual categories were considered only, IUI for severe semen defect was significantly better (5.6% versus 1.3%, P less than 0.05). The first IUI cycle was more effective when compared with both subsequent IUI cycles and the initial LH-timed cycle. Overall, 74% (27/37) of IUI pregnancies occurred in the first cycle.\n Compared with LH-timed intercourse, IUI provided little or no improved expectation of pregnancy but was beneficial in couples with severe semen defect. The occurrence of pregnancy was limited per cycle and confined essentially to the initial cycle of treatment. Continued IUI is considered to be unrewarding.", "To compare the efficacy of intracervical insemination (ICI), intrauterine insemination (IUI), and a combination of intratubal and intrauterine insemination (ITI/IUI) for donor insemination.\n Prospective randomized clinical trial.\n The University of Michigan donor insemination program.\n Forty-one women undergoing donor insemination with cryopreserved sperm for either isolated male factor or male factor plus ovulatory dysfunction corrected by clomiphene citrate.\n Each patient was randomly assigned to receive each of the three insemination techniques in consecutive cycles until pregnancy occurred or the patient dropped from the study.\n Cycle fecundity rates were compared using the chi 2 test, and cumulative pregnancy rates (PRs) determined by life table analysis were compared using a log-rank test.\n Cycle fecundity rate was significantly higher for IUI (18.3%) than for ICI (3.9%) or ITI/IUI (7.3%). By life table analysis, the cumulative PR for IUI was significantly higher than for ICI, but the PR for ITI/IUI was not.\n For donor insemination with cryopreserved sperm, IUI increases cycle fecundity compared with ICI. The addition of ITI to IUI, however, interferes with the apparent beneficial effect of IUI alone.", "To investigate the effectiveness of double IUI and to determine the optimal timing of IUI in relation to hCG administration.\n Prospective randomized study.\n Infertility Center, Department of Obstetrics and Gynecology, University of Milan.\n Patients with male factor and unexplained infertility undergoing controlled ovarian hyperstimulation (COH) and IUI.\n After COH with clomiphene citrate and gonadotropins, patients were randomly assigned to one of the following groups: group A received a single IUI 34 hours after hCG administration, group B received a double IUI 12 hours and 34 hours after hCG administration, and group C received a double IUI 34 hours and 60 hours after hCG administration.\n Number of follicles > 15 mm in diameter on the day of hCG administration, number of motile spermatozoa inseminated, clinical pregnancy rate.\n Two hundred seventy-three patients underwent 449 treatment cycles: 90 patients were treated for 156 cycles in group A, 92 patients for 144 cycles in group B, and 91 patients for 149 cycles in group C. The overall pregnancies rates for groups A, B, and C were 13 (14.4% per patient and 8.3% per cycle), 28 (30.4% per patient and 19.4% per cycle), and 10 (10.9% per patient and 6.7% per cycle), respectively. There was a statistically significant difference between group B and groups A and C.\n Our data indicate that two IUIs performed 12 hours and 34 hours after hCG administration is the most cost-effective regimen for women undergoing COH cycles with clomiphene citrate and gonadotropins. Although the second insemination adds up to a slightly higher cost, it significantly increases the chance of pregnancy." ]

[ "6931470", "387151", "8104468", "406212", "3788652", "7032224", "3446307", "6349256", "2870944", "390972", "345313", "1681680" ]

[ "Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate.", "High dose flupenthixol decanoate in chronic schizophrenia.", "The decanoates of flupenthixol and clopenthixol in the treatment of chronic schizophrenic in-patients. Implications for community psychiatry.", "Clinical and social comparison of fluphenazine decanoate and flupenthixol decanoate in the community maintenance therapy of schizophrenia.", "Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison.", "A depot neuroleptic withdrawal study. A controlled study of the clinical effects of the withdrawal of depot fluphenazine decanoate and depot flupenthixol decanoate in chronic schizophrenic patients.", "Double-blind comparison of half-dose and standard-dose flupenthixol decanoate in the maintenance treatment of stabilised out-patients with schizophrenia.", "Comparative double-blind study of flupenthixol decanoate and fluphenazine decanoate in the treatment of patients relapsing in a schizophrenic symptomatology.", "A comparative trial of depot pipothiazine.", "A double-blind comparison of flupenthixol decanoate and fluphenazine decanoate in the treatment of chronic schizophrenia.", "A comparative controlled trial of pimozide and fluphenazine decanoate in the continuation therapy of schizophrenia.", "Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study." ]

[ "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.", "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.", "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.", "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.", "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.", "A double-blind withdrawal trial in 41 chronic schizophrenic outpatients on neuroleptics was carried out during 6 months. Long-acting neuroleptics (fluphenazine decanoate or flupenthixol decanoate) were used in comparison with placebo to determine the value in maintenance therapy. Most patients had a rather low maintenance dose, about 12.5-25 mg fluphenazine decanoate or 20-40 mg flupenthixol decanoate every third week. Relapse was often characterized by a return of the dame symptoms as the patient had during his first schizophrenic attack. Drugs were significantly more effective than placebo in preventing relapse and readmission to hospital. 62% relapsed in the placebo groups as compared with 27% in the drug group. All patients on active substance and without relapse during the controlled study had their treatment discontinued for 24 months in an open follow-up investigation. This resulted in relapse of all patients but one, i.e. a final relapse frequency of 97%. A significant weight decrease was observed in the placebo group. The risk of withdrawal is 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 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).", "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.", "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.", "Evidence from a controlled, comparative trial indicates that oral pimozide is clinically at least as effective as depot injections of fluphenazine decanoate in the continuation therapy of a group of schizophrenic patients discharged from hospital. The administration of pimozide was associated with fewer unwanted effects. The implications of the findings are discussed.", "Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals." ]

[ "16137351", "16227328", "10556125", "15065730", "18585831", "15065822", "20723631", "10859037", "16941367", "21281564", "17177928", "19654384", "12701945", "12460525", "8099639", "16882959", "15729064", "15236851" ]

[ "Intrapulmonary percussive ventilation in acute exacerbations of COPD patients with mild respiratory acidosis: a randomized controlled trial [ISRCTN17802078].", "Clinical efficacy of anti-pneumococcal vaccination in patients with COPD.", "Acute respiratory failure in patients with severe community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventilation.", "Improving physician coverage of pneumococcal vaccine: a randomized trial of a telephone intervention.", "Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease.", "Additive preventive effect of influenza and pneumococcal vaccines in elderly persons.", "Effectiveness of pneumococcal polysaccharide vaccine against pneumonia and cost analysis for the elderly who receive seasonal influenza vaccine in Japan.", "Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial.", "Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study.", "Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses.", "Adoption of a ventilator-associated pneumonia clinical practice guideline.", "Screening for intimate partner violence in health care settings: a randomized trial.", "Publication bias and meta-analyses: a practical example.", "Improving family physicians' use of evidence-based smoking cessation strategies: a cluster randomization trial.", "Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease.", "Approaches to screening for intimate partner violence in health care settings: a randomized trial.", "Survival benefit in critically ill burned patients receiving selective decontamination of the digestive tract: a randomized, placebo-controlled, double-blind trial.", "Reducing ventilator-associated pneumonia rates through a staff education programme." ]

[ "We hypothesized that the use of intrapulmonary percussive ventilation (IPV), a technique designed to improve mucus clearance, could prove effective in avoiding further deterioration in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) with mild respiratory acidosis.\n The study was performed in a medical intensive care unit of a university hospital. Thirty-three patients with exacerbations of COPD with a respiratory frequency >or= 25/min, a PaCO2 > 45 Torr and 7.35 <or= pH <or= 7.38 were included in the study. Patients were randomly assigned to receive either standard treatment (control group) or standard treatment plus IPV (IPV group). The IPV group underwent two daily sessions of 30 minutes performed by a chest physiotherapist through a full face mask. The therapy was considered successful when both worsening of the exacerbation and a decrease in pH to under 7.35, which would have required non-invasive ventilation, were avoided.\n Thirty minutes of IPV led to a significant decrease in respiratory rate, an increase in PaO2 and a decrease in PaCO2 (p < 0.05). Exacerbation worsened in 6 out of 17 patients in the control group versus 0 out of 16 in the IPV group (p < 0.05). The hospital stay was significantly shorter in the IPV group than in the control group (6.8 +/- 1.0 vs. 7.9 +/- 1.3 days, p < 0.05).\n IPV is a safe technique and may prevent further deterioration in patients with acute exacerbations of COPD with mild respiratory acidosis.", "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.", "In uncontrolled studies, noninvasive positive pressure ventilation (NPPV) was found useful in avoiding endotracheal intubation in patients with acute respiratory failure (ARF) caused by severe community-acquired pneumonia (CAP). We conducted a prospective, randomized study comparing standard treatment plus NPPV delivered through a face mask to standard treatment alone in patients with severe CAP and ARF. Patients fitting the American Thoracic Society criteria for severe CAP were included in presence of ARF (refractory hypoxemia and/or hypercapnia with acidosis). Exclusion criteria were: severe hemodynamic instability, requirement for emergent cardiopulmonary resuscitation, home mechanical ventilation or oxygen long-term supplementation, concomitant severe disease with a low expectation of life, inability to expectorate or contraindications to the use of the mask. Fifty-six consecutive patients (28 in each arm) were enrolled, and the two groups were similar at study entry. The use of NPPV was well tolerated, safe, and associated with a significant reduction in respiratory rate, need for endotracheal intubation (21% versus 50%; p = 0.03), and duration of intensive care unit (ICU) stay (1.8 +/- 0.7 d versus 6 +/- 1.8 d; p = 0.04). The two groups had a similar intensity of nursing care workload, time interval from study entry to endotracheal intubation, duration of hospitalization, and hospital mortality. Among patients with chronic obstructive pulmonary disease (COPD), those randomized to NPPV had a lower intensity of nursing care workload (p = 0.04) and improved 2-mo survival (88.9% versus 37.5%; p = 0.05). We conclude that in selected patients with ARF caused by severe CAP, NPPV was associated with a significant reduction in the rate of endotracheal intubation and duration of ICU stay. A 2-mo survival advantage was seen in patients with COPD.", "Improved pneumococcal vaccine (PPV) immunization for seniors is a national goal of the Medicare program. This study examined whether adding a simple telephone follow-up to an existing mailed physician performance feedback under the Medicare program would increase the impact on billed pneumococcal immunizations. Medicare fee-for-service claims data were used to select New York primary care physicians with high volume (n = 732) or African-American serving (n = 329) practices. All practices received mailed feedback on their 1999 Medicare practice specific PPV coverage rates, along with educational materials and offers of assistance. Practices were also randomized to receive telephone calls directing attention to the mailing and further promoting improvements in PPV coverage or no active follow-up. Physicians randomized to telephone follow-up showed significantly higher rates of practice specific PPV coverage in 2000 than those receiving the routine mailing only, and 27% vs. 17% (p = 0.01) of high volume physicians and 34% vs. 22% (p = .052) of African American serving physicians achieved at least a 5% increase in their cumulative PPV claims coverage. This study concludes that telephone follow-up is an effective and straightforward method to enhance the impact of practice specific feedback to promote improvements in Medicare PPV immunization. However, improved methods may be needed to induce a large percentage of physicians to change.", "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.", "In 1999, all individuals > or = 65 yrs of age (n=258,754) in Stockholm County, Sweden, were offered influenza and pneumococcal vaccination in a prospective study on the effectiveness of these vaccines in reducing the need for hospital treatment and death due to influenza, pneumonia and invasive pneumococcal disease (IPD). Data on hospitalisation and mortality during 1 yr were obtained from the administrative database in Stockholm County Council. Vaccination was performed in 124,702 (48%) subjects; 72,107 had both vaccines, 29,346 only had the influenza vaccine and 23,249 only had the pneumococcal vaccine. Compared with the unvaccinated cohort, a lower incidence of hospitalisation for all endpoint diagnoses was seen in vaccinated persons. An additive effectiveness of vaccination was seen when both vaccines were given, with a reduction of hospital admissions for influenza (37%), pneumonia (29%) and IPD (44%). In-hospital mortality for pneumonia was significantly lower in those who received both vaccines, than in unvaccinated persons. To conclude, vaccination with influenza and pneumococcal vaccines together was effective in reducing the need for hospital admission for influenza and pneumonia. There was a strong indication that pneumococcal vaccination alone, was effective not only in the prevention of invasive pneumococcal disease, but also of pneumonia overall, although to a low degree.", "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.", "Within the intensive-care unit, non-invasive ventilation (NIV) can prevent the need for intubation and the mortality associated with severe episodes of chronic obstructive pulmonary disease (COPD). The aim of this study was to find whether the introduction of NIV, early after the admission on a general respiratory ward, was effective at reducing the need for intubation and the mortality associated with acute exacerbations of COPD.\n We did a prospective multicentre randomised controlled study comparing NIV with standard therapy in patients with mild to moderate acidosis. NIV was administered on the ward with a simple non-invasive ventilator and a standardised predefined protocol. Patients were recruited from 14 UK hospitals over 22 months.\n 236 patients were recruited, 118 received standard therapy alone and 118 additional NIV. The two groups had similar characteristics at enrolment. The use of NIV significantly reduced the need for intubation as defined by the failure criteria. 32/118 (27%) of the standard group failed compared with 18/118 (15%) of the NIV group (p=0.02). In-hospital mortality was also reduced by NIV, 24/118 (20%) died in the standard group compared with 12/118 (10%) in the NIV group (p=0.05). In both groups pH, PaCO2, and respiratory rate improved at 4 h (p<0.01). However, NIV led to a more rapid improvement in pH in the first hour (p=0.02) and a greater fall in respiratory rate at 4 h (p=0.035). The duration of breathlessness was also reduced by NIV (p=0.025).\n The early use of NIV for mildly and moderately acidotic patients with COPD in the general ward setting leads to more rapid improvement of physiological variables, a reduction in the need for invasive mechanical ventilation (with objective criteria), and a reduction in in-hospital mortality.", "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.", "Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in infants and young children and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). Palivizumab (Synagis®, MedImmune) is a monoclonal antibody designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection. It is licensed for the prevention of serious lower respiratory tract infection caused by RSV in children at high risk. While it is recognised that a policy of using palivizumab for all children who meet the licensed indication does not meet conventional UK standards of cost-effectiveness, most clinicians feel that its use is justified in some children.\n To use systematic review evidence to estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of children with or without CLD or CHD who are at high risk of serious morbidity from RSV infection.\n A systematic review of the literature and an economic evaluation was carried out. The bibliographic databases included the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] and five other databases, from inception to 2009. Research registries of ongoing trials including Current Controlled Trials metaRegister, Clinical Trials.gov and the National Institute for Health Research Clinical Research Network Portfolio were also searched.\n Searches were conducted for prognostic and hospitalisation studies covering 1950-2009 (the original report searches conducted in 2007 covering the period 1950-2007 were rerun in August 2009 to cover the period 2007-9) and the database of all references from the original report was sifted to find any relevant studies that may have been missed. The risk factors identified from the systematic review of included studies were analysed and synthesised using stata. The base-case decision tree model developed in the original HTA journal publication [Health Technol Assess 2008;12(36)] was used to derive the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of pre-term infants and young children who are at high risk of serious morbidity from RSV infection. Cost-effective spectra of prophylaxis with palivizumab compared with no prophylaxis for children without CLD/CHD, children with CLD, children with acyanotic CHD and children with cyanotic CHD were derived.\n Thirteen studies were included in this analysis. Analysis of 16,128 subgroups showed that prophylaxis with palivizumab may be cost-effective [at a willingness-to-pay threshold of £30,000/quality-adjusted life-year (QALY)] for some subgroups. For example, for children without CLD or CHD, the cost-effective subgroups included children under 6 weeks old at the start of the RSV season who had at least two other risk factors that were considered in this report and were born at 24 weeks gestational age (GA) or less, but did not include children who were > 9 months old at the start of the RSV season or had a GA of > 32 weeks. For children with CLD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 28 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with acyanotic CHD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with cyanotic CHD, the cost-effective subgroups included children < 6 weeks old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 12 months old at the start of the RSV season.\n The poor quality of the studies feeding numerical results into this analysis means that the true cost-effectiveness may vary considerably from that estimated here. There is a risk that the relatively high mathematical precision of the point estimates of cost-effectiveness may be quite inaccurate because of poor-quality inputs.\n Prophylaxis with palivizumab does not represent good value for money based on the current UK incremental cost-effectiveness ratio threshold of £30,000/QALY when used unselectively in children without CLD/CHD or children with CLD or CHD. This subgroup analysis showed that prophylaxis with palivizumab may be cost-effective (at a willingness-to-pay threshold of £30,000/QALY) for some subgroups. In summary, the cost-effective subgroups for children who had no CLD or CHD must contain at least two other risk factors apart from GA and birth age. The cost-effective subgroups for children who had CLD or CHD do not necessarily need to have any other risk factors. Future research should be directed towards conducting much larger, better powered and better reported studies to derive better estimates of the risk factor effect sizes.\n This report was funded by the HTA programme of the National Institute for Health Research.", "The Academic Center for Evidence-based Practice (ACE) Star Model was used to implement an evidence-based clinical practice guideline (CPG) in order to decrease ventilator-associated pneumonia (VAP) incidence rates and ventilator days. The goal was to interrupt person-to-person transmission of bacteria and bacterial colonization using low-cost, evidence-based strategies to prevent VAP. DISCOVERY: Two geographically proximate medical centers, inclusive of five intensive care units located in the southwestern region of the United States had significant variations in their VAP rates.\n Using the U.S. Preventive Services Task Force grading criteria, the results of 69 studies were used to establish a clinical practice guideline to prevent ventilator-associated pneumonia. TRANSLATION: A clinical practice guideline was developed for the prevention of VAP and included five nursing activities: (a) head-of-bed elevation; (b) oral care; (c) ventilator tubing condensate removal; (d) hand hygiene; and (e) glove use. The effect of the CPG, inclusive of an educational intervention, was measured using an observational, prospective, quasi-experimental design. INTEGRATION: A multidisciplinary education team developed a self-learning packet, educational materials, and storyboards for the staff as dissemination strategies. Strategies also included e-mail, one-on-one teaching with clinicians, and feedback on guideline adoption and VAP rate reports.\n Observation data were collected to evaluate adoption of the CPG while caring for 106 ventilated patients. VAP rates changed at both hospitals although the change was not statistically significant. Additionally, the ICU length of stay declined at both facilities, causing cost savings.\n These results support the idea that adoption of evidence-based practices contributes to decreased VAP rates. For a successful program, ICU leaders should emphasize strategies that routinize adoption of evidence-based CPGs.", "Whether intimate partner violence (IPV) screening reduces violence or improves health outcomes for women is unknown.\n To determine the effectiveness of IPV screening and communication of positive results to clinicians.\n Randomized controlled trial conducted in 11 emergency departments, 12 family practices, and 3 obstetrics/gynecology clinics in Ontario, Canada, among 6743 English-speaking female patients aged 18 to 64 years who presented between July 2005 and December 2006, could be seen individually, and were well enough to participate.\n Women in the screened group (n=3271) self-completed the Woman Abuse Screening Tool (WAST); if a woman screened positive, this information was given to her clinician before the health care visit. Subsequent discussions and/or referrals were at the discretion of the treating clinician. The nonscreened group (n=3472) self-completed the WAST and other measures after their visit.\n Women disclosing past-year IPV were interviewed at baseline and every 6 months until 18 months regarding IPV reexposure and quality of life (primary outcomes), as well as several health outcomes and potential harms of screening.\n Participant loss to follow-up was high: 43% (148/347) of screened women and 41% (148/360) of nonscreened women. At 18 months (n = 411), observed recurrence of IPV among screened vs nonscreened women was 46% vs 53% (modeled odds ratio, 0.82; 95% confidence interval, 0.32-2.12). Screened vs nonscreened women exhibited about a 0.2-SD greater improvement in quality-of-life scores (modeled score difference at 18 months, 3.74; 95% confidence interval, 0.47-7.00). When multiple imputation was used to account for sample loss, differences between groups were reduced and quality-of-life differences were no longer significant. Screened women reported no harms of screening.\n Although sample attrition urges cautious interpretation, the results of this trial do not provide sufficient evidence to support IPV screening in health care settings. Evaluation of services for women after identification of IPV remains a priority.\n clinicaltrials.gov Identifier: NCT00182468.", "Publication bias is widely appreciated, but considerable time and effort are needed to locate and obtain data from unpublished randomized controlled trials (RCTs), those published in non-English language journals or those reported in the gray literature; for this publication, we will call this collection of trials the \"gray+literature.\" However, excluding such trials from systematic reviews could introduce bias and give rise to misleading conclusions.\n We aimed to explore and quantify the impact of inclusion of gray+ literature on the results of all completed individual patient data (IPD) reviews coordinated by our group (13 meta-analyses). For each IPD review, results were calculated for RCTs fully published in English language journals and RCTs fully published in English language journals and the gray+literature.\n The IPD meta-analyses based only on RCTs that were fully published in English language journals tended to give more favorable results than those that included RCTs from the gray+literature. Although in most cases the addition of gray+data gave less encouraging results, moving the estimated treatment effect toward a null result, the direction of effect was not always predictable.\n We recommend that all systematic reviews should at least attempt to identify trials reported in the gray+literature and, where possible, obtain data from them.", "Family physicians (FPs) in Australia underutilize effective strategies to help patients stop smoking. We conducted a cluster randomization trial to evaluate a multifaceted, practice-based intervention involving audit, feedback, and academic detailing to improve FP smoking cessation advice.\n Sixty FPs in 39 practices participated. FPs' provision of smoking cessation advice was measured by patient recall, medical record audit, and FP self-report. Logistic regression analysis using generalized estimating equations was performed to assess improvements in practice, after adjustment for clustering by practice.\n Improvements between baseline and posttest in patient recall of FP advice about nicotine replacement patches and gum were significantly greater in the intervention than in the control group (P = 0.0056 and P = 0.0002, respectively). While there were substantial increases in patient recall of assessment of smoking status and FP use of \"quit dates,\" behavioral advice, and written materials in the intervention group, these changes were not significantly greater than those in the control group. Notation of patients' smoking status and smoking cessation advice in medical records remained suboptimal in both groups.\n This multifaceted intervention was successful only in promoting FPs' use of nicotine replacement therapy. While the use of other effective cessation strategies appeared to increase, a larger trial is needed for further evaluation.", "Acute exacerbations of chronic obstructive airways disease (COAD) are a common cause of admission to hospital, and have a high mortality. Nasal intermittent positive pressure ventilation (NIPPV) has been used successfully in patients with respiratory failure due to neuromuscular and skeletal disorders, but the outcome of treatment in patients with COAD is less well known. We carried out a prospective randomised controlled trial of conventional treatment versus conventional treatment plus NIPPV, in 60 patients with acute ventilatory failure due to exacerbations of COAD. For the NIPPV group there was a rise in pH, compared with a fall in the controls (mean difference of change between the groups 0.046 [95% CI 0.06-0.02, p < 0.001]), and a larger fall in PaCO2 (mean difference in change between the groups 1.2 kPa [95% CI 0.45 to 2.03, p < 0.01]). Median visual analogue scores over the first 3 days of admission showed less breathlessness in the NIPPV group (2.3 cm [range 0.1-5.5]) than in the control group (4.5 cm [range 0.9-8.8]) (p < 0.025). Survival rates at 30 days were compared for intention-to-treat and efficacy populations. In the efficacy mortality comparison, mortality in the NIPPV group was reduced: 1/26 vs 9/30 (relative risk = 0.13, CI = 0.02-0.95, p = 0.014). This effect was less in the intention-to-treat analysis: 3/30 vs 9/30 (relative risk = 0.33, CI = 0.10-1.11, p = 0.106). In patients with acute ventilatory failure due to COAD who received NIPPV there was a significant rise in pH, a reduction in PaCO2 and breathlessness, and reduced mortality.", "Screening for intimate partner violence (IPV) in health care settings has been recommended by some professional organizations, although there is limited information regarding the accuracy, acceptability, and completeness of different screening methods and instruments.\n To determine the optimal method for IPV screening in health care settings.\n Cluster randomized trial conducted from May 2004 to January 2005 at 2 each of emergency departments, family practices, and women's health clinics in Ontario, Canada.\n English-speaking women aged 18 to 64 years who were well enough to participate and could be seen individually were eligible. Of 2602 eligible women, 141 (5%) refused participation.\n Participants were randomized by clinic day or shift to 1 of 3 screening approaches: a face-to-face interview with a health care provider (physician or nurse), written self-completed questionnaire, and computer-based self-completed questionnaire. Two screening instruments-the Partner Violence Screen (PVS) and the Woman Abuse Screening Tool (WAST)-were administered and compared with the Composite Abuse Scale (CAS) as the criterion standard.\n The approaches were evaluated on prevalence, extent of missing data, and participant preference. Agreement between the screening instruments and the CAS was examined.\n The 12-month prevalence of IPV ranged from 4.1% to 17.7%, depending on screening method, instrument, and health care setting. Although no statistically significant main effects on prevalence were found for method or screening instrument, a significant interaction between method and instrument was found: prevalence was lower on the written WAST vs other combinations. The face-to-face approach was least preferred by participants. The WAST and the written format yielded significantly less missing data than the PVS and other methods. The PVS and WAST had similar sensitivities (49.2% and 47.0%, respectively) and specificities (93.7% and 95.6%, respectively).\n In screening for IPV, women preferred self-completed approaches over face-to-face questioning; computer-based screening did not increase prevalence; and written screens had fewest missing data. These are important considerations for both clinical and research efforts in IPV screening.\n clinicaltrials.gov Identifier: NCT00336297.", "To evaluate whether selective digestive decontamination (SDD) reduces mortality from any cause, and the incidence of pneumonia among patients with severe burns.\n SDD is a prophylactic strategy to reduce infectious morbidity and mortality in critically ill patients. Two meta-analyses and a recent randomized controlled trial demonstrated a mortality reduction varying between 20% and 40%. But this technique has never been properly evaluated in severely burned patients.\n The design of this single-center trial was randomized, double blind, placebo controlled. Patients with burns > or =20% of total body surface and/or suspected inhalation injury were enrolled and assigned to receive SDD or placebo for the total duration of treatment in the burn intensive care unit (ICU).\n One hundred seventeen patients were randomized and 107 were analyzed (53 in the SDD group and 54 in the placebo group). The ICU mortality was 27.8% in the placebo group and 9.4% in the SDD group in the burn ICU. Treatment with SDD was associated with a significant reduction in mortality both in the burn ICU (risk ratio 0.25; 95% CI 0.08 to 0.76) and in the hospital (risk ratio 0.28; 95% CI 0.10 to 0.80), following adjustment for predicted mortality. The incidence of pneumonia was significantly higher in the placebo group: 30.8 and 17.0 pneumonias per 1000 ventilation days (P = 0.03) in placebo and SDD group, respectively.\n Treatment with SDD reduces mortality and pneumonia incidence in patients with severe burns.", "Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in patients on mechanical ventilation and results in increases in mortality, prolonged hospitalization and costs. Preventive measures for VAP are well-documented and evidence-based, yet remain poorly implemented in most intensive care units. We undertook an observational pre and post-intervention study to assess whether an educational programme focusing on preventive practices for VAP could reduce the incidence. Six hundred and seventy-seven adult patients, mechanically ventilated for >48 h were included in the study population. An evidence-based guideline for preventive practices at the bedside was developed and disseminated to the intensive care unit staff. VAP incidence rates before and after implementation of the educational programme were compared. VAP infection rates reduced by 51%, from a mean of 13.2+/-1.2 in the pre-intervention period to 6.5+/-1.5/1000 device days in the post-intervention period (mean difference 6.7; 95% CI: 2.9-10.4, P =0.02). A multidisciplinary educational programme geared towards intensive care unit staff can successfully reduce the incidence rates of VAP. Further studies will be needed to assess the impact on broader outcome measures such as costs or mortality." ]

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[ "Occlusal caries prevention in high and low risk schoolchildren. A clinical trial.", "Clinical effectiveness of an autopolymerized fissure sealant after 2 years.", "Evaluation of non-invasive treatment applied to occlusal surfaces.", "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.", "Caries-preventive effect of sealants produced with altered glass-ionomer materials, after 2 years.", "Sealant and fluoride varnish in caries: a randomized trial.", "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.", "Randomized trial on fluorides and sealants for fissure caries prevention.", "Effectiveness of a glass ionomer cement used as a pit and fissure sealant in recently erupted permanent first molars.", "Clinical evaluation of glass-ionomer/resin-based hybrid materials used as pit and fissure sealants.", "Clinical success and potential failure after single application of a pit and fissure sealant: a four-year report.", "Retention of a glass ionomer cement and a resin-based fissure sealant and effect on carious outcome after 7 years.", "Clinical evaluation of three different materials used as pit and fissure sealant: 24-months results.", "Caries-preventive effect of a one-time application of composite resin and glass ionomer sealants after 5 years.", "Clinical and antibacterial effectiveness of three different sealant materials.", "A comparison of retention and the effect on caries of fissure sealing with a glass-ionomer and a resin-based sealant.", "Fissure sealing with a light-cured resin-reinforced glass-ionomer cement (Vitrebond) compared with a resin sealant.", "A 24-month study comparing sealant and fluoride varnish in caries reduction on different permanent first molar surfaces.", "A comparative study of fluoride-releasing composite resin and glass ionomer materials used as fissure sealants.", "Fissure sealing of permanent first molars in children receiving a high standard of prophylactic care.", "Caries preventive effect of a fluoride-containing varnish (Duraphat) after 1 year's study.", "Evaluation of resin based and glass ionomer based sealants placed with or without tooth preparation-a two year clinical trial.", "Effects of glass ionomer cement, resin-based pit and fissure sealant and HF applications on occlusal caries in a developing country field trial.", "The effectiveness of a chemically polymerized sealant in preventing occlusal caries: two year results.", "[Caries prevention by means of a Na2FPO3-toothpaste after 7 year's application].", "Clinical evaluation of a polyacid-modified resin composite-based fissure sealant: two-year results.", "The caries-preventive effect of a fluoride varnish in the fissures of the first permanent molar.", "Clinical evaluation of FUJI VII sealant material.", "Noninvasive control of dental caries in children with active initial lesions. A randomized clinical trial.", "Three-year study of the effect of fluoride varnish (Duraphat) on proximal caries progression in teenagers.", "Observations on dental caries in primary teeth after frequent fluoride toplications in a program involving other preventives.", "Three-year caries increments after fluoride rinses or topical applications with a fluoride varnish." ]

[ "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.", "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.", "The purpose of this study was to evaluate the efficacy of non-invasive methods of treatment for active incipent occlusal caries. Anamnesis, professional prophylaxis, and visual inspection were used to classify 250 Brazilian pre-school-children. First permanent decayed molars (n=98) from thirty-one subjects (6 years+ 6 months) were selected and divided into three groups. Group 1: fissure sealants with resin-modified glass ionomer - Vitremer (n=29); Group 2: fluoride varnish -Duraphat (n=36) and control group: tooth brushing and 0.2 percent NaF weekly mouthwashes (n=33). Four clinical evaluations were carried out over three, six, nine, and twelve months. Caries activity and progression were observed through clinical and radiographic evaluation. The results were analyzed by Fisher=s Exact test. After twelve months, the results showed 100 percent of arrestment of caries activity for Group 1, 83.3 percent for group 2, and 72.7 percent for control group. At the same time, the results showed 0 percent of caries progression for group 1, 5.5 percent for Group 2, and 6.1 percent for control group. Group 1 showed a better inactivation property than the other groups (p<0.05). There were no statistically significant differences in caries progression among these groups (p>0.05). It was concluded that this non-invasive methods were able to arrest the progression of occlusal caries, but fissure sealant showed better results in controlling caries activity.", "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 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.", "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 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.", "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).", "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.", "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 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.", "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 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.", "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 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.", "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.", "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 aim of this study was to determine the separate effects of dental sealants and fluoride varnish on dental caries in fissured and nonfissured surfaces of permanent first molars.\n A clinical trial was conducted with three groups of 6- to 8-year-old schoolchildren: a sealant group (n = 100), in which Delton was applied to first molars; a varnish group (n = 98), in which Duraphat was applied to first molars; and a control group (n = 116), which had no intervention as part of the study. Absolute and percent caries reductions were compared at 24 months.\n Compared to the controls, sealants resulted in a 68 percent and 87 percent reduction on fissured and nonfissured surfaces, respectively. The corresponding figures for varnish were 38 percent and 66 percent.\n Sealant and fluoride varnish are effective in preventing caries in both fissured and nonfissured surface.", "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.", "The efficiency of sealing the occlusal fissures of permanent first molars was studied in a group of patients 6-9 yr of age receiving a high standard of prophylactic care. Very soon after the eruption one of the teeth in a homomaxillary pair was sealed, and the contralateral was used for control. The control teeth were painted with a fluoride varnish (Duraphat) every 6 months during the trial. 210 sites in 121 children were sealed and followed for a mean observation period of 23 months. At the end of the study, the retention rate was 62.9%, the percentage of effectiveness 24.2%, and the net gain 7.1%. The dmft index (primary molars and canines) was recorded for each patient at the time sealing was performed. A relationship between the caries prevalence in the primary teeth and the susceptibility for fissure caries in the control teeth was found. Effectiveness and net gain was highest in the group of children with 3-6 dmft.", "The caries prophylactic effect of semi-annual applications of a fluoride-containing varnish (Duraphat) was tested in 121 15-year-old children. The children were divided into a test (60 subjects). The teeth of the children in the test group were coated with fluoride varnish at the beginning of the experimental period and again 6 months later. A clinical and radiographic examination of all children was performed immediately prior to the first application of varnish and 1 year later. The mean caries increment was 0.9 new DMFS in the test group and 4.0 in the control group. The difference was statistically significant at the 0.1% level. The caries prophylactic effect on different tooth surfaces was statistically significant both on proximal and on occlusal surfaces at the 0.1% level. Analyzing the material with respect to the caries prophylactic effect against the background of caries prevalence at the start of the investigation showed a better effect in the group of children with low and medium initial DMFS values.", "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.", "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", "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%.", "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.", "The aim of the present study was to assess the caries-preventive effect of topical application of Duraphat on the occlusal surface of newly erupted first permanent molars. A base-line examination was performed on children aged 5 years and 9 months. The children were randomly divided into a Duraphat group and a control group. In accordance with the anatomy of the fissure system, the molars were divided into shallow and deep fissures, respectively. From the time of eruption, 381 molars were examined every 3rd month during 24 months. Duraphat was applied every 6th month, altogether four times. The results showed that in the Duraphat group 35% of the fissures were decayed compared with 80% in the control group. Caries reduction amounted to 56%, and the caries-preventive effect was found in molars with shallow and deep fissures.", "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.", "The aim of this study was to investigate whether DMFS increment can be decreased among children with active initial caries by oral hygiene and dietary counseling and by using noninvasive preventive measures. Except for mentally disabled and handicapped children attending special schools, all 11- to 12-year-olds in Pori, Finland, with at least one active initial caries lesion were invited to participate in the study and were then randomized into two groups. Children in the experimental group (n = 250) were offered an individually designed patient-centered preventive program aimed at identifying and eliminating factors that had led to the presence of active caries. The program included counseling sessions with emphasis on enhancing use of the children's own resources in everyday life. Toothbrushes, fluoride toothpaste and fluoride and xylitol lozenges were distributed to the children. They also received applications of fluoride/chlorhexidine varnish. The children in the control group (n = 247) received basic prevention offered as standard in the public dental clinics in Pori. For both groups, the average follow-up period was 3.4 years. A community level program of oral health promotion was run in Pori throughout this period. Mean DMFS increments for the experimental and control groups were 2.56 (95% CI 2.07, 3.05) and 4.60 (3.99, 5.21), respectively (p < 0.0001): prevented fraction 44.3% (30.2%, 56.4%). The results show that by using a regimen that includes multiple measures for preventing dental decay, caries increment can be significantly reduced among caries-active children living in an area where the overall level of caries experience is low.\n 2007 S. Karger AG, Basel", "The effect of sodium fluoride varnish (Duraphat) applications on proximal caries progression was studied during a 3-yr period in 87 teenagers and compared to a control group (n = 107). In the fluoride varnish group the children were treated with fluoride varnish every third month during the experimental period. Caries lesions on the mesial surfaces of first premolars to the mesial surfaces of second molars were recorded annually on radiographs and an individual progression value was calculated. The study showed that topical application of fluoride varnish every third month significantly (P less than 0.05) reduced the progression of proximal caries lesions in premolars and molars. The most obvious reduction of caries progression was observed among children who developed between two and eight new proximal lesions during the test period. In the children with the highest caries activity (greater than nine new proximal lesions) Duraphat treatments did not significantly reduce proximal caries progression in premolars and molars.", "The anticaries effect of repeated toplications with APF gel was assessed in the primary dentition of 2-6-year-olds after 8, 18 and 28 months. Frequent, but less than daily, topical fluoride therapy appeared to have little effect in pre-school children consuming water-borne fluoride and receiving other traditionally recommended modalities of prevention.", "251 9-12-yr-old children completed a 3-yr, double-blind, clinical trial of two caries preventive fluoride programs. Caries increments and progression patterns were compared in two groups of children who rinsed every fortnight with a 0.2% NaF solution or received biannual topical applications with a fluoride varnish (Fluor-Protector). Clinically recorded mean DFS increments were 3.3 +/- 0.2 (SE) in the rinse group and 3.5 +/- 0.2 in the varnish group. In both groups nearly half of these increments were recorded in the occlusal surfaces of second molars. The mean incremental DFS recorded radiographically on approximal surfaces of posterior teeth were 1.1 +/- 0.2 and 1.5 +/- 0.2 in the rinse and varnish group, respectively. None of the inter-group differences were statistically significant (P greater than 0.05). Detailed analyses of the radiographic scores revealed a similar and extremely slow caries progression in the two study groups and they strengthened the conclusion of equal clinical efficacy of the two treatments. None of the fluoride programs had been able to change preestablished patterns of caries development among the children." ]

[ "17473138", "9450711", "9723823", "9310565" ]

[ "Commercially funded and United States-based research is more likely to be published; good-quality studies with negative outcomes are not.", "Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials.", "Bias in reporting clinical trials.", "Publication bias: evidence of delayed publication in a cohort study of clinical research projects." ]

[ "Prior studies implying associations between receipt of commercial funding and positive (significant and/or pro-industry) research outcomes have analyzed only published papers, which is an insufficiently robust approach for assessing publication bias. In this study, we tested the following hypotheses regarding orthopaedic manuscripts submitted for review: (1) nonscientific variables, including receipt of commercial funding, affect the likelihood that a peer-reviewed submission will conclude with a report of a positive study outcome, and (2) positive outcomes and other, nonscientific variables are associated with acceptance for publication.\n All manuscripts about hip or knee arthroplasty that were submitted to The Journal of Bone and Joint Surgery, American Volume, over seventeen months were evaluated to determine the study design, quality, and outcome. Analyses were carried out to identify associations between scientific factors (sample size, study quality, and level of evidence) and study outcome as well as between non-scientific factors (funding source and country of origin) and study outcome. Analyses were also performed to determine whether outcome, scientific factors, or nonscientific variables were associated with acceptance for publication.\n Two hundred and nine manuscripts were reviewed. Commercial funding was not found to be associated with a positive study outcome (p = 0.668). Studies with a positive outcome were no more likely to be published than were those with a negative outcome (p = 0.410). Studies with a negative outcome were of higher quality (p = 0.003) and included larger sample sizes (p = 0.05). Commercially funded (p = 0.027) and United States-based (p = 0.020) studies were more likely to be published, even though those studies were not associated with higher quality, larger sample sizes, or lower levels of evidence (p = 0.24 to 0.79).\n Commercially funded studies submitted for review were not more likely to conclude with a positive outcome than were nonfunded studies, and studies with a positive outcome were no more likely to be published than were studies with a negative outcome. These findings contradict those of most previous analyses of published (rather than submitted) research. Commercial funding and the country of origin predict publication following peer review beyond what would be expected on the basis of study quality. Studies with a negative outcome, although seemingly superior in quality, fared no better than studies with a positive outcome in the peer-review process; this may result in inflation of apparent treatment effects when the published literature is subjected to meta-analysis.", "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.", "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.", "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." ]

[ "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." ]

[ "11477970", "8571154", "8356485", "12973646", "10155878", "15686063", "15746218", "1958910", "12017833", "12135994", "10151841", "1354792", "18237352", "10662412" ]

[ "Effect of removing user fees on attendance for curative and preventive primary health care services in rural South Africa.", "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.", "Fees-for-services, cost recovery, and equity in a district of Burkina Faso operating the Bamako Initiative.", "The fall and rise of cost sharing in Kenya: the impact of phased implementation.", "The impact of user fee exemption on service utilization and treatment seeking behaviour: the case of malaria in Sudan.", "Abolition of cost-sharing is pro-poor: evidence from Uganda.", "Online access to MEDLINE in clinical settings: impact of user fees.", "User charges and utilisation of obstetric services in the National Capital District, Papua New Guinea.", "The impact of price changes on demand for family planning and reproductive health services in Ecuador.", "The impact of alternative cost recovery schemes on access and equity in Niger.", "Impact of user fees on attendance at a referral centre for sexually transmitted diseases in Kenya.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "The effect of a copay increase on pharmaceutical utilization, expenditures, and treatment continuation." ]

[ "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.", "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.", "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.", "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.", "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.", "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 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.", "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.", "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.", "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.", "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.", "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation.", "No research has evaluated the impact of an increase to a copay that is reflective of today's healthcare market. This study examined the effect of an increase from a $10 to $15 copay for brand drugs on key pharmaceutical utilization measures, including participation rates, treatment continuation, and expenditures, in an adult population.\n A quasi-experimental, pre-post design with control group was used.\n Two different employer plans implemented an increase from $10 to $15 for brand copays in January of 1997. The utilization and expenditures of these plans were compared with those of a control group with a constant brand copay of $10 for 6 months preceding and 6 months following the copay increase.\n When other predictor variables were controlled for, the copay increase was not associated with a statistically significant difference in overall utilization compared with the control group, although brand utilization was significantly lower in the copay group. Savings to the payer were substantial, and resulted primarily from cost-shifting, reduction in brand utilization, and an increase in the generic fill rate. The rates of continuation with chronic medications in the 6 months following the copay increase were not reduced in the copay group compared with the control group.\n A copay increase can provide substantial savings to a payer without being a major deterrent to overall utilization or resulting in discontinuation of chronic medications." ]

[ "14872039", "10487186" ]

[ "Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study.", "Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents." ]

[ "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.", "Antiepileptic drugs (AEDs) are potential teratogenic agents. The purpose of this study was to examine the long-term effects of intrauterine AED exposure on neurologic and psychological functioning.\n Of a prospective study, \"Epilepsy, pregnancy, and child development,\" children could be retraced at school age and adolescence. Sixty-seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects.\n Type of maternal epilepsy and type and kind of AED therapy, but not maternal seizures during pregnancy correlated with an increase in abnormal EEG patterns. Minor neurologic dysfunction was diagnosed, with increased frequency from the control to the risk/no drug or monotherapy to the polytherapy group. The compromised intelligence score of the polytherapy group was primarily due to those children who had been exposed to primidone (PRM). Level of IQ was negatively associated with PRM dosage.\n Maternal epilepsy and AED therapy during pregnancy appear to have long-term effects on the offspring well into adolescence, as evinced in EEG patterns, minor neurologic dysfunction, and intellectual performance. Severity of effects increased from control group to epilepsy/no-drug group to monotherapy group and was most marked in the polytherapy group. These group differences are assumed to reflect differential neural vulnerability to social and family factors." ]

[ "17568029" ]

[ "A multicenter, randomized trial of prophylactic fluconazole in preterm neonates." ]

[ "Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates.\n During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing.\n Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P<0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant candida species was observed, but the study did not have substantial power to detect such an effect.\n Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).\n Copyright 2007 Massachusetts Medical Society." ]

[ "16084925", "12694632", "16708003", "22032247", "18237352" ]

[ "Can a facilitated programme promote effective multidisciplinary audit in secondary care teams? An exploratory trial.", "Randomised controlled trial of a theoretically grounded tailored intervention to diffuse evidence-based public health practice [ISRCTN23257060].", "Cluster randomized controlled trial of the effectiveness of audit and feedback and educational outreach on improving nursing practice and patient outcomes.", "Implementing collaborative care for depression treatment in primary care: a cluster randomized evaluation of a quality improvement practice redesign.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews." ]

[ "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.", "Previous studies have shown that Norwegian public health physicians do not systematically and explicitly use scientific evidence in their practice. They work in an environment that does not encourage the integration of this information in decision-making. In this study we investigate whether a theoretically grounded tailored intervention to diffuse evidence-based public health practice increases the physicians' use of research information.\n 148 self-selected public health physicians were randomised to an intervention group (n = 73) and a control group (n = 75). The intervention group received a multifaceted intervention while the control group received a letter declaring that they had access to library services. Baseline assessments before the intervention and post-testing immediately at the end of a 1.5-year intervention period were conducted. The intervention was theoretically based and consisted of a workshop in evidence-based public health, a newsletter, access to a specially designed information service, to relevant databases, and to an electronic discussion list. The main outcome measure was behaviour as measured by the use of research in different documents.\n The intervention did not demonstrate any evidence of effects on the objective behaviour outcomes. We found, however, a statistical significant difference between the two groups for both knowledge scores: Mean difference of 0.4 (95% CI: 0.2-0.6) in the score for knowledge about EBM-resources and mean difference of 0.2 (95% CI: 0.0-0.3) in the score for conceptual knowledge of importance for critical appraisal. There were no statistical significant differences in attitude-, self-efficacy-, decision-to-adopt- or job-satisfaction scales. There were no significant differences in Cochrane library searching after controlling for baseline values and characteristics.\n Though demonstrating effect on knowledge the study failed to provide support for the hypothesis that a theory-based multifaceted intervention targeted at identified barriers will change professional behaviour.", "Current understanding of implementation methods is limited, and research has focused on changing doctors' behaviors.\n Our aim was to evaluate the impact of audit and feedback and educational outreach in improving nursing practice and patient outcomes.\n Using a factorial design, cluster randomized controlled trial, we evaluated 194 community nurses in 157 family practices and 1078 patients with diagnosis of urinary incontinence (UI) for nurses compliance with evidence-linked review criteria for the assessment and management of UI and impact on psychologic and social well-being and symptoms. In the outreach arms, nurses' self-reported barriers informed development of tailored strategies.\n In comparison with educational materials alone, the implementation methods tested did not improve care at 6 months follow-up. Moderate rates of improvement (10-17% of patients) in performance for the assessment of UI and greater rates of improvement (20-30% of patients) for the management of care were found but effects were similar across arms. Improvement in patient outcomes was more consistently positive for educational outreach than for audit and feedback but differences were not significant. Adjustment for caseload size, severity or duration of UI and patients' age did not alter results.\n Printed educational materials alone may be as effective as audit and feedback and educational outreach in improving nurses' performance and outcomes of care for people with UI. Greater understanding of the underlying processes in improving performance within multidisciplinary teams through further, theory-driven studies with \"no intervention\" control groups and longer follow-up are needed.", "Meta-analyses show collaborative care models (CCMs) with nurse care management are effective for improving primary care for depression. This study aimed to develop CCM approaches that could be sustained and spread within Veterans Affairs (VA). Evidence-based quality improvement (EBQI) uses QI approaches within a research/clinical partnership to redesign care. The study used EBQI methods for CCM redesign, tested the effectiveness of the locally adapted model as implemented, and assessed the contextual factors shaping intervention effectiveness.\n The study intervention is EBQI as applied to CCM implementation. The study uses a cluster randomized design as a formative evaluation tool to test and improve the effectiveness of the redesign process, with seven intervention and three non-intervention VA primary care practices in five different states. The primary study outcome is patient antidepressant use. The context evaluation is descriptive and uses subgroup analysis. The primary context evaluation measure is naturalistic primary care clinician (PCC) predilection to adopt CCM.For the randomized evaluation, trained telephone research interviewers enrolled consecutive primary care patients with major depression in the evaluation, referred enrolled patients in intervention practices to the implemented CCM, and re-surveyed at seven months.\n Interviewers enrolled 288 CCM site and 258 non-CCM site patients. Enrolled intervention site patients were more likely to receive appropriate antidepressant care (66% versus 43%, p = 0.01), but showed no significant difference in symptom improvement compared to usual care. In terms of context, only 40% of enrolled patients received complete care management per protocol. PCC predilection to adopt CCM had substantial effects on patient participation, with patients belonging to early adopter clinicians completing adequate care manager follow-up significantly more often than patients of clinicians with low predilection to adopt CCM (74% versus 48%%, p = 0.003).\n Depression CCM designed and implemented by primary care practices using EBQI improved antidepressant initiation. Combining QI methods with a randomized evaluation proved challenging, but enabled new insights into the process of translating research-based CCM into practice. Future research on the effects of PCC attitudes and skills on CCM results, as well as on enhancing the link between improved antidepressant use and symptom outcomes, is needed.\n ClinicalTrials.gov: NCT00105820.", "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation." ]

[ "3904456", "2008006", "19517694", "16730113", "11914565", "7943103", "15913621", "10192481", "12706276", "1453405", "10023873", "8765270", "8141214", "1442910", "4050895" ]

[ "Prophylactic intrapartum amnioinfusion in patients with preterm premature rupture of membranes.", "A prospective, randomized evaluation of intrapartum amnioinfusion. Fetal acid-base status and cesarean delivery.", "Amnioinfusion for relief of recurrent severe and moderate variable decelerations in labor.", "Transcervical intrapartum amnioinfusion for preterm premature rupture of the membranes.", "Influence of volume preloading on uteroplacental and fetal circulation during spinal anaesthesia for caesarean section in uncomplicated singleton pregnancies.", "Prophylactic amnioinfusion for meconium-stained amniotic fluid.", "Therapeutic amnioinfusion for intrapartum fetal distress using a pediatric feeding tube.", "Amnioinfusion in term labor with low amniotic fluid due to rupture of membranes: a new indication.", "Prophylactic transcervical amnioinfusion in laboring women with oligohydramnios.", "Prophylactic intrapartum amnioinfusion for patients with oligohydramnios. A prospective randomized study.", "Intrapartum amnioinfusion in women with oligohydramniosis. A prospective randomized trial.", "Transabdominal amnioinfusion in oligohydramnios at term before induction of labor with intact membranes: a randomized clinical trial.", "Amnioinfusion during labor complicated by particulate meconium-stained amniotic fluid decreases neonatal morbidity.", "Prophylactic amnioinfusion improves outcome of pregnancy complicated by thick meconium and oligohydramnios.", "Saline amnioinfusion for relief of repetitive variable decelerations: a prospective randomized study." ]

[ "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.", "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.", "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.", "To investigate the effect of transcervical amnioinfusion on the management of labour and neonatal outcomes in preterm premature rupture of the membranes.\n This clinical trial included 86 patients with premature rupture of the membranes between weeks 27 and 35 of gestation. Patients were randomly assigned to receive amnioinfusion via a two-way catheter or to the control group. Clinical management was otherwise the same in both groups.\n Amnioinfusion decreased the frequency of variable decelerations in fetal heart rate (27.9% versus 53.5%, p<0.05) and the rate of obstetric interventions motivated by nonreassuring fetal status (13.6% versus 52.4%, p<0.05). At delivery, pH values were significantly higher in the treatment group than in the conventionally managed control group (median 7.29 versus 7.27).\n Intrapartum transcervical amnioinfusion for preterm premature rupture of the membranes reduced the number of interventions needed because of nonreassuring fetal status, and improved neonatal gasometric values without increasing maternal or fetal morbidity.", "Effects of volume preloading during spinal anaesthesia for elective caesarean section on maternal blood pressure, feto-maternal circulation and fetal outcome.\n In a pilot study a randomised trial was performed in 22 healthy women with uncomplicated, singleton pregnancies at 36-40 weeks of gestation undergoing elective caesarean section under spinal anaesthesia. In the low volume group (group A) patients received 150 ml of crystalloid solution for preloading, in the high volume group (group B) they were given 15 ml/kg of crystalloid solution for preloading before the initiation of spinal anaesthesia. Maternal blood pressure was monitored intermittently. Hypotension was defined as a decrease in systolic pressure to less than 80% of the baseline value. The Doppler flow evaluation consisted of measurements from the uterine artery at the placental site, fetal umbilical artery and fetal middle cerebral artery. Pulsatility indices were derived before and after fluid preloading, and when spinal anaesthesia was established. The neonatal outcome was assessed by Apgar scores, arterial acid base status and neurologic and adaptive capacity scores (NACS).\n The incidence of maternal hypotension in both groups was 45.5% (n = 10); 3 cases occurred in group A compared to 7 cases in group B (n.s.). There was no evidence that the high dose volume is useful in preventing maternal hypotension. The pulsatility indices of uterine arteries, umbilical arteries and middle cerebral arteries were not altered. Statistical analysis showed no changes in neonatal outcome concerning umbilical arterial pH, Apgar score and NACS (n.s.) between groups A and B.\n Our preliminary results suggest that high dose crystalloid volume preloading has no preventive function in the avoidance of maternal hypotension in healthy parturients undergoing elective caesarean section under spinal anaesthesia, and shows no harmful effects on neonatal outcome as long as maternal hypotension is corrected immediately. However, the statistical significance may reflect the small sample size, and larger series are needed before changing the current management.\n Copyright 2002 S. Karger AG, Basel", "Previous studies have demonstrated reduced perinatal morbidity in patients receiving amnioinfusion for meconium-stained amniotic fluid compared with control patients receiving no amnioinfusion. Because amnioinfusion for variable fetal heart rate decelerations has become accepted care, we sought to determine the benefit of prophylactic amnioinfusion for meconium compared with standard care, incorporating therapeutic amnioinfusion for variable decelerations.\n Ninety-three term patients with moderate to heavy meconium and no variable fetal heart rate decelerations were randomized to immediate prophylactic amnioinfusion (600 ml saline solution bolus followed by 3 ml/min) or to standard care (including therapeutic amnioinfusion for variable decelerations developing later). All babies had DeLee suctioning on delivery of the head. Laryngeal cords were visualized and tracheal suctioning performed when meconium was seen below the cords. Statistical comparisons were performed using Student t test, Fisher's exact test, or chi 2 analysis.\n There were no significant differences in the incidence of operative delivery, fetal distress, or meconium below the cords or in newborn Apgar scores and umbilical artery gas values between the amnioinfusion (n = 43) and control (n = 50) patients. There were four cases of meconium aspiration, three in the amnioinfusion group, one in the standard care group. The rate of endometritis-chorioamnionitis was higher (p = 0.3) in the amnioinfusion (16%) than in the control group (8%), although time from ruptured membranes to delivery (8.5 hours vs 7.3 hours) and duration of intrauterine monitoring (6.1 hours vs 5.3 hours) were not different.\n Although amnioinfusion does dilute amniotic meconium, prophylactic amnioinfusion for meconium in the absence of variable decelerations remains controversial. Prophylactic amnioinfusion in term pregnancies did not improve perinatal outcome and increased the risk for chorioamnionitis-endometritis. Together with recent reports, the current data suggest that the benefit of amnioinfusion for meconium-stained amniotic fluid is a result of the alleviation of variable fetal heart rate decelerations rather than meconium dilution.", "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.", "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.", "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.", "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.", "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.", "Our purpose was to evaluate the efficacy of prophylactic amnioinfusion in decreasing neonatal morbidity associated with labor complicated by particulate meconium-stained amniotic fluid and to assess potential complications of this procedure.\n One hundred five laboring pregnant women with particulate (moderate or thick) meconium by subjective clinical analysis were randomly assigned to receive amnioinfusion or to receive standard obstetric care without amnioinfusion. Patients with any antepartum complications, other than the presence of meconium, were excluded from the study. Statistical analyses consisted of the two-tailed and paired Student t tests, Pearson chi 2 test, and Wilcoxon nonparametric test. Significance was set at p < 0.05.\n The study included 47 patients in the study group and 58 patients in the control group. A significantly greater proportion of study patients demonstrated decreased meconium concentration between rupture of membranes and delivery (46 of 46 vs 15 of 58, p < 0.001). The relative dilution of meconium consistency by objective analysis was significantly different between the study group and the control group (77.1% decrease vs 9.3% increase, p < 0.001). The proportion of neonates with meconium below the vocal cords was reduced in the study group (two of 47 vs 36 of 58, p < 0.001). Umbilical artery pH was increased in the study group neonates (7.29 +/- 0.01 vs 7.25 +/- 0.009, p < 0.05). The rate of neonatal acidemia was reduced in the study group (4 of 45 vs 12 of 50, p < 0.05). The rate of meconium aspiration syndrome was reduced in the study group (1 of 47 vs 8 of 58, p < 0.05). Maternal and neonatal morbidity rates were similar.\n Prophylactic amnioinfusion should be considered a possible addition to the intrapartum management of patients with particulate meconium-stained amniotic fluid.", "The null hypothesis is that the use of intrapartum amnioinfusion in labors complicated by the presence of thick meconium and oligohydramnios will not decrease the incidence of fetal distress, cesarean delivery, meconium aspiration, or meconium aspiration syndrome.\n One hundred seventy term and postterm patients with thick meconium and oligohydramnios were randomly chosen to receive amnioinfusion or standard obstetric care without amnioinfusion. The frequency of fetal distress, cesarean section, meconium aspiration, and meconium aspiration syndrome were subject to chi 2 analysis, Student's t test, or Fisher's exact test.\n The rate of fetal distress was significantly reduced in the amnioinfusion group compared with controls (three of 85 vs 19 of 85, relative risk 0.15, 95% confidence interval 0.06 to 0.42). The rate of cesarean section for fetal distress was significantly reduced in the amnioinfusion group (two of 85 vs 17 of 85, relative risk 0.118, confidence interval 0.03 to 0.49). The rates of meconium aspiration (four of 85 vs 33 of 85, relative risk 0.12, confidence interval 0.0449 to 0.327) and meconium aspiration syndrome (0 of 85 vs five of 85, relative risk 0.09, confidence interval 0.009 to 0.872) were significantly reduced by amnioinfusion.\n Amnioinfusion improves the outcome in pregnancies complicated by thick meconium and oligohydramnios.", "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." ]

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

[ "[Total enteral nutrition vs. total parenteral nutrition in patients with severe acute pancreatitis].", "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.", "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.", "Early nasojejunal feeding in acute pancreatitis is associated with a lower complication rate.", "Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study.", "Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial." ]

[ "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.", "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.", "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.", "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.", "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.", "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." ]

[ "17045832", "16697231", "19951217", "17173219" ]

[ "Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis.", "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.", "Changes in the vaginal microenvironment with metronidazole treatment for bacterial vaginosis in early pregnancy.", "A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis." ]

[ "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.", "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 associated with preterm delivery, but there is little evidence that treatment improves pregnancy outcomes. We examined whether oral or vaginal metronidazole treatment for BV in early pregnancy was more effective in restoring the normal vaginal environment.\n This was a randomized controlled trial comparing oral and intravaginal metronidazole for treatment of BV in early pregnancy (<20 weeks). Vaginal samples collected at baseline and 4 weeks after treatment were evaluated using gram stain, culture, colorimetric detection of sialidase, and immunoassay for measurement of proinflammatory cytokines interleukins-1beta, -6, -8 (IL-1beta, IL-6, IL-8) and secretory leukocyte protease inhibitor (SLPI). We compared the effect of treatment between groups (using chi-square and t test) and within individuals (McNemar's test).\n Of 126 subjects, 108 (86%) completed follow-up (55 oral, 53 intravaginal). Of the study population, 34% achieved therapeutic cure, and this was not different between treatment groups. BV-associated bacteria were significantly reduced in both groups, but few subjects regained colonization with protective lactobacilli. Among women who achieved therapeutic cure, the level of IL-1beta dropped significantly (p < 0.001) and SLPI increased (p = 0.003). More women in the vaginal treatment group had undetectable sialidase after treatment (p = 0.013).\n Treatment with oral or intravaginal metronidazole in early pregnancy reduced colonization with BV-associated bacteria but was not effective in achieving therapeutic cure or in restoring healthy vaginal lactobacilli.", "Bacterial vaginosis (BV) is the most common cause of vaginitis worldwide. Currently recommended treatments have poor efficacy and are associated with high rates of BV recurrence. We examined whether a longer duration of treatment with metronidazole or combination therapy with metronidazole and azithromycin would enhance the cure rates for BV. In addition, we examined factors other than drug therapy associated with cure.\n Women with symptomatic BV (defined by a modified Amsel criteria) were enrolled in a 4-arm study that compared metronidazole for 7 days versus 14 days, plus or minus azithromycin on days 1 and 3. Data regarding interim behaviors were also obtained, as were vaginal specimens for Gram staining.\n At the first follow-up visit (7 days after the completion of therapy), there was a significant difference in cure rates among patients who received 7 days of metronidazole therapy, compared with those who received 14 days of therapy, combined across azithromycin therapy (P=.0003). There was no effect associated with azithromycin therapy. There were no differences in cure rates between any of the treatment groups at 21 days after completion of therapy. Abstinence or protected sex, refraining from douching, and a lower baseline Nugent score for the vaginal Gram stain were all significantly associated with cure.\n Cure rates for BV were significantly improved by 14 days of metronidazole treatment (compared with 7 days of treatment), but the effects were not sustained, suggesting that relapse or reinfection occurred. Combination therapy with the addition of azithromycin had no benefit. Lower baseline Nugent scores--presumably reflecting less complex vaginal flora--were significantly associated with cure, as was refraining from unprotected sex and from douching." ]

[ "10342710", "12428233", "16974191", "8849355", "16373258", "15989411", "15529389" ]

[ "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.", "Improvement of sustained attention and visual and movement skills, but not clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial.", "Dehydroepiandrosterone in systemic lupus erythematosus. Results of a double-blind, placebo-controlled, randomized clinical trial.", "Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus.", "Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids.", "The effect of dehydroepiandrosterone on lumbar spine bone mineral density in patients with quiescent systemic lupus erythematosus." ]

[ "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.", "Dehydroepiandrosterone (DHEA) augmentation has been reported, in a preliminary fashion, to be useful in the management of schizophrenia symptoms and side effects. In this study, the intention was to investigate the efficacy and safety of DHEA administration to ongoing antipsychotic medication in a multicenter, 12-week, double-blind, randomized, placebo-controlled, crossover trial.\n Fifty-five of 62 inpatients and outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia completed the trial. Patients were randomly allocated to 2 treatment groups receiving either DHEA (200 mg/d) or placebo for 6 weeks with the crossover between DHEA and placebo occurring after 6 weeks. Patients continued to receive their regular antipsychotic medication for the duration of the study.\n Compared with placebo, DHEA administration did not produce significant improvement in clinical symptoms, side effects, and quality-of-life scores. However, 6 weeks of DHEA administration (but not placebo) was associated with a significant improvement in Positive and Negative Symptom Scale ratings compared with baseline. Furthermore, 6 weeks of DHEA treatment was associated with significant improvement in cognitive functions of visual sustained attention and visual and movement skills compared with placebo conditions. The DHEA augmentation was associated with elevations of serum concentrations of both DHEA and its sulfate ester. The DHEA treatment was well tolerated without any serious adverse effects.\n This short-term study does not support DHEA's value as an effective adjunct in the treatment of symptoms, side effects, and quality-of-life impairment in schizophrenia, while suggesting that DHEA improves sustained attention and visual and movement skills. A long-term, large-scale study with a broader dose range is warranted to further investigate DHEA's role in the management of schizophrenia.", "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.", "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 the effects of combination estrogen/androgen therapy on muscle mass, strength and endurance, serum hormone and lipid profiles, and quality of life measures in postmenopausal women.\n Prospective, randomized, placebo-controlled pilot study at a tertiary care medical center. Fifty postmenopausal women were randomized to a 12-week course of (1) dehydroepiandrostenedione (DHEA) 50 mg daily, (2) conjugated equine estrogen (CEE) 0.625 mg daily, (3) DHEA 50 mg+CEE 0.625 mg daily, or (4) placebo. Main outcome measures of lower extremity muscle (calf) mass, functional muscle parameters, serum hormone and lipid levels, and quality of life (QOL) were obtained at baseline and after treatment. Statistical analysis compared percent change from baseline values and treatment differences among outcomes.\n Significant increases in mean DHEA, DHEA sulfate (DHEA-S), testosterone, and androstenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo. Compared with no hormone therapy, none of the supplemental hormone groups caused significant changes in muscle mass, muscle strength, muscle endurance, feelings of well-being, sleep, or sexual function.\n Androgen replacement therapy, with DHEA, to menopausal women increases serum androgen levels without any appreciable effect on muscle cross-sectional area, muscle strength, muscle function, or improvement in health-related QOL.", "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." ]

[ "15321573", "15177859", "7566849" ]

[ "Upright versus recumbent position in the second stage of labour in women with combined spinal-epidural analgesia.", "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.", "Randomized trial of epidural versus intravenous analgesia during labor." ]

[ "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.", "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.", "To compare the effects of epidural analgesia with intravenous (IV) analgesia on the outcome of labor.\n Thirteen hundred thirty women with uncomplicated term pregnancies and in spontaneous labor were randomized to be offered epidural bupivacaine-fentanyl or IV meperidine analgesia during labor.\n Comparison of the allocation groups by intent to treat revealed a significant association between epidural allocation and operative delivery for dystocia. However, only 65% of each randomization group accepted the allocated treatment. Four hundred thirty-seven women accepted and received meperidine as allocated, and they were compared with 432 women accepting epidural allocation. Significant associations resulted between epidural administration and prolongation of labor, increased rate of oxytocin administration, chorioamnionitis, low forceps, and cesarean delivery. Because of the high rate of noncompliance with treatment allocation, a multifactorial regression analysis was performed on the entire cohort, and a twofold relative risk of cesarean delivery persisted in association with epidural treatment. The impact of epidural treatment on cesarean delivery was significant for both nulliparous and parous women (risk ratios 2.55 and 3.81, respectively). Epidural analgesia provided significantly better pain relief in labor than did parenteral meperidine.\n Although labor epidural analgesia is superior to meperidine for pain relief, labor is prolonged, uterine infection is increased, and the number of operative deliveries are increased. A two- to fourfold increased risk of cesarean delivery is associated with epidural treatment in both nulliparous and parous women." ]

[ "11192954", "9926148", "10974183", "8620707", "9112877", "12953145", "10767227" ]

[ "Home-based exercise is capable of preserving hospital-based improvements in severe chronic obstructive pulmonary disease.", "Exercise training improves recovery in patients with COPD after an acute exacerbation.", "Short- and long-term effects of outpatient rehabilitation in patients with chronic obstructive pulmonary disease: a randomized 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.", "Hospital vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease.", "Long-term effects of a maintenance program after supervised or self-monitored training programs in patients with COPD.", "Long-term effects of outpatient rehabilitation of COPD: A randomized trial." ]

[ "We examined the feasibility of home-based walking training to maintain the benefits of a short-term exercise training in patients with severe chronic obstructive pulmonary disease (COPD). After initial recovery from an exacerbation, 46 patients were randomized into a training and a control group, and 30 patients completed the programme (mean +/- SD FEV1, 36 +/- 7% predicted). The training group performed a 10-day walking training programme in the hospital, followed by a 6-month programme of supervised walking training at home, integrated into daily activities. The control group did not have exercise training in the hospital or at home. Until 6 months after discharge, lung function, exercise performance and symptom scores were assessed. Six-minute walking distance in the training group improved from day 1 to day 10 (P<0.001) and this effect was maintained over 6 months (P<0.001). On average, daily walking distance at home was 2308 m and walking was reported on 157 days. Quality of life (QoL) scores changed significantly over 6 months (P<0.001). The control group showed no significant changes in exercise performance or QoL scores throughout the whole study period. Therefore, (i) significant improvements in exercise performance and Chronic Respiratory Disease Questionnaire (CRQ) scores could be achieved after recovery from an exacerbation and (ii) these improvements were maintained after discharge, when supported by a home-based walking training.", "Clinical experience suggests that exercise is beneficial for recovery after an acute exacerbation in patients with severe chronic obstructive pulmonary disease (COPD). The aim of this study was to quantify the clinical benefit of exercise in these patients. Twenty-nine inpatients were randomly assigned to a training group (n = 15, FEV1 34% pred) or a control group (n = 14, FEV1 38% pred). On ten consecutive days, patients in the training group performed a 6-min treadmill walking test and, in addition, five walking sessions per day at > or = 75% of the respective treadmill walking distance. Patients in the control group performed only treadmill walking tests on days 1, 5, and 10. To directly compare the possible benefit of exercise training all patients had an exercise test on day 11 at the same work load as on day 1. In the training group, 6-min walking distance increased from 237 to 420 m, in the control group from 230 to 255 m over the 10 day period which was significantly different (P < 0.0001). Minute ventilation and oxygen uptake increased significantly (P < 0.05) in the training but not in the control group. When comparing exercise tests on days 1 and 11, minute ventilation, oxygen uptake, PaCO2, lactic acid concentration, and Borg scale were significantly reduced to achieve the same work load (P < 0.01) only in the training group. Intrathoracic gas volume and residual volume decreased, and FEV1 and vital capacity increased in the training (P < 0.05) but not in the control group. Our data demonstrate that exercise training significantly improves the exercise capacity in patients with severe COPD after an acute exacerbation of their disease.", "Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease (COPD) in the short term, but their long-term effects are not known. We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD.\n One hundred patients were randomly assigned to receive either an exercise training program that included cycling, walking, and strength training (n = 50) or usual medical care (n = 50). Thirty-four patients in the training group were evaluated after 6 months (end of training), and 26 were evaluated after 18 months of follow-up. In the control group, 28 patients were evaluated at 6 months and 23 after 18 months. We measured pulmonary function, 6-minute walking distance, maximal exercise capacity, peripheral and respiratory muscle strength, and quality of life (on a 20 to 140-point scale), and estimated the cost-effectiveness of the program.\n At 6 months, the training group showed improvement in 6-minute walking distance [mean difference (training - control) of 52 m; 95% confidence interval (CI), 15 to 89 m], maximal work load (12 W; 95% CI, 6 to 19 W), maximal oxygen uptake (0.26 liters/min; 95% CI, 0.07 to 0.45 liters/min), quadriceps force (18 Nm; 95% CI, 7 to 29 Nm), inspiratory muscle force (11 cm H(2)O; 95% CI, 3 to 20 cm H(2)O), and quality of life (14 points; 95% CI, 6 to 21 points; all P <0.05). At 18 months all these differences persisted (P <0.05), except for inspiratory muscle strength. For 6-minute walking distance and quality of life, the differences between the training group and controls at 18 months exceeded the minimal clinically-important difference.\n Among patients who completed the 6-month program, outpatient training resulted in significant and clinically relevant changes in 6-minute walking distance, maximal exercise performance, peripheral and respiratory muscle strength, and quality of life. Most of these effects persisted 18 months after starting the program.", "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.", "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.", "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.", "To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea, exercise, health-related quality of life, and hospitalization rate.\n Secondary-care respiratory clinic in Barcelona.\n We conducted a randomized controlled trial with blinding of outcome assessment and follow-up at 3, 6, 9, 12, 18, and 24 months. Sixty patients with moderate to severe COPD (age 65 +/- 7 years; FEV(1) 35 +/- 14%) were recruited. Thirty patients randomized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy, 3 months of daily supervised exercise, and 6 months of weekly supervised breathing exercises. Thirty patients randomized to the control group received standard care.\n We found significant differences between groups in perception of dyspnea (p < 0.0001), in 6-min walking test distance (p < 0.0001), and in day-to-day dyspnea, fatigue, and emotional function measured by the Chronic Respiratory Questionnaire (p < 0. 01). The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up. The PR group experienced a significant (p < 0.0001) reduction in exacerbations, but not the number of hospitalizations. The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three.\n Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years." ]

[ "12145577", "16041208", "9449869", "19577251", "2039294", "1739177", "20232173", "18202889", "14607696", "16401473" ]

[ "Laparoscopic common bile duct exploration and cholecystectomy versus endoscopic stone extraction and laparoscopic cholecystectomy for choledocholithiasis. A prospective randomized study.", "Postoperative ERCP versus laparoscopic choledochotomy for clearance of selected bile duct calculi: a randomized trial.", "Randomised trial of laparoscopic exploration of common bile duct versus postoperative endoscopic retrograde cholangiography for common bile duct stones.", "Laparoscopic exploration of common bile duct with primary closure versus T-tube drainage: a randomized clinical trial.", "Choledocholithiasis. Endoscopic sphincterotomy or common bile duct exploration.", "Precholecystectomy endoscopic cholangiography and stone removal is not superior to cholecystectomy, cholangiography, and common duct exploration.", "Is the use of T-tube necessary after laparoscopic choledochotomy?", "A randomized comparison of primary closure and T-tube drainage of the common bile duct after laparoscopic choledochotomy.", "Duodenoscopy in treatment of acute gallstone pancreatitis.", "Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients." ]

[ "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.", "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.", "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.", "Traditionally, the common bile duct (CBD) is closed with T-tube drainage after choledochotomy and removal of CBD stones. However, the insertion of a T-tube is not without complication and the patients have to carry it for several weeks before removal. In the laparoscopic era, surgery is performed with minimally invasive techniques in order to reduce the trauma, hasten recovery, and reduce the hospital stay of patients. T-tube insertion seems to negate these benefits. This randomized study was designed to compare the two methods applied after LCBDE and to determine whether primary closure can be as safe as closure with T-tube drainage.\n From May 2000 to January 2008, 93 consecutive patients with common bile duct stones (CBDS) and gallbladder in situ were enrolled in this randomized study to undergo laparoscopic cholecystectomy with laparoscopic common bile duct exploration (LCBDE). Intraoperative findings, postoperative complications, postoperative stay, and hospital expenses were recorded and analyzed.\n There was no mortality in both groups. A T-tube was inserted in 46 patients and the CBD was closed primarily in 47. There were no differences in the demographic characteristics or clinical presentations between the two groups. Compared with the T-tube group, the operative time and postoperative stay were significantly shorter, the hospital expenses were significantly lower, and the incidences of overall postoperative complications and biliary complications were statistically and insignificantly lower in the primary closure group.\n LCBDE with primary closure without external drainage after laparoscopic choledochotomy is feasible and as safe as T-tube insertion.", "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.", "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.", "Traditionally, the common bile duct (CBD) is closed with T-tube drainage after choledochotomy and removal of CBD stones. However, the insertion of a T-tube is not without complication.\n This randomized study was designed to compare the use of T-tube and primary closure of choledochotomy after laparoscopic choledochotomy to determine whether primary closure can be as safe as closure with T-tube drainage.\n Between February 2006 and June 2009, 122 consecutive patients with proven choledocholithiasis had laparoscopic choledochotomy. They were randomized into two equal groups: T-tube (n = 61) and primary closure (n = 61). Demographic data, intraoperative findings, postoperative complications, and postoperative stay were recorded.\n There was no mortality in both groups. There were no differences in the demographic characteristics or clinical presentations between the two groups. Compared with the T-tube group, the operative time and postoperative stay were significantly shorter and the incidences of overall postoperative complications and biliary complications were statistically and significantly lower in the primary closure group.\n Laparoscopic common bile duct exploration with primary closure without external drainage after laparoscopic choledochotomy is feasible, safe, and cost-effective. After verification of ductal clearance, the CBD could be closed primarily without T-tube insertion.", "Traditionally, the common bile duct (CBD) has been closed with T-tube drainage after laparoscopic choledochotomy and removal of CBD stones. However, insertion of the T-tube is related to some potential postoperative complications, and patients must carry the T-tube for several weeks before its removal. Primary closure of the CBD without drainage has been proposed as a safe alternative to T-tube placement after laparoscopic choledochotomy. This randomized study aimed to compare the postoperative course and final outcome between the two methods applied after LCBDE.\n Between January 2000 and January 2004, 80 patients treated with laparoscopic choledochotomy for CBD stones were randomly assigned to primary duct closure (n = 40) or T-tube drainage (n = 40). The primary end points were morbidity, operative time, postoperative stay, hospital expenses, and time until return to work.\n There were no differences in the demographic characteristics or clinical presentations between the two groups. In the primary closure group, the postoperative stay (5.2 +/- 2.2 vs 8.3 +/- 3.6 days) and the time until return to work (12.6 +/- 5.1 vs 20.4 +/- 13.2 days) were significantly shorter, the hospital expenses (8,638 +/- 2,946 vs 12,531 +/- 4,352 yuan) were significantly lower, and the incidences of postoperative complications (15% vs 27.5%) and biliary complications (10% vs 20%) were statistically and insignificantly lower than in the T-tube drainage group. In the primary closure group, six patients experienced postoperative complications, four of whom had biliary complications, compared, respectively, with 11 and 8 patients in the T-tube drainage group.\n This study showed that primary CBC closure after laparoscopic choledochotomy was a viable alternative to mandatory T-tube drainage.", "To probe the potential use of duodenoscopy in the diagnosis and treatment of acute gallstone pancreatitis (GP).\n Fourty-five patients with acute GP were randomly divided into endoscopic retrograde cholangiopancreatography (ERCP) group (n=20) and non-ERCP group (n=25). Each group was subdivided into mild and severe groups according to APACHE II scores. They were given supportive treatment combined with traditional Chinese medicine. The patients in the ERCP group received ERCP within 24 hours after admission. If there were stones in the common bile duct with stenosis of the inferior extremity or ampulla, endoscopic sphincterotomy (ES) was performed to extract the stones by basket. If no calculi were identified or multiple stones were large, endoscopic naso-biliary drainage (ENBD) was carried out.\n The incidence of complication, length of hospitalization and cost were markedly lower in patients with severe acute GP in the ERCP group than those in the non-ERCP group (P<0.05), in contrast to the 2 mild subgroups of the ERCP and non-ERCP groups (P>0.05).\n It is feasible, effective and safe to apply duodenoscopy in the treatment of severe acute GP.", "In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ.\n We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes.\n One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12).\n In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended." ]

[ "8970221", "10072411", "10864055", "12447954", "9870832", "2658574" ]

[ "Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial.", "Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group.", "Use of amphotericin B colloidal dispersion in children.", "Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation.", "A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia.", "Empiric antifungal therapy in febrile granulocytopenic patients. EORTC International Antimicrobial Therapy Cooperative Group." ]

[ "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.", "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.", "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.", "Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation.\n Copyright 2002 Wiley-Liss, Inc.", "Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated.\n We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection.\n Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia.\n These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.", "The optimal management of fever in granulocytopenic patients remains controversial. Invasive fungal infections are common and life-threatening but are difficult to diagnose early. In this randomized study, we investigated the potential value of empiric administration of amphotericin B (versus no empiric antifungal therapy) in 132 patients remaining febrile and granulocytopenic despite broad-spectrum antibiotic therapy for four days.\n The patients were divided into two groups: 68 who were randomly assigned to receive empiric amphotericin B, and 64 who were randomly assigned to continue only the protocol antibiotics that they were already receiving. Amphotericin B was administered intravenously as follows: every other day at a dose of 1.2 mg/kg body weight or daily at a dose of 0.6 mg/kg body weight. Clinical response was evaluated as success or failure, depending upon the febrile course after randomization.\n Based on the evolution of fever, the response rate was 69% in the group of patients receiving empiric amphotericin B and 53% for the other group (p = 0.09). There were six documented (four severe) fungal infections in 64 patients randomized not to receive the antifungal therapy as compared to only one fungemia among 68 patients treated empirically with amphotericin B (p = 0.1). No deaths due to fungal infection occurred among the patients receiving empiric amphotericin B compared to four in the other group (p = 0.05). However, this study did not demonstrate a difference in survival between the two groups of patients (with or without empiric amphotericin B). The benefit of empiric administration of amphotericin B was primarily observed in specific subgroups of patients, such as those who did not receive any antifungal prophylaxis (78% versus 45%, p = 0.04), those who were severely granulocytopenic (69% versus 46%, p = 0.06), febrile patients with a clinically documented infection (75% versus 41%, p = 0.03), and patients older than 15 years of age (67% versus 47%, p = 0.06).\n These data suggest a benefit for early amphotericin B treatment in granulocytopenic patients with continued fever despite antibiotic therapy." ]

[ "16579803", "12173139", "20435345", "15699235", "1676467", "18595969", "8100345", "7901636", "10837300", "10037634", "16479521", "11488938", "11737959", "10465076", "11053508", "1353192" ]

[ "Randomised trial of vitamin A supplementation in pregnant women in rural Malawi found to be anaemic on screening by HemoCue.", "Antenatal vitamin A supplementation increases birth weight and decreases anemia among infants born to human immunodeficiency virus-infected women in Malawi.", "Effect of vitamin A supplementation in women of reproductive age on maternal survival in Ghana (ObaapaVitA): a cluster-randomised, placebo-controlled trial.", "Effect of postpartum maternal or neonatal vitamin A supplementation on infant mortality among infants born to HIV-negative mothers in Zimbabwe.", "Efficacy of vitamin A in reducing preschool child mortality in Nepal.", "Newborn vitamin A supplementation reduced infant mortality in rural Bangladesh.", "Vitamin A supplementation in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality. Ghana VAST Study Team.", "Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia.", "Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal.", "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.", "Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality.", "Impact of vitamin A supplementation on anaemia and plasma erythropoietin concentrations in pregnant women: a controlled clinical trial.", "Vitamin A and iron supplementation of Indonesian pregnant women benefits vitamin A status of their infants.", "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.", "Supplemental vitamin A improves anemia and growth in anemic school children in Tanzania.", "Vitamin A supplementation and child survival." ]

[ "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.", "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.", "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.", "Young infants are at risk of vitamin A deficiency. Supplementation of breastfeeding mothers improves the vitamin A status of their infants, but there are no data regarding its effect on infant mortality, and data on the effect of directly supplementing infants during the first few weeks of life are conflicting.\n The objective was to measure the effect on infant mortality of supplementing neonates and their HIV-negative mothers with single, large doses of vitamin A during the immediate postpartum period.\n A randomized, placebo-controlled, 2-by-2 factorial design trial was conducted in 14,110 mothers and their infants; 9208 of the mothers were HIV-negative at delivery, remained such during the postpartum year, and were retained in the current analysis. The infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A (Aa), mothers received vitamin A and infants received placebo (Ap), mothers received placebo and infants received vitamin A (Pa), and both mothers and infants received placebo (Pp). The vitamin A dose in the mothers was 400,000 IU and in the infants was 50,000 IU. The mother-infant pairs were followed to 12 mo.\n Hazard ratios (95% CI) for 12 mo mortality among infants in the maternal-supplemented and infant-supplemented groups were 1.17 (0.87, 1.58) and 1.08 (0.80, 1.46), respectively. Hazard ratios (95% CI) for the Aa, Ap, and Pa groups compared with the Pp group were 1.28 (0.83, 1.98), 1.27 (0.82, 1.97), and 1.18 (0.76, 1.83), respectively. These data indicate no overall effect. Serum retinol concentrations among a subsample of women were similar to reference norms.\n Postpartum maternal or neonatal vitamin A supplementation may not reduce infant mortality in infants of HIV-negative women with an apparently adequate vitamin A status.", "Community trials of the efficacy of vitamin A supplementation in reducing preschool childhood mortality have produced conflicting results. To resolve the question, a randomised, double-masked, placebo-controlled community trial of 28,630 children aged 6-72 months was carried out in rural Nepal, an area representative of the Gangetic flood plain of South Asia. Randomisation was carried out by administrative ward; the vitamin-A-supplemented children received 60,000 retinol equivalents every 4 months and placebo-treated children received identical capsules containing 300 retinol equivalents. After 12 months, the relative risk of death in the vitamin-A-supplemented compared with the control group was 0.70 (95% confidence interval 0.56-0.88), equivalent to a 30% reduction in mortality. The trial, which had been planned to last 2 years, was discontinued. The reduction in mortality was present in both sexes (relative risk for boys 0.77; for girls 0.65), at all ages (range of relative risks 0.83-0.50), and throughout the year (0.76-0.67). The reduction in mortality risk was not affected by acute nutritional status, as measured by arm circumference. Thus, periodic vitamin A delivery in the community can greatly reduce child mortality in developing countries.", "We assessed the effect of supplementing newborns with 50000 IU of vitamin A on all-cause infant mortality through 24 weeks of age.\n This was a community-based, double-masked, cluster-randomized, placebo-controlled trial conducted in 19 unions in rural northwest Bangladesh. The study was nested into and balanced across treatment arms of an ongoing placebo-controlled, weekly maternal vitamin A or beta-carotene supplementation trial. Study-defined sectors (N = 596) were evenly randomized for newborns of participating mothers to receive a single, oral supplement of vitamin A (50000 IU) or placebo as droplets of oil squeezed from a gelatinous capsule. Mothers provided informed consent for newborn participation at approximately 28 weeks' gestation. After birth, typically at home (where >90% of births occurred), infants were supplemented and their vital status was followed through 24 weeks of age. The main outcome measure was mortality through 24 weeks of age.\n We obtained maternal consent to dose 17116 live-born infants (99.8% of all eligible) among whom 15937 (93.1%) were visited to be supplemented <30 days after birth and for whom vital status at 24 weeks of age was known. Dosed infants (n = 15902 [99.8%]) received their study supplement at a median age of 7 hours. Relative to control subjects, the risk of death in vitamin A-supplemented infants was 0.85, reflecting a 15% reduction in all-cause mortality. Protective relative risks were indistinguishable by infant gender, gestational age, birth weight, age at dosing, maternal age, parity, or across the 3 treatment arms of the maternal supplementation trial.\n Newborn vitamin A dosing improved infant survival through the first 6 months of life in Bangladesh. These results corroborate previous findings from studies in Indonesia and India and provide additional evidence that vitamin A supplementation shortly after birth can reduce infant mortality in South Asia.", "Although most studies on the effect of vitamin A supplementation have reported reductions in childhood mortality, the effects on morbidity are less clear. We have carried out two double-blind, randomised, placebo-controlled trials of vitamin A supplementation in adjacent populations in northern Ghana to assess the impact on childhood morbidity and mortality. The Survival Study included 21,906 children aged 6-90 months in 185 geographical clusters, who were followed for up to 26 months. The Health Study included 1455 children aged 6-59 months, who were monitored weekly for a year. Children were randomly assigned either 200,000 IU retinol equivalent (100,000 IU under 12 months) or placebo every 4 months; randomisation was by individual in the Health Study and by cluster in the Survival Study. There were no significant differences in the Health Study between the vitamin A and placebo groups in the prevalence of diarrhoea or acute respiratory infections; of the symptoms and conditions specifically asked about, only vomiting and anorexia were significantly less frequent in the supplemented children. Vitamin-A-supplemented children had significantly fewer attendances at clinics (rate ratio 0.88 [95% CI 0.81-0.95], p = 0.001), hospital admissions (0.62 [0.42-0.93], p = 0.02), and deaths (0.81 [0.68-0.98], p = 0.03) than children who received placebo. The extent of the effect on morbidity and mortality did not vary significantly with age or sex. However, the mortality rate due to acute gastroenteritis was lower in vitamin-A-supplemented than in placebo clusters (0.66 [0.47-0.92], p = 0.02); mortality rates for all other causes except acute lower respiratory infections and malaria were also lower in vitamin A clusters, but not significantly so. Improving the vitamin A intake of young children in populations where xerophthalmia exists, even at relatively low prevalence, should be a high priority for health and agricultural services in Africa and elsewhere.", "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.", "The effect of vitamin A supplementation on the survival of infants aged <6 mo is unclear. Because most infant deaths occur in the first few month of life, maternal supplementation may improve infant survival.\n The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants <6 mo of age.\n Married women of reproductive age in 270 wards of Sarlahi district, Nepal, were eligible to participate. Wards were randomly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate (vitamin A), 42 mg all-trans-beta-carotene, or placebo. Pregnancies were followed until miscarriage, stillbirth, maternal death, or live birth of one or more infants, who were followed through 24 wk of age.\n A total of 43559 women were enrolled; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial. The rate of fetal loss was 92.0/1000 pregnancies in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.06 (95% CI: 0.91, 1.25) and 1.03 (95% CI: 0.87, 1.19), respectively. The 24-wk mortality rate was 70.8/1000 live births in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.05 (95% CI: 0.87, 1.25) and 1.03 (95% CI: 0.86, 1.22), respectively.\n Small weekly doses of vitamin A or beta-carotene given to women before conception, during pregnancy, and through 24 wk postpartum did not improve fetal or early infant survival in Nepal.", "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.", "Low maternal serum retinol level is a risk factor for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality. The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency; neonatal dosing is under consideration. We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT, HIV-free survival, and mortality in HIV-exposed infants.\n A total of 14,110 mother-infant pairs were enrolled < or =96 h after delivery, and both mother and infant, mother only, infant only, or neither received vitamin A supplementation in a randomized, placebo-controlled trial with a 2 x 2 factorial design. All but 4 mothers initiated breast-feeding. A total of 4495 infants born to HIV-positive women were included in the present analysis.\n Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months. However, the timing of infant HIV infection modified the effect that supplementation had on mortality. Vitamin A supplementation had no effect in infants who were polymerase chain reaction (PCR) positive [corrected] for HIV at baseline. In infants who were PCR negative at baseline and PCR positive at 6 weeks, neonatal supplementation reduced mortality by 28% (P=.01), but maternal supplementation had no effect. In infants who were PCR negative at 6 weeks, all 3 vitamin A regimens were associated with ~2-fold higher mortality (P< or =.05).\n Targeted vitamin A supplementation of HIV-positive children prolongs their survival. However, postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks. These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas.", "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.", "Many Indonesian infants have an inadequate nutritional status, which may be due in part to inadequate maternal nutrition during pregnancy. This study was designed to investigate whether infant nutritional status could be improved by maternal vitamin A and Fe supplementation during gestation. Mothers of these infants from five villages had been randomly assigned on an individual basis, supervised and double-blind, to receive supplementation once weekly from approximately 18 weeks of pregnancy until delivery. Supplementation comprised 120 mg Fe and 500 microg folic acid with or without 4800 retinol equivalent vitamin A. Mothers of infants from four other villages who participated in the national Fe and folic acid supplementation programme were also recruited; intake of tablets was not supervised. Anthropometric and biochemical parameters of infants and their mothers were assessed approximately 4 months after delivery. Infants of mothers supplemented with vitamin A plus Fe had higher serum retinol concentrations than infants of mothers supplemented with Fe alone. However, the proportion of infants with serum retinol concentrations <0.70 micromol/l was >70 % in all groups. Maternal and infant serum retinol concentrations were correlated. Fe status, weight and length of infants were similar in all groups. Fe status of girls was better than that of boys, but boys were heavier and longer. We conclude that supplementation with vitamin A in conjunction with Fe supplementation of women during pregnancy benefits vitamin A status of their infants. However, considering the large proportion of infants with marginal serum retinol concentrations, it may still be necessary to increase their vitamin A intake.", "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.", "We conducted a randomized controlled trial of the effects of dietary supplements on anemia, weight and height in 136 anemic school children from a low socioeconomic background in Bagamoyo District schools in Tanzania. The aim of the current study was to investigate the impact of dietary supplements on anemia and anthropometric indices of anemic school children. The supplements were vitamin A alone, iron and vitamin A, iron alone or placebo, administered in a double-blinded design for 3 mo. All supplements were provided with local corn meals. Hemoglobin concentration, body weight and height were measured at baseline and at follow-up after supplementation. Vitamin A supplementation increased the mean hemoglobin concentration by 13.5 g/L compared with 3.5 g/L for placebo [P < 0.0001, 95% confidence interval (CI) 6.19-13.57), the mean body weight by 0.6 kg compared with 0.2 kg for placebo (P < 0.0001, 95% CI 0.19-0.65) and the mean height by 0.4 cm compared with 0.1 cm for placebo (P = 0.0009, 95% CI 0.08-0.42). However, the group of children who received combined vitamin A and iron supplementation had the greatest improvements in all indicators compared with placebo (18.5 g/L, P < 0.0001, 95% CI 14.81-22.23; 0.7 kg, P < 0. 0001, 95% CI 0.43-0.88 and 0.4 cm, P < 0.0001, 95% CI 0.22-0.56 for hemoglobin, weight and height, respectively). It is likely that vitamin A supplementation may have a useful role in combating the problems of vitamin A deficiency and anemia, as well as in improving children's growth, in developing countries.", "Previous studies of the effect of 6-monthly vitamin A supplementation on child mortality have given conflicting results. In other trials, more frequent doses of vitamin A have significantly reduced mortality among children at risk of vitamin A deficiency. We have done a double-blind, placebo-controlled trial of vitamin A supplementation in the Sudan among 28,753 children aged 9-72 months at risk of vitamin A deficiency. Children were assigned to receive either 200,000 IU vitamin A and 40 IU vitamin E every 6 months (vitamin A group) or 40 IU vitamin E alone (placebo group). During the 18 months of follow-up, there were 120 deaths (8.4/1000) in the vitamin A group and 112 (7.9/1000) in the placebo group (relative risk 1.06, 95% confidence interval 0.82-1.37). Controlling for geographic site, round of observation, anthropometry, morbidity, dietary intake of vitamin A, sex, and all baseline differences between the two groups did not change the results. Children living in poor and unsanitary environments, younger children, and those sick, stunted, wasted, or consuming diets low in vitamin A were at a significantly higher risk of dying. The lack of an effect of large-dose vitamin A supplementation on mortality, despite a clear association between dietary vitamin A and mortality, underscores the need to identify factors that modify the efficacy of vitamin A supplements as a public-health measure. Reducing poverty, improvements in sanitation, and access to adequate diets should remain the main goals to improve child survival." ]

[ "19572992" ]

[ "Management of bronchiolitis without antibiotics: a multicentre randomized control trial in Bangladesh." ]

[ "To ascertain that antibiotics have no role in the management of bronchiolitis.\n Multicentre randomized control trial (RCT).\n Five purposively selected teaching hospitals in Bangladesh.\n Children under 24 months old with bronchiolitis.\n Children were randomized into three groups of therapeutic interventions: parenteral ampicillin (P-Ab), oral erythromycin (O-Ab) and no antibiotic (N-Ab) in adjunct to supportive measures.\n Clinical improvement was assessed using 18 symptoms/signs which were graded on a two-point recovery scale of 'rapid' and 'gradual', indicating improvement within 'four days' and 'beyond four days', respectively.\n Each intervention group consisted of 98 +/- 1 children having comparable clinico-epidemiological characteristics at the baseline. The trial revealed that most chesty features (features appearing to arise from chest, i.e. cough, breathing difficulty, wheeze, chest indrawing, tachypnoea, tachycardia, rhonchi and crepitation) demonstrated a gradual recovery, beyond 4th admission day and, not differing among the three intervention groups (p > 0.23, p < 0.62, p = 0.54, p < 0.27, p = 0.75, p = 0.76, p = 0.81, p > 0.98, respectively). Most non-chesty features (features appearing to arise away from chest, i.e. feeding/sleeping difficulties, social smile, restlessness, inconsolable crying, nasal flaring, fever and hypoxaemia) demonstrated a rapid recovery, within 4 days, remaining comparable among the three intervention groups (p < 0.07, p = 0.65, p = 0.24, p < 0.61, p = 0.22, p = 0.84, p = 0.29 and p = 0.96, respectively). However, nasal symptoms (runny nose and nasal blockage) also showed no difference among groups (p = 0.36 and p = 0.66, respectively). Thus, the dynamics of clinical outcome obviates that children not receiving antibiotics had similar clinical outcome than those who did.\n In hospital settings, managing bronchiolitis with only supportive measures but without antibiotics remains preferable." ]

[ "3511372", "2189149", "16773409", "11752031" ]

[ "Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs.", "The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party.", "Effect of fosinopril in children with steroid-resistant idiopathic nephrotic syndrome.", "Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy." ]

[ "We evaluated renal function in 107 patients with active lupus nephritis who participated in long-term randomized therapeutic trials (median follow-up, seven years). For patients taking oral prednisone alone, the probability of renal failure began to increase substantially after five years of observation. Renal function was better preserved in patients who received various cytotoxic-drug therapies, but the difference was statistically significant only for intravenous cyclophosphamide plus low-dose prednisone as compared with high-dose prednisone alone (P = 0.027). The advantage of treatment with intravenous cyclophosphamide over oral prednisone alone was particularly apparent in the high-risk subgroup of patients who had chronic histologic changes on renal biopsy at study entry. Patients treated with intravenous cyclophosphamide have not experienced hemorrhagic cystitis, cancer, or a disproportionate number of major infections. We conclude that, as compared with high-dose oral prednisone alone, treatment of lupus glomerulonephritis with intravenous cyclophosphamide reduces the risk of end-stage renal failure with few serious complications.", "We have assessed the medium-term effect of a short course of high-dose, alternate-day prednisolone on adult nephrotic patients with membranous nephropathy, using a randomized, prospective, double-blind, controlled trial. Patients were entered over the period 1981 to 1984 and were observed for a minimum of three years. One hundred and seven adult patients who had not previously received immunosuppressive treatment were included in the trial. One hundred and sixty further patients, excluded from the trial, but with membranous nephropathy were identified, followed and assessed retrospectively at the end of the trial. At 36 months there was no significant difference between control and treatment groups in plasma creatinine, creatinine clearance or 24-h excretion of protein. At between three and six months serum albumin concentrations were higher and protein excretions lower in the treatment group compared to controls. No significant benefit was therefore observed on renal function in the medium term.", "We aimed to test if fosinopril reduces urinary protein excretion and alleviates renal tubular damage in normotensive children with steroid-resistant idiopathic nephrotic syndrome (SRINS). We also aimed to evaluate whether there are changes in steady-state blood pressure and serum concentrations of serum angiotensin-converting enzyme (ACE) and plasma renin activity or angiotensin II (AT-II) in children under this treatment. Forty-five normotensive patients with SRINS were randomly divided into two groups. Group I was treated with fosinopril and prednisone for 12 weeks, while group II was treated with prednisone alone for the same duration. The values of 24-h urinary protein excretion were 1.25+/-0.64 vs 2.52+/-0.56 g/24 h (P<0.05), 1.16+/-0.45 vs 2.42+/-0.24 g/24 h (P<0.05), and 1.10+/-0.41 vs 2.05+/-0.46 g/24 h (P<0.05) in group I and group II patients, respectively, at 4, 8, and 12 weeks. Patients in group I showed lower serum concentrations of urinary retinol-binding protein and beta(2)-microglobulin (P<0.01) at the end of the study, but the patients' blood pressure and components of the renin-angiotensin system (RAS) had no change during treatment. The result suggested that fosinopril significantly reduced proteinuria and alleviated renal tubular damage, but did not influence blood pressure and components of systemic RAS in normotensive children with SRINS.", "In a single-center, multiple-referral source study, 38 patients with progressive IgA nephropathy and controlled hypertension were randomized to treatment with prednisolone and cytotoxic agents, to therapy with low-dose cyclophosphamide then azathioprine, and to control groups. The follow-up period lasted 2 to 6 yr. Renal survival, as assessed by Kaplan-Meier analysis annually to 5 yr, showed significant preservation of function from 3 yr in the treatment group and 82, 82, 72, and 72% for 2, 3, 4, and 5 yr, respectively, compared with 68, 47, 26, and 6% in controls. Rate of loss of renal function, evaluated objectively by least-squares analyses of reciprocal serum creatinine, was reduced-and in one-third of the patients, arrested-during immunosuppressive treatment. Proteinuria, present in all patients at the time of entry into the trial, was reduced by treatment from 12 mo, compared with pretreatment levels or controls; erythrocyturia was reduced from 6 mo. Histologic activity and chronicity indexes were determined in renal biopsies performed at trial entry. Multivariate analysis demonstrated that mesangial cell proliferation and matrix scores were highest in those patients with more rapidly progressive disease. No morphologic variable or residual renal function predicted response to immunosuppressive therapy at entry. Mean arterial pressures did not differ significantly between treatment and control groups. There was thus no explanation other than treatment for the improved outcome in patients who received immunosuppressive therapy. Morbidity attributable to treatment or to renal failure occurred in both groups; an audit showed that benefits of therapy outweighed expected or minor side effects of drugs in this population at risk of end-stage renal failure. Patients selected for moderately progressive IgA nephropathy benefit from treatment with prednisolone and cytotoxic agents; results are consistent with modulation of systemic immune response or nephritic injury, thus explaining improved outcome, and indicate that this therapy has an acceptably low risk of side effects." ]